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id="toc-Obsessive–compulsive_disorder" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Obsessive–compulsive_disorder"> <div class="vector-toc-text"> 1.2.3 Obsessive–compulsive disorder </div> </a> <ul id="toc-Obsessive–compulsive_disorder-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Post–traumatic_stress_disorder" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Post–traumatic_stress_disorder"> <div class="vector-toc-text"> 1.2.4 Post–traumatic stress disorder </div> </a> <ul id="toc-Post–traumatic_stress_disorder-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Panic_disorder" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Panic_disorder"> <div class="vector-toc-text"> 1.2.5 Panic disorder </div> </a> <ul id="toc-Panic_disorder-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Eating_disorders" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Eating_disorders"> <div class="vector-toc-text"> 1.3 Eating disorders </div> </a> <ul id="toc-Eating_disorders-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Pain" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Pain"> <div class="vector-toc-text"> 1.4 Pain </div> </a> <ul id="toc-Pain-sublist" class="vector-toc-list"> <li id="toc-Fibromyalgia" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Fibromyalgia"> <div class="vector-toc-text"> 1.4.1 Fibromyalgia </div> </a> <ul id="toc-Fibromyalgia-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Neuropathic_pain" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Neuropathic_pain"> <div class="vector-toc-text"> 1.4.2 Neuropathic pain </div> </a> <ul id="toc-Neuropathic_pain-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Other_uses" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Other_uses"> <div class="vector-toc-text"> 1.5 Other uses </div> </a> <ul id="toc-Other_uses-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Limitations_and_strategies" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Limitations_and_strategies"> <div class="vector-toc-text"> 1.6 Limitations and strategies </div> </a> <ul id="toc-Limitations_and_strategies-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Switching_antidepressants" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Switching_antidepressants"> <div class="vector-toc-text"> 1.7 Switching antidepressants </div> </a> <ul id="toc-Switching_antidepressants-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Augmentation_and_combination" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Augmentation_and_combination"> <div class="vector-toc-text"> 1.8 Augmentation and combination </div> </a> <ul id="toc-Augmentation_and_combination-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Long-term_use_and_stopping" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Long-term_use_and_stopping"> <div class="vector-toc-text"> 1.9 Long-term use and stopping </div> </a> <ul id="toc-Long-term_use_and_stopping-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Adverse_effects" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Adverse_effects"> <div class="vector-toc-text"> 2 Adverse effects </div> </a> <button aria-controls="toc-Adverse_effects-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> Toggle Adverse effects subsection </button> <ul id="toc-Adverse_effects-sublist" class="vector-toc-list"> <li id="toc-Pregnancy" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Pregnancy"> <div class="vector-toc-text"> 2.1 Pregnancy </div> </a> <ul id="toc-Pregnancy-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Antidepressant-induced_mania" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Antidepressant-induced_mania"> <div class="vector-toc-text"> 2.2 Antidepressant-induced mania </div> </a> <ul id="toc-Antidepressant-induced_mania-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Suicide" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Suicide"> <div class="vector-toc-text"> 2.3 Suicide </div> </a> <ul id="toc-Suicide-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Sexual_dysfunction" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Sexual_dysfunction"> <div class="vector-toc-text"> 2.4 Sexual dysfunction </div> </a> <ul id="toc-Sexual_dysfunction-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Emotional_blunting" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Emotional_blunting"> <div class="vector-toc-text"> 2.5 Emotional blunting </div> </a> <ul id="toc-Emotional_blunting-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Changes_in_weight" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Changes_in_weight"> <div class="vector-toc-text"> 2.6 Changes in weight </div> </a> <ul id="toc-Changes_in_weight-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Bone_loss" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Bone_loss"> <div class="vector-toc-text"> 2.7 Bone loss </div> </a> <ul id="toc-Bone_loss-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Risk_of_death" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Risk_of_death"> <div class="vector-toc-text"> 2.8 Risk of death </div> </a> <ul id="toc-Risk_of_death-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Discontinuation_syndrome" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Discontinuation_syndrome"> <div class="vector-toc-text"> 2.9 Discontinuation syndrome </div> </a> <ul id="toc-Discontinuation_syndrome-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Pharmacology" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Pharmacology"> <div class="vector-toc-text"> 3 Pharmacology </div> </a> <ul id="toc-Pharmacology-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Types" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Types"> <div class="vector-toc-text"> 4 Types </div> </a> <button aria-controls="toc-Types-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> Toggle Types subsection </button> <ul id="toc-Types-sublist" class="vector-toc-list"> <li id="toc-Selective_serotonin_reuptake_inhibitors" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Selective_serotonin_reuptake_inhibitors"> <div class="vector-toc-text"> 4.1 Selective serotonin reuptake inhibitors </div> </a> <ul id="toc-Selective_serotonin_reuptake_inhibitors-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Serotonin–norepinephrine_reuptake_inhibitors" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Serotonin–norepinephrine_reuptake_inhibitors"> <div class="vector-toc-text"> 4.2 Serotonin–norepinephrine reuptake inhibitors </div> </a> <ul id="toc-Serotonin–norepinephrine_reuptake_inhibitors-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Serotonin_modulators_and_stimulators" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Serotonin_modulators_and_stimulators"> <div class="vector-toc-text"> 4.3 Serotonin modulators and stimulators </div> </a> <ul id="toc-Serotonin_modulators_and_stimulators-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Serotonin_antagonists_and_reuptake_inhibitors" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Serotonin_antagonists_and_reuptake_inhibitors"> <div class="vector-toc-text"> 4.4 Serotonin antagonists and reuptake inhibitors </div> </a> <ul id="toc-Serotonin_antagonists_and_reuptake_inhibitors-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Tricyclic_antidepressants" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Tricyclic_antidepressants"> <div class="vector-toc-text"> 4.5 Tricyclic antidepressants </div> </a> <ul id="toc-Tricyclic_antidepressants-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Tetracyclic_antidepressants" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Tetracyclic_antidepressants"> <div class="vector-toc-text"> 4.6 Tetracyclic antidepressants </div> </a> <ul id="toc-Tetracyclic_antidepressants-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Monoamine_oxidase_inhibitors" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Monoamine_oxidase_inhibitors"> <div class="vector-toc-text"> 4.7 Monoamine oxidase inhibitors </div> </a> <ul id="toc-Monoamine_oxidase_inhibitors-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-NMDA_receptor_antagonists" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#NMDA_receptor_antagonists"> <div class="vector-toc-text"> 4.8 NMDA receptor antagonists </div> </a> <ul id="toc-NMDA_receptor_antagonists-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Others" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Others"> <div class="vector-toc-text"> 4.9 Others </div> </a> <ul id="toc-Others-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Adjuncts" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Adjuncts"> <div class="vector-toc-text"> 5 Adjuncts </div> </a> <button aria-controls="toc-Adjuncts-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> Toggle Adjuncts subsection </button> <ul id="toc-Adjuncts-sublist" class="vector-toc-list"> <li id="toc-Less_common_adjuncts" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Less_common_adjuncts"> <div class="vector-toc-text"> 5.1 Less common adjuncts </div> </a> <ul id="toc-Less_common_adjuncts-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-History" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#History"> <div class="vector-toc-text"> 6 History </div> </a> <button aria-controls="toc-History-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> Toggle History subsection </button> <ul id="toc-History-sublist" class="vector-toc-list"> <li id="toc-Isoniazid,_iproniazid,_and_imipramine" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Isoniazid,_iproniazid,_and_imipramine"> <div class="vector-toc-text"> 6.1 Isoniazid, iproniazid, and imipramine </div> </a> <ul id="toc-Isoniazid,_iproniazid,_and_imipramine-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Second-generation_antidepressants" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Second-generation_antidepressants"> <div class="vector-toc-text"> 6.2 Second-generation antidepressants </div> </a> <ul id="toc-Second-generation_antidepressants-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Rapid-acting_antidepressants" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Rapid-acting_antidepressants"> <div class="vector-toc-text"> 6.3 Rapid-acting antidepressants </div> </a> <ul id="toc-Rapid-acting_antidepressants-sublist" class="vector-toc-list"> <li id="toc-Research" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Research"> <div class="vector-toc-text"> 6.3.1 Research </div> </a> <ul id="toc-Research-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Publication_bias_and_aged_research" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Publication_bias_and_aged_research"> <div class="vector-toc-text"> 6.4 Publication bias and aged research </div> </a> <ul id="toc-Publication_bias_and_aged_research-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Society_and_culture" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Society_and_culture"> <div class="vector-toc-text"> 7 Society and culture </div> </a> <button aria-controls="toc-Society_and_culture-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> Toggle Society and culture subsection </button> <ul id="toc-Society_and_culture-sublist" class="vector-toc-list"> <li id="toc-Prescription_trends" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Prescription_trends"> <div class="vector-toc-text"> 7.1 Prescription trends </div> </a> <ul id="toc-Prescription_trends-sublist" class="vector-toc-list"> <li id="toc-United_Kingdom" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#United_Kingdom"> <div class="vector-toc-text"> 7.1.1 United Kingdom </div> </a> <ul id="toc-United_Kingdom-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-United_States" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#United_States"> <div class="vector-toc-text"> 7.1.2 United States </div> </a> <ul id="toc-United_States-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Adherence" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Adherence"> <div class="vector-toc-text"> 7.2 Adherence </div> </a> <ul id="toc-Adherence-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Social_science_perspective" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Social_science_perspective"> <div class="vector-toc-text"> 7.3 Social science perspective </div> </a> <ul id="toc-Social_science_perspective-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Environmental_impacts" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Environmental_impacts"> <div class="vector-toc-text"> 7.4 Environmental impacts </div> </a> <ul id="toc-Environmental_impacts-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-See_also" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#See_also"> <div class="vector-toc-text"> 8 See also </div> </a> <ul id="toc-See_also-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-References" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#References"> <div class="vector-toc-text"> 9 References </div> </a> <ul id="toc-References-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Further_reading" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Further_reading"> <div class="vector-toc-text"> 10 Further reading </div> </a> <ul id="toc-Further_reading-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-External_links" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#External_links"> <div class="vector-toc-text"> 11 External links </div> </a> <ul id="toc-External_links-sublist" class="vector-toc-list"> </ul> </li> </ul> </div> </div> </nav> </div> </div> <div class="mw-content-container"> <main id="content" class="mw-body"> <header class="mw-body-header vector-page-titlebar"> <nav aria-label="Contents" class="vector-toc-landmark"> <div id="vector-page-titlebar-toc" class="vector-dropdown vector-page-titlebar-toc vector-button-flush-left" title="Table of Contents" > <input type="checkbox" id="vector-page-titlebar-toc-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-vector-page-titlebar-toc" class="vector-dropdown-checkbox " aria-label="Toggle the table of contents" > <label id="vector-page-titlebar-toc-label" for="vector-page-titlebar-toc-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--icon-only " aria-hidden="true" > Toggle the table of contents </label> <div class="vector-dropdown-content"> <div id="vector-page-titlebar-toc-unpinned-container" class="vector-unpinned-container"> </div> </div> </div> </nav> <h1 id="firstHeading" class="firstHeading mw-first-heading">Antidepressant</h1> <div id="p-lang-btn" class="vector-dropdown mw-portlet mw-portlet-lang" > <input type="checkbox" id="p-lang-btn-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-p-lang-btn" class="vector-dropdown-checkbox mw-interlanguage-selector" aria-label="Go to an article in another language. Available in 60 languages" > <label id="p-lang-btn-label" for="p-lang-btn-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--action-progressive mw-portlet-lang-heading-60" aria-hidden="true" > 60 languages </label> <div class="vector-dropdown-content"> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li class="interlanguage-link interwiki-af mw-list-item"><a href="https://af.wikipedia.org/wiki/Antidepressant" title="Antidepressant – Afrikaans" lang="af" hreflang="af" data-title="Antidepressant" data-language-autonym="Afrikaans" data-language-local-name="Afrikaans" class="interlanguage-link-target">Afrikaans</a></li><li class="interlanguage-link interwiki-ar mw-list-item"><a href="https://ar.wikipedia.org/wiki/%D9%85%D8%B6%D8%A7%D8%AF_%D8%A7%D9%83%D8%AA%D8%A6%D8%A7%D8%A8" title="مضاد اكتئاب – Arabic" lang="ar" hreflang="ar" data-title="مضاد اكتئاب" data-language-autonym="العربية" data-language-local-name="Arabic" class="interlanguage-link-target">العربية</a></li><li class="interlanguage-link interwiki-az mw-list-item"><a href="https://az.wikipedia.org/wiki/Antidepressantlar" title="Antidepressantlar – Azerbaijani" lang="az" hreflang="az" data-title="Antidepressantlar" data-language-autonym="Azərbaycanca" data-language-local-name="Azerbaijani" class="interlanguage-link-target">Azərbaycanca</a></li><li class="interlanguage-link interwiki-be mw-list-item"><a href="https://be.wikipedia.org/wiki/%D0%90%D0%BD%D1%82%D1%8B%D0%B4%D1%8D%D0%BF%D1%80%D1%8D%D1%81%D0%B0%D0%BD%D1%82%D1%8B" title="Антыдэпрэсанты – Belarusian" lang="be" hreflang="be" data-title="Антыдэпрэсанты" data-language-autonym="Беларуская" data-language-local-name="Belarusian" class="interlanguage-link-target">Беларуская</a></li><li class="interlanguage-link interwiki-bg mw-list-item"><a href="https://bg.wikipedia.org/wiki/%D0%90%D0%BD%D1%82%D0%B8%D0%B4%D0%B5%D0%BF%D1%80%D0%B5%D1%81%D0%B0%D0%BD%D1%82" title="Антидепресант – Bulgarian" lang="bg" hreflang="bg" data-title="Антидепресант" data-language-autonym="Български" data-language-local-name="Bulgarian" class="interlanguage-link-target">Български</a></li><li class="interlanguage-link interwiki-bs mw-list-item"><a href="https://bs.wikipedia.org/wiki/Antidepresiv" title="Antidepresiv – Bosnian" lang="bs" hreflang="bs" data-title="Antidepresiv" data-language-autonym="Bosanski" data-language-local-name="Bosnian" class="interlanguage-link-target">Bosanski</a></li><li class="interlanguage-link interwiki-ca mw-list-item"><a href="https://ca.wikipedia.org/wiki/Antidepressiu" title="Antidepressiu – Catalan" lang="ca" hreflang="ca" data-title="Antidepressiu" data-language-autonym="Català" data-language-local-name="Catalan" class="interlanguage-link-target">Català</a></li><li class="interlanguage-link interwiki-cs mw-list-item"><a href="https://cs.wikipedia.org/wiki/Antidepresivum" title="Antidepresivum – Czech" lang="cs" hreflang="cs" data-title="Antidepresivum" data-language-autonym="Čeština" data-language-local-name="Czech" class="interlanguage-link-target">Čeština</a></li><li class="interlanguage-link interwiki-cy mw-list-item"><a href="https://cy.wikipedia.org/wiki/Cyffur_gwrthiselder" title="Cyffur gwrthiselder – Welsh" lang="cy" hreflang="cy" data-title="Cyffur gwrthiselder" data-language-autonym="Cymraeg" data-language-local-name="Welsh" class="interlanguage-link-target">Cymraeg</a></li><li class="interlanguage-link interwiki-da mw-list-item"><a href="https://da.wikipedia.org/wiki/Antidepressivum" title="Antidepressivum – Danish" lang="da" hreflang="da" data-title="Antidepressivum" data-language-autonym="Dansk" data-language-local-name="Danish" class="interlanguage-link-target">Dansk</a></li><li class="interlanguage-link interwiki-de mw-list-item"><a href="https://de.wikipedia.org/wiki/Antidepressivum" title="Antidepressivum – German" lang="de" hreflang="de" data-title="Antidepressivum" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target">Deutsch</a></li><li class="interlanguage-link interwiki-et mw-list-item"><a href="https://et.wikipedia.org/wiki/Antidepressandid" title="Antidepressandid – Estonian" lang="et" hreflang="et" data-title="Antidepressandid" data-language-autonym="Eesti" data-language-local-name="Estonian" class="interlanguage-link-target">Eesti</a></li><li class="interlanguage-link interwiki-el mw-list-item"><a href="https://el.wikipedia.org/wiki/%CE%91%CE%BD%CF%84%CE%B9%CE%BA%CE%B1%CF%84%CE%B1%CE%B8%CE%BB%CE%B9%CF%80%CF%84%CE%B9%CE%BA%CF%8C" title="Αντικαταθλιπτικό – Greek" lang="el" hreflang="el" data-title="Αντικαταθλιπτικό" data-language-autonym="Ελληνικά" data-language-local-name="Greek" class="interlanguage-link-target">Ελληνικά</a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Antidepresivo" title="Antidepresivo – Spanish" lang="es" hreflang="es" data-title="Antidepresivo" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target">Español</a></li><li class="interlanguage-link interwiki-eo mw-list-item"><a href="https://eo.wikipedia.org/wiki/Kontra%C5%ADdeprimilo" title="Kontraŭdeprimilo – Esperanto" lang="eo" hreflang="eo" data-title="Kontraŭdeprimilo" data-language-autonym="Esperanto" data-language-local-name="Esperanto" class="interlanguage-link-target">Esperanto</a></li><li class="interlanguage-link interwiki-eu mw-list-item"><a href="https://eu.wikipedia.org/wiki/Antidepresibo" title="Antidepresibo – Basque" lang="eu" hreflang="eu" data-title="Antidepresibo" data-language-autonym="Euskara" data-language-local-name="Basque" class="interlanguage-link-target">Euskara</a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/%D8%AF%D8%A7%D8%B1%D9%88%D9%87%D8%A7%DB%8C_%D8%B6%D8%AF%D8%A7%D9%81%D8%B3%D8%B1%D8%AF%DA%AF%DB%8C" title="داروهای ضدافسردگی – Persian" lang="fa" hreflang="fa" data-title="داروهای ضدافسردگی" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target">فارسی</a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/Antid%C3%A9presseur" title="Antidépresseur – French" lang="fr" hreflang="fr" data-title="Antidépresseur" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target">Français</a></li><li class="interlanguage-link interwiki-ga mw-list-item"><a href="https://ga.wikipedia.org/wiki/Frithdh%C3%BAlagr%C3%A1n" title="Frithdhúlagrán – Irish" lang="ga" hreflang="ga" data-title="Frithdhúlagrán" data-language-autonym="Gaeilge" data-language-local-name="Irish" class="interlanguage-link-target">Gaeilge</a></li><li class="interlanguage-link interwiki-gl mw-list-item"><a href="https://gl.wikipedia.org/wiki/Antidepresivo" title="Antidepresivo – Galician" lang="gl" hreflang="gl" data-title="Antidepresivo" data-language-autonym="Galego" data-language-local-name="Galician" class="interlanguage-link-target">Galego</a></li><li class="interlanguage-link interwiki-ko mw-list-item"><a href="https://ko.wikipedia.org/wiki/%ED%95%AD%EC%9A%B0%EC%9A%B8%EC%A0%9C" title="항우울제 – Korean" lang="ko" hreflang="ko" data-title="항우울제" data-language-autonym="한국어" data-language-local-name="Korean" class="interlanguage-link-target">한국어</a></li><li class="interlanguage-link interwiki-hy mw-list-item"><a href="https://hy.wikipedia.org/wiki/%D5%80%D5%A1%D5%AF%D5%A1%D5%A4%D5%A5%D5%BA%D6%80%D5%A5%D5%BD%D5%A1%D5%B6%D5%BF%D5%B6%D5%A5%D6%80" title="Հակադեպրեսանտներ – Armenian" lang="hy" hreflang="hy" data-title="Հակադեպրեսանտներ" data-language-autonym="Հայերեն" data-language-local-name="Armenian" class="interlanguage-link-target">Հայերեն</a></li><li class="interlanguage-link interwiki-hr mw-list-item"><a href="https://hr.wikipedia.org/wiki/Antidepresivi" title="Antidepresivi – Croatian" lang="hr" hreflang="hr" data-title="Antidepresivi" data-language-autonym="Hrvatski" data-language-local-name="Croatian" class="interlanguage-link-target">Hrvatski</a></li><li class="interlanguage-link interwiki-id mw-list-item"><a href="https://id.wikipedia.org/wiki/Antidepresan" title="Antidepresan – Indonesian" lang="id" hreflang="id" data-title="Antidepresan" data-language-autonym="Bahasa Indonesia" data-language-local-name="Indonesian" class="interlanguage-link-target">Bahasa Indonesia</a></li><li class="interlanguage-link interwiki-is mw-list-item"><a href="https://is.wikipedia.org/wiki/%C3%9Eunglyndislyf" title="Þunglyndislyf – Icelandic" lang="is" hreflang="is" data-title="Þunglyndislyf" data-language-autonym="Íslenska" data-language-local-name="Icelandic" class="interlanguage-link-target">Íslenska</a></li><li class="interlanguage-link interwiki-it mw-list-item"><a href="https://it.wikipedia.org/wiki/Antidepressivo" title="Antidepressivo – Italian" lang="it" hreflang="it" data-title="Antidepressivo" data-language-autonym="Italiano" data-language-local-name="Italian" class="interlanguage-link-target">Italiano</a></li><li class="interlanguage-link interwiki-he mw-list-item"><a href="https://he.wikipedia.org/wiki/%D7%AA%D7%A8%D7%95%D7%A4%D7%95%D7%AA_%D7%A0%D7%95%D7%92%D7%93%D7%95%D7%AA_%D7%93%D7%99%D7%9B%D7%90%D7%95%D7%9F" title="תרופות נוגדות דיכאון – Hebrew" lang="he" hreflang="he" data-title="תרופות נוגדות דיכאון" data-language-autonym="עברית" data-language-local-name="Hebrew" class="interlanguage-link-target">עברית</a></li><li class="interlanguage-link interwiki-kn mw-list-item"><a href="https://kn.wikipedia.org/wiki/%E0%B2%96%E0%B2%BF%E0%B2%A8%E0%B3%8D%E0%B2%A8%E0%B2%A4%E0%B3%86-%E0%B2%B6%E0%B2%AE%E0%B2%A8%E0%B2%95%E0%B2%BE%E0%B2%B0%E0%B2%BF(%E0%B2%86%E0%B2%82%E0%B2%9F%E0%B2%BF-%E0%B2%A1%E0%B2%BF%E0%B2%AA%E0%B3%8D%E0%B2%B0%E0%B3%86%E0%B2%B8%E0%B3%86%E0%B2%82%E0%B2%9F%E0%B3%8D)" title="ಖಿನ್ನತೆ-ಶಮನಕಾರಿ(ಆಂಟಿ-ಡಿಪ್ರೆಸೆಂಟ್) – Kannada" lang="kn" hreflang="kn" data-title="ಖಿನ್ನತೆ-ಶಮನಕಾರಿ(ಆಂಟಿ-ಡಿಪ್ರೆಸೆಂಟ್)" data-language-autonym="ಕನ್ನಡ" data-language-local-name="Kannada" class="interlanguage-link-target">ಕನ್ನಡ</a></li><li class="interlanguage-link interwiki-ka mw-list-item"><a href="https://ka.wikipedia.org/wiki/%E1%83%90%E1%83%9C%E1%83%A2%E1%83%98%E1%83%93%E1%83%94%E1%83%9E%E1%83%A0%E1%83%94%E1%83%A1%E1%83%90%E1%83%9C%E1%83%A2%E1%83%98" title="ანტიდეპრესანტი – Georgian" lang="ka" hreflang="ka" data-title="ანტიდეპრესანტი" data-language-autonym="ქართული" data-language-local-name="Georgian" class="interlanguage-link-target">ქართული</a></li><li class="interlanguage-link interwiki-sw mw-list-item"><a href="https://sw.wikipedia.org/wiki/Dawa_za_mfadhaiko" title="Dawa za mfadhaiko – Swahili" lang="sw" hreflang="sw" data-title="Dawa za mfadhaiko" data-language-autonym="Kiswahili" data-language-local-name="Swahili" class="interlanguage-link-target">Kiswahili</a></li><li class="interlanguage-link interwiki-ku mw-list-item"><a href="https://ku.wikipedia.org/wiki/Ant%C3%AEdepresan" title="Antîdepresan – Kurdish" lang="ku" hreflang="ku" data-title="Antîdepresan" data-language-autonym="Kurdî" data-language-local-name="Kurdish" class="interlanguage-link-target">Kurdî</a></li><li class="interlanguage-link interwiki-la mw-list-item"><a href="https://la.wikipedia.org/wiki/Antidepressivum" title="Antidepressivum – Latin" lang="la" hreflang="la" data-title="Antidepressivum" data-language-autonym="Latina" data-language-local-name="Latin" class="interlanguage-link-target">Latina</a></li><li class="interlanguage-link interwiki-lv mw-list-item"><a href="https://lv.wikipedia.org/wiki/Antidepresanti" title="Antidepresanti – Latvian" lang="lv" hreflang="lv" data-title="Antidepresanti" data-language-autonym="Latviešu" data-language-local-name="Latvian" class="interlanguage-link-target">Latviešu</a></li><li class="interlanguage-link interwiki-lt mw-list-item"><a href="https://lt.wikipedia.org/wiki/Antidepresantas" title="Antidepresantas – Lithuanian" lang="lt" hreflang="lt" data-title="Antidepresantas" data-language-autonym="Lietuvių" data-language-local-name="Lithuanian" class="interlanguage-link-target">Lietuvių</a></li><li class="interlanguage-link interwiki-hu mw-list-item"><a href="https://hu.wikipedia.org/wiki/Antidepressz%C3%A1ns" title="Antidepresszáns – Hungarian" lang="hu" hreflang="hu" data-title="Antidepresszáns" data-language-autonym="Magyar" data-language-local-name="Hungarian" class="interlanguage-link-target">Magyar</a></li><li class="interlanguage-link interwiki-nl mw-list-item"><a href="https://nl.wikipedia.org/wiki/Antidepressiva" title="Antidepressiva – Dutch" lang="nl" hreflang="nl" data-title="Antidepressiva" data-language-autonym="Nederlands" data-language-local-name="Dutch" class="interlanguage-link-target">Nederlands</a></li><li class="interlanguage-link interwiki-ja mw-list-item"><a href="https://ja.wikipedia.org/wiki/%E6%8A%97%E3%81%86%E3%81%A4%E8%96%AC" title="抗うつ薬 – Japanese" lang="ja" hreflang="ja" data-title="抗うつ薬" data-language-autonym="日本語" data-language-local-name="Japanese" class="interlanguage-link-target">日本語</a></li><li class="interlanguage-link interwiki-no mw-list-item"><a href="https://no.wikipedia.org/wiki/Antidepressivum" title="Antidepressivum – Norwegian Bokmål" lang="nb" hreflang="nb" data-title="Antidepressivum" data-language-autonym="Norsk bokmål" data-language-local-name="Norwegian Bokmål" class="interlanguage-link-target">Norsk bokmål</a></li><li class="interlanguage-link interwiki-nn mw-list-item"><a href="https://nn.wikipedia.org/wiki/Antidepressiva" title="Antidepressiva – Norwegian Nynorsk" lang="nn" hreflang="nn" data-title="Antidepressiva" data-language-autonym="Norsk nynorsk" data-language-local-name="Norwegian Nynorsk" class="interlanguage-link-target">Norsk nynorsk</a></li><li class="interlanguage-link interwiki-uz mw-list-item"><a href="https://uz.wikipedia.org/wiki/Antidepressantlar" title="Antidepressantlar – Uzbek" lang="uz" hreflang="uz" data-title="Antidepressantlar" data-language-autonym="Oʻzbekcha / ўзбекча" data-language-local-name="Uzbek" class="interlanguage-link-target">Oʻzbekcha / ўзбекча</a></li><li class="interlanguage-link interwiki-pap mw-list-item"><a href="https://pap.wikipedia.org/wiki/Antidepresivo" title="Antidepresivo – Papiamento" lang="pap" hreflang="pap" data-title="Antidepresivo" data-language-autonym="Papiamentu" data-language-local-name="Papiamento" class="interlanguage-link-target">Papiamentu</a></li><li class="interlanguage-link interwiki-pl badge-Q17437798 badge-goodarticle mw-list-item" title="good article badge"><a href="https://pl.wikipedia.org/wiki/Leki_przeciwdepresyjne" title="Leki przeciwdepresyjne – Polish" lang="pl" hreflang="pl" data-title="Leki przeciwdepresyjne" data-language-autonym="Polski" data-language-local-name="Polish" class="interlanguage-link-target">Polski</a></li><li class="interlanguage-link interwiki-pt mw-list-item"><a href="https://pt.wikipedia.org/wiki/Antidepressivo" title="Antidepressivo – Portuguese" lang="pt" hreflang="pt" data-title="Antidepressivo" data-language-autonym="Português" data-language-local-name="Portuguese" class="interlanguage-link-target">Português</a></li><li class="interlanguage-link interwiki-ro mw-list-item"><a href="https://ro.wikipedia.org/wiki/Antidepresiv" title="Antidepresiv – Romanian" lang="ro" hreflang="ro" data-title="Antidepresiv" data-language-autonym="Română" data-language-local-name="Romanian" class="interlanguage-link-target">Română</a></li><li class="interlanguage-link interwiki-ru badge-Q17437798 badge-goodarticle mw-list-item" title="good article badge"><a href="https://ru.wikipedia.org/wiki/%D0%90%D0%BD%D1%82%D0%B8%D0%B4%D0%B5%D0%BF%D1%80%D0%B5%D1%81%D1%81%D0%B0%D0%BD%D1%82%D1%8B" title="Антидепрессанты – Russian" lang="ru" hreflang="ru" data-title="Антидепрессанты" data-language-autonym="Русский" data-language-local-name="Russian" class="interlanguage-link-target">Русский</a></li><li class="interlanguage-link interwiki-simple mw-list-item"><a href="https://simple.wikipedia.org/wiki/Antidepressant" title="Antidepressant – Simple English" lang="en-simple" hreflang="en-simple" data-title="Antidepressant" data-language-autonym="Simple English" data-language-local-name="Simple English" class="interlanguage-link-target">Simple English</a></li><li class="interlanguage-link interwiki-sk badge-Q17437798 badge-goodarticle mw-list-item" title="good article badge"><a href="https://sk.wikipedia.org/wiki/Antidepres%C3%ADvum" title="Antidepresívum – Slovak" lang="sk" hreflang="sk" data-title="Antidepresívum" data-language-autonym="Slovenčina" data-language-local-name="Slovak" class="interlanguage-link-target">Slovenčina</a></li><li class="interlanguage-link interwiki-sl mw-list-item"><a href="https://sl.wikipedia.org/wiki/Antidepresiv" title="Antidepresiv – Slovenian" lang="sl" hreflang="sl" data-title="Antidepresiv" data-language-autonym="Slovenščina" data-language-local-name="Slovenian" class="interlanguage-link-target">Slovenščina</a></li><li class="interlanguage-link interwiki-sr mw-list-item"><a href="https://sr.wikipedia.org/wiki/%D0%90%D0%BD%D1%82%D0%B8%D0%B4%D0%B5%D0%BF%D1%80%D0%B5%D1%81%D0%B8%D0%B2" title="Антидепресив – Serbian" lang="sr" hreflang="sr" data-title="Антидепресив" data-language-autonym="Српски / srpski" data-language-local-name="Serbian" class="interlanguage-link-target">Српски / srpski</a></li><li class="interlanguage-link interwiki-sh mw-list-item"><a href="https://sh.wikipedia.org/wiki/Antidepresiv" title="Antidepresiv – Serbo-Croatian" lang="sh" hreflang="sh" data-title="Antidepresiv" data-language-autonym="Srpskohrvatski / српскохрватски" data-language-local-name="Serbo-Croatian" class="interlanguage-link-target">Srpskohrvatski / српскохрватски</a></li><li class="interlanguage-link interwiki-fi mw-list-item"><a href="https://fi.wikipedia.org/wiki/Masennusl%C3%A4%C3%A4kkeet" title="Masennuslääkkeet – Finnish" lang="fi" hreflang="fi" data-title="Masennuslääkkeet" data-language-autonym="Suomi" data-language-local-name="Finnish" class="interlanguage-link-target">Suomi</a></li><li class="interlanguage-link interwiki-sv mw-list-item"><a href="https://sv.wikipedia.org/wiki/Antidepressiva_l%C3%A4kemedel" title="Antidepressiva läkemedel – Swedish" lang="sv" hreflang="sv" data-title="Antidepressiva läkemedel" data-language-autonym="Svenska" data-language-local-name="Swedish" class="interlanguage-link-target">Svenska</a></li><li class="interlanguage-link interwiki-tl mw-list-item"><a href="https://tl.wikipedia.org/wiki/Antidepressant" title="Antidepressant – Tagalog" lang="tl" hreflang="tl" data-title="Antidepressant" data-language-autonym="Tagalog" data-language-local-name="Tagalog" class="interlanguage-link-target">Tagalog</a></li><li class="interlanguage-link interwiki-th mw-list-item"><a href="https://th.wikipedia.org/wiki/%E0%B8%A2%E0%B8%B2%E0%B9%81%E0%B8%81%E0%B9%89%E0%B8%8B%E0%B8%B6%E0%B8%A1%E0%B9%80%E0%B8%A8%E0%B8%A3%E0%B9%89%E0%B8%B2" title="ยาแก้ซึมเศร้า – Thai" lang="th" hreflang="th" data-title="ยาแก้ซึมเศร้า" data-language-autonym="ไทย" data-language-local-name="Thai" class="interlanguage-link-target">ไทย</a></li><li class="interlanguage-link interwiki-tr mw-list-item"><a href="https://tr.wikipedia.org/wiki/Antidepresan" title="Antidepresan – Turkish" lang="tr" hreflang="tr" data-title="Antidepresan" data-language-autonym="Türkçe" data-language-local-name="Turkish" class="interlanguage-link-target">Türkçe</a></li><li class="interlanguage-link interwiki-uk mw-list-item"><a href="https://uk.wikipedia.org/wiki/%D0%90%D0%BD%D1%82%D0%B8%D0%B4%D0%B5%D0%BF%D1%80%D0%B5%D1%81%D0%B0%D0%BD%D1%82" title="Антидепресант – Ukrainian" lang="uk" hreflang="uk" data-title="Антидепресант" data-language-autonym="Українська" data-language-local-name="Ukrainian" class="interlanguage-link-target">Українська</a></li><li class="interlanguage-link interwiki-vi mw-list-item"><a href="https://vi.wikipedia.org/wiki/Thu%E1%BB%91c_ch%E1%BB%91ng_tr%E1%BA%A7m_c%E1%BA%A3m" title="Thuốc chống trầm cảm – Vietnamese" lang="vi" hreflang="vi" data-title="Thuốc chống trầm cảm" data-language-autonym="Tiếng Việt" data-language-local-name="Vietnamese" class="interlanguage-link-target">Tiếng Việt</a></li><li class="interlanguage-link interwiki-wuu mw-list-item"><a href="https://wuu.wikipedia.org/wiki/%E6%8A%97%E6%8A%91%E9%83%81%E8%8D%AF" title="抗抑郁药 – Wu" lang="wuu" hreflang="wuu" data-title="抗抑郁药" data-language-autonym="吴语" data-language-local-name="Wu" class="interlanguage-link-target">吴语</a></li><li class="interlanguage-link interwiki-zh-yue mw-list-item"><a href="https://zh-yue.wikipedia.org/wiki/%E6%8A%97%E6%8A%91%E9%AC%B1%E8%97%A5" title="抗抑鬱藥 – Cantonese" lang="yue" hreflang="yue" data-title="抗抑鬱藥" data-language-autonym="粵語" data-language-local-name="Cantonese" class="interlanguage-link-target">粵語</a></li><li class="interlanguage-link interwiki-zh mw-list-item"><a href="https://zh.wikipedia.org/wiki/%E6%8A%97%E6%8A%91%E9%83%81%E8%8D%AF" title="抗抑郁药 – Chinese" lang="zh" hreflang="zh" data-title="抗抑郁药" data-language-autonym="中文" data-language-local-name="Chinese" class="interlanguage-link-target">中文</a></li> </ul> <div class="after-portlet after-portlet-lang"><a href="https://www.wikidata.org/wiki/Special:EntityPage/Q76560#sitelinks-wikipedia" title="Edit interlanguage links" class="wbc-editpage">Edit links</a></div> </div> </div> </div> </header> <div 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class="noprint">From Wikipedia, the free encyclopedia</div> </div> <div id="contentSub"><div id="mw-content-subtitle"></div></div> <div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Class of medication used to treat depression and other conditions</div> <style data-mw-deduplicate="TemplateStyles:r1257001546">.mw-parser-output .infobox-subbox{padding:0;border:none;margin:-3px;width:auto;min-width:100%;font-size:100%;clear:none;float:none;background-color:transparent}.mw-parser-output .infobox-3cols-child{margin:auto}.mw-parser-output .infobox .navbar{font-size:100%}@media screen{html.skin-theme-clientpref-night .mw-parser-output .infobox-full-data:not(.notheme)>div:not(.notheme)[style]{background:#1f1f23!important;color:#f8f9fa}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .infobox-full-data:not(.notheme) div:not(.notheme){background:#1f1f23!important;color:#f8f9fa}}@media(min-width:640px){body.skin--responsive .mw-parser-output .infobox-table{display:table!important}body.skin--responsive .mw-parser-output .infobox-table>caption{display:table-caption!important}body.skin--responsive .mw-parser-output .infobox-table>tbody{display:table-row-group}body.skin--responsive .mw-parser-output .infobox-table tr{display:table-row!important}body.skin--responsive .mw-parser-output .infobox-table th,body.skin--responsive .mw-parser-output .infobox-table td{padding-left:inherit;padding-right:inherit}}</style><table class="infobox"><tbody><tr><th colspan="2" class="infobox-above" style="background-color: #ddbbee">Antidepressant</th></tr><tr><td colspan="2" class="infobox-subheader"><a href="/wiki/Drug_class" title="Drug class">Drug class</a></td></tr><tr><th colspan="2" class="infobox-header" style="background: #e8e8e8;">Class identifiers</th></tr><tr><th scope="row" class="infobox-label">Use</th><td class="infobox-data"><a href="/wiki/Mood_disorder#Depressive_disorders" title="Mood disorder">Depressive disorders</a>, <a href="/wiki/Anxiety_disorders" class="mw-redirect" title="Anxiety disorders">anxiety disorders</a>, <a href="/wiki/Chronic_pain" title="Chronic pain">chronic pain</a>, and <a href="/wiki/Addiction" title="Addiction">addiction</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Anatomical_Therapeutic_Chemical_Classification_System" title="Anatomical Therapeutic Chemical Classification System">ATC code</a></th><td class="infobox-data"><a href="/wiki/ATC_code_N06A" class="mw-redirect" title="ATC code N06A">N06A</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Mechanism_of_action" title="Mechanism of action">Mechanism of action</a></th><td class="infobox-data">Varies</td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Chemical_classification" class="mw-redirect" title="Chemical classification">Chemical class</a></th><td class="infobox-data">Varies</td></tr><tr><th colspan="2" class="infobox-header" style="background: #e8e8e8;">Clinical data</th></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Drugs.com" title="Drugs.com">Drugs.com</a></th><td class="infobox-data"><a rel="nofollow" class="external text" href="https://www.drugs.com/drug-class/antidepressants.html">Drug Classes</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Consumer_Reports" title="Consumer Reports">Consumer Reports</a></th><td class="infobox-data"><a rel="nofollow" class="external text" href="http://www.consumerreports.org/health/best-buy-drugs/antidepressants.htm">Best Buy Drugs</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/WebMD" title="WebMD">WebMD</a></th><td class="infobox-data"><a rel="nofollow" class="external text" href="http://www.medicinenet.com/antidepressants/article.htm">MedicineNet</a>  <a rel="nofollow" class="external text" href="http://www.rxlist.com/script/main/art.asp?articlekey=100734">RxList</a></td></tr><tr><th colspan="2" class="infobox-header" style="background: #e8e8e8;">External links</th></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Medical_Subject_Headings" title="Medical Subject Headings">MeSH</a></th><td class="infobox-data"><a rel="nofollow" class="external text" href="https://meshb.nlm.nih.gov/record/ui?ui=D000928">D000928</a></td></tr><tr><th colspan="2" class="infobox-header" style="background: #e8e8e8;">Legal status</th></tr><tr><td colspan="2" class="infobox-below" style="background: #e8e8e8; text-align: center"><a href="https://www.wikidata.org/wiki/Q76560" class="extiw" title="d:Q76560">In Wikidata</a></td></tr></tbody></table> <figure class="skin-invert-image" typeof="mw:File/Thumb"><a href="/wiki/File:Venlafaxine_structure.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/7/7d/Venlafaxine_structure.svg/175px-Venlafaxine_structure.svg.png" decoding="async" width="175" height="180" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/7/7d/Venlafaxine_structure.svg/263px-Venlafaxine_structure.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/7/7d/Venlafaxine_structure.svg/350px-Venlafaxine_structure.svg.png 2x" data-file-width="357" data-file-height="367" /></a><figcaption>The skeletal structure of the <a href="/wiki/SNRI" class="mw-redirect" title="SNRI">SNRI</a> <a href="/wiki/Venlafaxine" title="Venlafaxine">venlafaxine</a>, a typical example of an antidepressant.</figcaption></figure> Antidepressants are a class of <a href="/wiki/Medication" title="Medication">medications</a> used to treat <a href="/wiki/Major_depressive_disorder" title="Major depressive disorder">major depressive disorder</a>, <a href="/wiki/Anxiety_disorder" title="Anxiety disorder">anxiety disorders</a>, <a href="/wiki/Chronic_pain" title="Chronic pain">chronic pain</a>, and <a href="/wiki/Addiction" title="Addiction">addiction</a>.<a href="#cite_note-Jennings2018-1">[1]</a> Common <a href="/wiki/Side_effect" title="Side effect">side effects</a> of antidepressants include <a href="/wiki/Xerostomia" title="Xerostomia">dry mouth</a>, <a href="/wiki/Weight_gain" title="Weight gain">weight gain</a>, <a href="/wiki/Dizziness" title="Dizziness">dizziness</a>, <a href="/wiki/Headache" title="Headache">headaches</a>, <a href="/wiki/Akathisia" title="Akathisia">akathisia</a>,<a href="#cite_note-2">[2]</a> <a href="/wiki/Sexual_dysfunction" title="Sexual dysfunction">sexual dysfunction</a>,<a href="#cite_note-3">[3]</a><a href="#cite_note-Bahrick-4">[4]</a><a href="#cite_note-5">[5]</a><a href="#cite_note-6">[6]</a><a href="#cite_note-7">[7]</a> and <a href="/wiki/Emotional_blunting" class="mw-redirect" title="Emotional blunting">emotional blunting</a>.<a href="#cite_note-8">[8]</a><a href="#cite_note-9">[9]</a><a href="#cite_note-10">[10]</a> There is an increased risk of <a href="/wiki/Suicidal_ideation" title="Suicidal ideation">suicidal thinking</a> and <a href="/wiki/Suicide" title="Suicide">behavior</a> when taken by children, adolescents, and young adults.<a href="#cite_note-11">[11]</a> <a href="/wiki/Antidepressant_discontinuation_syndrome" title="Antidepressant discontinuation syndrome">Discontinuation syndrome</a>, which resembles recurrent <a href="/wiki/Depression_(mood)" title="Depression (mood)">depression</a> in the case of the <a href="/wiki/Selective_serotonin_reuptake_inhibitor" title="Selective serotonin reuptake inhibitor">SSRI</a> class, may occur after stopping the intake of any antidepressant, having effects which may be permanent and irreversible.<a href="#cite_note-Wil2015-12">[12]</a><a href="#cite_note-Gab2017-13">[13]</a> Research regarding the effectiveness of antidepressants for depression in adults is controversial and has found both benefits<a href="#cite_note-BarthKriston2018-14">[14]</a> and drawbacks.<a href="#cite_note-BMJ2019-15">[15]</a> Meanwhile, evidence of benefit in children and adolescents is unclear,<a href="#cite_note-CiprianiZhou2016-16">[16]</a><a href="#cite_note-17">[17]</a> even though antidepressant use has considerably increased in children and adolescents in the 2000s.<a href="#cite_note-18">[18]</a> While a 2018 study found that the 21 most commonly prescribed antidepressant medications were slightly more effective than <a href="/wiki/Placebo" title="Placebo">placebos</a> for the short-term (acute) treatments of adults with <a href="/wiki/Major_depressive_disorder" title="Major depressive disorder">major depressive disorder</a>,<a href="#cite_note-NIHR-2018-19">[19]</a><a href="#cite_note-CiprianiFurukawa2018-20">[20]</a> other research has found that the placebo effect may account for most or all of the drugs' observed efficacy.<a href="#cite_note-21">[21]</a><a href="#cite_note-TurnerRosenthal2008-22">[22]</a> Research on the effectiveness of antidepressants is generally done on people who have severe symptoms,<a href="#cite_note-23">[23]</a> a population that exhibits much weaker placebo responses,<a href="#cite_note-24">[24]</a> meaning that the results may not be extrapolated to the general population that has not (or has not yet) been diagnosed with anxiety or depression.<a href="#cite_note-CiprianiFurukawa2018-20">[20]</a> <style data-mw-deduplicate="TemplateStyles:r886046785">.mw-parser-output .toclimit-2 .toclevel-1 ul,.mw-parser-output .toclimit-3 .toclevel-2 ul,.mw-parser-output .toclimit-4 .toclevel-3 ul,.mw-parser-output .toclimit-5 .toclevel-4 ul,.mw-parser-output .toclimit-6 .toclevel-5 ul,.mw-parser-output .toclimit-7 .toclevel-6 ul{display:none}</style><div class="toclimit-3"><meta property="mw:PageProp/toc" /></div> <div class="mw-heading mw-heading2"><h2 id="Medical_uses">Medical uses</h2>[<a href="/w/index.php?title=Antidepressant&action=edit&section=1" title="Edit section: Medical uses">edit</a>]</div> Antidepressants are prescribed to treat <a href="/wiki/Major_depressive_disorder" title="Major depressive disorder">major depressive disorder</a> (MDD), <a href="/wiki/Anxiety_disorder" title="Anxiety disorder">anxiety disorders</a>, <a href="/wiki/Chronic_pain" title="Chronic pain">chronic pain</a>, and some addictions. Antidepressants are often used in combination with one another.<a href="#cite_note-Jennings2018-1">[1]</a> Despite its longstanding prominence in pharmaceutical advertising, the idea that low serotonin levels cause depression is not supported by scientific evidence.<a href="#cite_note-25">[25]</a><a href="#cite_note-26">[26]</a><a href="#cite_note-27">[27]</a> Proponents of the <a href="/wiki/Biology_of_depression" title="Biology of depression">monoamine hypothesis of depression</a> recommend choosing an antidepressant which impacts the most prominent symptoms. Under this practice, for example, a person with MDD who is also anxious or irritable would be treated with <a href="/wiki/Selective_serotonin_reuptake_inhibitor" title="Selective serotonin reuptake inhibitor">selective serotonin reuptake inhibitors</a> (SSRIs) or <a href="/wiki/Norepinephrine_reuptake_inhibitor" title="Norepinephrine reuptake inhibitor">norepinephrine reuptake inhibitors</a>, while a person suffering from loss of energy and enjoyment of life would take a <a href="/wiki/Norepinephrine%E2%80%93dopamine_reuptake_inhibitor" title="Norepinephrine–dopamine reuptake inhibitor">norepinephrine–dopamine reuptake inhibitor</a>.<a href="#cite_note-pmid18494537-28">[28]</a> <div class="mw-heading mw-heading3"><h3 id="Major_depressive_disorder">Major depressive disorder</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=2" title="Edit section: Major depressive disorder">edit</a>]</div> The UK <a href="/wiki/National_Institute_for_Health_and_Care_Excellence" title="National Institute for Health and Care Excellence">National Institute for Health and Care Excellence</a> (NICE)'s 2022 guidelines indicate that antidepressants should not be routinely used for the initial treatment of mild depression, "unless that is the person's preference".<a href="#cite_note-NIHCE-2022-29">[29]</a> The guidelines recommended that antidepressant treatment be considered: <ul><li>For people with a history of moderate or severe depression.</li> <li>For people with mild depression that has been present for an extended period.</li> <li>As a first-line treatment for moderate to severe depression.</li> <li>As a second-line treatment for mild depression that persists after other interventions.</li></ul> The guidelines further note that in most cases, antidepressants should be used in combination with psychosocial interventions and should be continued for at least six months to reduce the risk of relapse and that SSRIs are typically better tolerated than other antidepressants.<a href="#cite_note-NIHCE-2022-29">[29]</a> <a href="/wiki/American_Psychiatric_Association" title="American Psychiatric Association">American Psychiatric Association</a> (APA) treatment guidelines recommend that initial treatment be individually tailored based on factors including the severity of symptoms, co-existing disorders, prior treatment experience, and the person's preference. Options may include antidepressants, <a href="/wiki/Psychotherapy" title="Psychotherapy">psychotherapy</a>, <a href="/wiki/Electroconvulsive_therapy" title="Electroconvulsive therapy">electroconvulsive therapy</a> (ECT), <a href="/wiki/Transcranial_magnetic_stimulation" title="Transcranial magnetic stimulation">transcranial magnetic stimulation</a> (TMS), or <a href="/wiki/Light_therapy" title="Light therapy">light therapy</a>. The APA recommends antidepressant medication as an initial treatment choice in people with mild, moderate, or severe major depression, and that should be given to all people with severe depression unless ECT is planned.<a href="#cite_note-30">[30]</a> Reviews of antidepressants generally find that they benefit adults with depression.<a href="#cite_note-CiprianiFurukawa2018-20">[20]</a><a href="#cite_note-BarthKriston2018-14">[14]</a> On the other hand, some contend that most studies on antidepressant medication are confounded by several biases: the lack of an <a href="/wiki/Active_placebo" title="Active placebo">active placebo</a>, which means that many people in the placebo arm of a <a href="/wiki/Randomized_controlled_trial" title="Randomized controlled trial">double-blind study</a> may deduce that they are not getting any true treatment, thus destroying double-blindness; a short follow up after termination of treatment; non-systematic recording of adverse effects; very strict exclusion criteria in samples of patients; studies being paid for by the industry; selective publication of results. This means that the small beneficial effects that are found may not be statistically significant.<a href="#cite_note-31">[31]</a><a href="#cite_note-32">[32]</a><a href="#cite_note-33">[33]</a><a href="#cite_note-34">[34]</a><a href="#cite_note-BMJ2019-15">[15]</a> Among the 21 most commonly prescribed antidepressants, the most effective and well-tolerated are <a href="/wiki/Escitalopram" title="Escitalopram">escitalopram</a>, <a href="/wiki/Paroxetine" title="Paroxetine">paroxetine</a>, <a href="/wiki/Sertraline" title="Sertraline">sertraline</a>, <a href="/wiki/Agomelatine" title="Agomelatine">agomelatine</a>, and <a href="/wiki/Mirtazapine" title="Mirtazapine">mirtazapine</a>.<a href="#cite_note-NIHR-2018-19">[19]</a><a href="#cite_note-CiprianiFurukawa2018-20">[20]</a> For children and adolescents with moderate to severe depressive disorder, some evidence suggests <a href="/wiki/Fluoxetine" title="Fluoxetine">fluoxetine</a> (either with or without <a href="/wiki/Cognitive_behavioral_therapy" title="Cognitive behavioral therapy">cognitive behavioral therapy</a>) is the best treatment, but more research is needed to be certain.<a href="#cite_note-Evidence-2020-35">[35]</a><a href="#cite_note-Zhou-2020-36">[36]</a><a href="#cite_note-Boaden-2020-37">[37]</a><a href="#cite_note-Hetrick-2021-38">[38]</a> Sertraline, escitalopram, and <a href="/wiki/Duloxetine" title="Duloxetine">duloxetine</a> may also help reduce symptoms.<a href="#cite_note-Hetrick-2021-38">[38]</a> A 2023 <a href="/wiki/Systematic_review" title="Systematic review">systematic review</a> and <a href="/wiki/Meta-analysis" title="Meta-analysis">meta-analysis</a> of <a href="/wiki/Randomized_controlled_trial" title="Randomized controlled trial">randomized controlled trials</a> of antidepressants for major depressive disorder found that the medications provided only small or doubtful benefits in terms of <a href="/wiki/Quality_of_life" title="Quality of life">quality of life</a>.<a href="#cite_note-pmid36905396-39">[39]</a> Likewise, a 2022 systematic review and meta-analysis of randomized controlled trials of antidepressants for major depressive disorder in children and adolescents found small improvements in quality of life.<a href="#cite_note-pmid35508443-40">[40]</a> Quality of life as an outcome measure is often selectively reported in trials of antidepressants.<a href="#cite_note-Paludan-Müller_2021-41">[41]</a> <div class="mw-heading mw-heading3"><h3 id="Anxiety_disorders">Anxiety disorders</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=3" title="Edit section: Anxiety disorders">edit</a>]</div> For children and adolescents, <a href="/wiki/Fluvoxamine" title="Fluvoxamine">fluvoxamine</a> is effective in treating a range of anxiety disorders.<a href="#cite_note-NIHR-2022-42">[42]</a><a href="#cite_note-Boaden-2020-37">[37]</a><a href="#cite_note-Correll-2021-43">[43]</a> Fluoxetine, sertraline, and paroxetine can also help with managing various forms of anxiety in children and adolescents.<a href="#cite_note-NIHR-2022-42">[42]</a><a href="#cite_note-Boaden-2020-37">[37]</a><a href="#cite_note-Correll-2021-43">[43]</a> Meta-analyses of published and unpublished trials have found that antidepressants have a <a href="/wiki/Placebo_group" class="mw-redirect" title="Placebo group">placebo</a>-subtracted <a href="/wiki/Effect_size" title="Effect size">effect size</a> (<a href="/wiki/Standardized_mean_difference" class="mw-redirect" title="Standardized mean difference">standardized mean difference</a> or SMD) in the treatment of anxiety disorders of around 0.3, which equates to a small improvement and is roughly the same magnitude of benefit as their effectiveness in the treatment of depression.<a href="#cite_note-pmid31249537-44">[44]</a> The effect size (SMD) for improvement with placebo in trials of antidepressants for anxiety disorders is approximately 1.0, which is a large improvement in terms of effect size definitions.<a href="#cite_note-pmid31573058-45">[45]</a> In relation to this, most of the benefit of antidepressants for anxiety disorders is attributable to placebo responses rather than to the effects of the antidepressants themselves.<a href="#cite_note-pmid31249537-44">[44]</a><a href="#cite_note-pmid31573058-45">[45]</a> <div class="mw-heading mw-heading4"><h4 id="Generalized_anxiety_disorder">Generalized anxiety disorder</h4>[<a href="/w/index.php?title=Antidepressant&action=edit&section=4" title="Edit section: Generalized anxiety disorder">edit</a>]</div> Antidepressants are recommended by the National Institute for Health and Care Excellence (NICE) for the treatment of <a href="/wiki/Generalized_anxiety_disorder" title="Generalized anxiety disorder">generalized anxiety disorder</a> (GAD) that has failed to respond to conservative measures such as education and self-help activities. GAD is a common disorder in which the central feature is excessively worrying about numerous events. Key symptoms include excessive anxiety about events and issues going on around them and difficulty controlling worrisome thoughts that persists for at least 6 months. Antidepressants provide a modest to moderate reduction in anxiety in GAD.<a href="#cite_note-urlwww.nice.org.uk-46">[46]</a> The efficacy of different antidepressants is similar.<a href="#cite_note-urlwww.nice.org.uk-46">[46]</a> <div class="mw-heading mw-heading4"><h4 id="Social_anxiety_disorder">Social anxiety disorder</h4>[<a href="/w/index.php?title=Antidepressant&action=edit&section=5" title="Edit section: Social anxiety disorder">edit</a>]</div> Some antidepressants are used as a treatment for <a href="/wiki/Social_anxiety_disorder" title="Social anxiety disorder">social anxiety disorder</a>, but their efficacy is not entirely convincing, as only a small proportion of antidepressants showed some effectiveness for this condition. Paroxetine was the first drug to be FDA-approved for this disorder. Its efficacy is considered beneficial, although not everyone responds favorably to the drug. Sertraline and fluvoxamine extended-release were later approved for it as well, while escitalopram is used <a href="/wiki/Off-label_use" title="Off-label use">off-label</a> with acceptable efficiency. However, there is not enough evidence to support <a href="/wiki/Citalopram" title="Citalopram">Citalopram</a> for treating social anxiety disorder, and fluoxetine was no better than a placebo in clinical trials. <a href="/wiki/Selective_serotonin_reuptake_inhibitor" title="Selective serotonin reuptake inhibitor">SSRIs</a> are used as a first-line treatment for social anxiety, but they do not work for everyone. One alternative would be <a href="/wiki/Venlafaxine" title="Venlafaxine">venlafaxine</a>, an <a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitor" title="Serotonin–norepinephrine reuptake inhibitor">SNRI</a>, which has shown benefits for social phobia in five clinical trials against a placebo, while the other SNRIs are not considered particularly useful for this disorder as many of them did not undergo testing for it. As of 2008<a class="external text" href="https://en.wikipedia.org/w/index.php?title=Antidepressant&action=edit">[update]</a>, it is unclear if duloxetine and <a href="/wiki/Desvenlafaxine" title="Desvenlafaxine">desvenlafaxine</a> can provide benefits for people with social anxiety. However, another class of antidepressants called <a href="/wiki/Monoamine_oxidase_inhibitor" title="Monoamine oxidase inhibitor">MAOIs</a> are considered effective for social anxiety, but they come with many unwanted side effects and are rarely used. <a href="/wiki/Phenelzine" title="Phenelzine">Phenelzine</a> was shown to be a good treatment option, but its use is limited by dietary restrictions. <a href="/wiki/Moclobemide" title="Moclobemide">Moclobemide</a> is a <a href="/wiki/Reversible_inhibitor_of_MAO-A" class="mw-redirect" title="Reversible inhibitor of MAO-A">RIMA</a> and showed mixed results, but still received approval in some European countries for social anxiety disorder. <a href="/wiki/Tricyclic_antidepressant" title="Tricyclic antidepressant">TCA antidepressants</a>, such as <a href="/wiki/Clomipramine" title="Clomipramine">clomipramine</a> and <a href="/wiki/Imipramine" title="Imipramine">imipramine</a>, are not considered effective for this anxiety disorder in particular. This leaves out SSRIs such as paroxetine, sertraline, and fluvoxamine CR as acceptable and tolerated treatment options for this disorder.<a href="#cite_note-47">[47]</a><a href="#cite_note-48">[48]</a> <div class="mw-heading mw-heading4"><h4 id="Obsessive–compulsive_disorder">Obsessive–compulsive disorder</h4>[<a href="/w/index.php?title=Antidepressant&action=edit&section=6" title="Edit section: Obsessive–compulsive disorder">edit</a>]</div> SSRIs are a <a href="/wiki/Second-line_medication" class="mw-redirect" title="Second-line medication">second-line</a> treatment for adult <a href="/wiki/Obsessive%E2%80%93compulsive_disorder" title="Obsessive–compulsive disorder">obsessive–compulsive disorder</a> (OCD) with mild functional impairment, and a first-line treatment for those with moderate or severe impairment.<a href="#cite_note-49">[49]</a><a href="#cite_note-50">[50]</a><a href="#cite_note-51">[51]</a><a href="#cite_note-52">[52]</a> In children, SSRIs are considered as a second-line therapy in those with moderate-to-severe impairment, with close monitoring for psychiatric adverse effects.<a href="#cite_note-53">[53]</a> Sertraline and fluoxetine are effective in treating OCD for children and adolescents.<a href="#cite_note-NIHR-2022-42">[42]</a><a href="#cite_note-Boaden-2020-37">[37]</a><a href="#cite_note-Correll-2021-43">[43]</a> <a href="/wiki/Clomipramine" title="Clomipramine">Clomipramine</a>, a TCA drug, is considered effective and useful for OCD. However, it is used as a second-line treatment because it is less well-tolerated than SSRIs. Despite this, it has not shown superiority to fluvoxamine in trials. All SSRIs can be used effectively for OCD. SNRI use may also be attempted, though no SNRIs have been approved for the treatment of OCD. Despite these treatment options, many patients remain symptomatic after initiating the medication, and less than half achieve <a href="/wiki/Remission_(medicine)" title="Remission (medicine)">remission</a>.<a href="#cite_note-54">[54]</a> Placebo responses are a large component of the benefit of antidepressants in the treatment of depression and anxiety.<a href="#cite_note-pmid31249537-44">[44]</a><a href="#cite_note-pmid31573058-45">[45]</a> However, placebo responses with antidepressants are lower in magnitude in the treatment of OCD compared to depression and anxiety.<a href="#cite_note-pmid31573058-45">[45]</a><a href="#cite_note-pmid28477500-55">[55]</a> A 2019 meta-analysis found placebo improvement effect sizes (SMD) of about 1.2 for depression, 1.0 for anxiety disorders, and 0.6 for OCD with antidepressants.<a href="#cite_note-pmid31573058-45">[45]</a> <div class="mw-heading mw-heading4"><h4 id="Post–traumatic_stress_disorder">Post–traumatic stress disorder</h4>[<a href="/w/index.php?title=Antidepressant&action=edit&section=7" title="Edit section: Post–traumatic stress disorder">edit</a>]</div> Antidepressants are one of the treatment options for <a href="/wiki/Post-traumatic_stress_disorder" title="Post-traumatic stress disorder">PTSD</a>. However, their efficacy is not well established. Paroxetine and sertraline have been FDA approved for the treatment of PTSD. Paroxetine has slightly higher response and remission rates than sertraline for this condition. However, neither drug is considered very helpful for a broad patient demographic. Fluoxetine and venlafaxine are used off-label. Fluoxetine has produced unsatisfactory mixed results. Venlafaxine showed response rates of 78%, which is significantly higher than what paroxetine and sertraline achieved. However, it did not address as many symptoms of PTSD as paroxetine and sertraline, in part due to the fact that venlafaxine is an <a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitor" title="Serotonin–norepinephrine reuptake inhibitor">SNRI</a>. This class of drugs inhibits the reuptake of norepinephrine, which may cause anxiety in some patients. Fluvoxamine, escitalopram, and citalopram were not well-tested for this disorder. <a href="/wiki/Monoamine_oxidase_inhibitor" title="Monoamine oxidase inhibitor">MAOIs</a>, while some of them may be helpful, are not used much because of their unwanted side effects. This leaves paroxetine and sertraline as acceptable treatment options for some people, although more effective antidepressants are needed.<a href="#cite_note-56">[56]</a> <div class="mw-heading mw-heading4"><h4 id="Panic_disorder">Panic disorder</h4>[<a href="/w/index.php?title=Antidepressant&action=edit&section=8" title="Edit section: Panic disorder">edit</a>]</div> <a href="/wiki/Panic_disorder" title="Panic disorder">Panic disorder</a> is treated relatively well with medications compared to other disorders. Several classes of antidepressants have shown efficacy for this disorder, with SSRIs and SNRIs used first-line. Paroxetine, sertraline, and fluoxetine are FDA-approved for panic disorder, while fluvoxamine, escitalopram, and citalopram are also considered effective for them. SNRI venlafaxine is also approved for this condition. Unlike <a href="/wiki/Social_anxiety" title="Social anxiety">social anxiety</a> and <a href="/wiki/Post-traumatic_stress_disorder" title="Post-traumatic stress disorder">PTSD</a>, some <a href="/wiki/Tricyclic_antidepressant" title="Tricyclic antidepressant">TCAs antidepressants</a>, like clomipramine and imipramine, have shown efficacy for panic disorder. Moreover, the <a href="/wiki/Monoamine_oxidase_inhibitor" title="Monoamine oxidase inhibitor">MAOI</a> <a href="/wiki/Phenelzine" title="Phenelzine">phenelzine</a> is also considered useful. Panic disorder has many drugs for its treatment. However, the starting dose must be lower than the one used for major depressive disorder because people have reported an increase in anxiety as a result of starting the medication. In conclusion, while panic disorder's treatment options seem acceptable and useful for this condition, many people are still symptomatic after treatment with residual symptoms.<a href="#cite_note-57">[57]</a><a href="#cite_note-58">[58]</a><a href="#cite_note-59">[59]</a> <div class="mw-heading mw-heading3"><h3 id="Eating_disorders">Eating disorders</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=9" title="Edit section: Eating disorders">edit</a>]</div> Antidepressants are recommended as an alternative or additional first step to self-help programs in the treatment of <a href="/wiki/Bulimia_nervosa" title="Bulimia nervosa">bulimia nervosa</a>.<a href="#cite_note-urlwww.nice.org.uk2-60">[60]</a> SSRIs (fluoxetine in particular) are preferred over other antidepressants due to their acceptability, tolerability, and superior reduction of symptoms in short-term trials. Long-term efficacy remains poorly characterized. <a href="/wiki/Bupropion" title="Bupropion">Bupropion</a> is not recommended for the treatment of eating disorders, due to an increased risk of seizure.<a href="#cite_note-61">[61]</a> Similar recommendations apply to <a href="/wiki/Binge_eating_disorder" title="Binge eating disorder">binge eating disorder</a>.<a href="#cite_note-urlwww.nice.org.uk2-60">[60]</a> SSRIs provide short-term reductions in binge eating behavior, but have not been associated with significant weight loss.<a href="#cite_note-urlNational_Guideline_Clearinghouse_|_Practice_guideline_for_the_treatment_of_patients_with_eating_disorders.-62">[62]</a> Clinical trials have generated mostly negative results for the use of SSRIs in the treatment of <a href="/wiki/Anorexia_nervosa" title="Anorexia nervosa">anorexia nervosa</a>.<a href="#cite_note-pmid21414249-63">[63]</a> Treatment guidelines from the National Institute of Health and Care Excellence (NICE)<a href="#cite_note-urlwww.nice.org.uk2-60">[60]</a> recommend against the use of SSRIs in this disorder. Those from the American Psychiatric Association (APA) note that SSRIs confer no advantage regarding weight gain, but may be used for the treatment of co-existing depressive, anxiety, or obsessive–compulsive disorders.<a href="#cite_note-urlNational_Guideline_Clearinghouse_|_Practice_guideline_for_the_treatment_of_patients_with_eating_disorders.-62">[62]</a> <div class="mw-heading mw-heading3"><h3 id="Pain">Pain</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=10" title="Edit section: Pain">edit</a>]</div> <div class="mw-heading mw-heading4"><h4 id="Fibromyalgia">Fibromyalgia</h4>[<a href="/w/index.php?title=Antidepressant&action=edit&section=11" title="Edit section: Fibromyalgia">edit</a>]</div> A 2012 <a href="/wiki/Meta-analysis" title="Meta-analysis">meta-analysis</a> concluded that antidepressant treatment favorably affects pain, health-related quality of life, depression, and sleep in <a href="/wiki/Fibromyalgia" title="Fibromyalgia">fibromyalgia</a> syndrome. <a href="/wiki/Tricyclic_antidepressant" title="Tricyclic antidepressant">Tricyclics</a> appear to be the most effective class, with moderate effects on pain and sleep, and small effects on fatigue and health-related quality of life. The fraction of people experiencing a 30% pain reduction on tricyclics was 48%, versus 28% on placebo. For SSRIs and SNRIs, the fractions of people experiencing a 30% pain reduction were 36% (20% in the placebo comparator arms) and 42% (32% in the corresponding placebo comparator arms) respectively. Discontinuation of treatment due to side effects was common.<a href="#cite_note-64">[64]</a> Antidepressants including <a href="/wiki/Amitriptyline" title="Amitriptyline">amitriptyline</a>, fluoxetine, duloxetine, <a href="/wiki/Milnacipran" title="Milnacipran">milnacipran</a>, <a href="/wiki/Moclobemide" title="Moclobemide">moclobemide</a>, and <a href="/wiki/Pirlindole" title="Pirlindole">pirlindole</a> are recommended by the European League Against Rheumatism (EULAR) for the treatment of fibromyalgia based on "limited evidence".<a href="#cite_note-pmid17644548-65">[65]</a> <div class="mw-heading mw-heading4"><h4 id="Neuropathic_pain">Neuropathic pain</h4>[<a href="/w/index.php?title=Antidepressant&action=edit&section=12" title="Edit section: Neuropathic pain">edit</a>]</div> A 2014 meta-analysis from the <a href="/wiki/Cochrane_Collaboration" class="mw-redirect" title="Cochrane Collaboration">Cochrane Collaboration</a> found the antidepressant duloxetine to be effective for the treatment of pain resulting from <a href="/wiki/Diabetic_neuropathy" title="Diabetic neuropathy">diabetic neuropathy</a>.<a href="#cite_note-66">[66]</a> The same group reviewed data for amitriptyline in the treatment of <a href="/wiki/Neuropathic_pain" title="Neuropathic pain">neuropathic pain</a> and found limited useful randomized clinical trial data. They concluded that the long history of successful use in the community for the treatment of fibromyalgia and neuropathic pain justified its continued use.<a href="#cite_note-Moore2015-67">[67]</a> The group was concerned about the potential overestimation of the amount of pain relief provided by amitriptyline, and highlighted that only a small number of people will experience significant pain relief by taking this medication.<a href="#cite_note-Moore2015-67">[67]</a> <div class="mw-heading mw-heading3"><h3 id="Other_uses">Other uses</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=13" title="Edit section: Other uses">edit</a>]</div> Antidepressants may be modestly helpful for treating people who have both depression and <a href="/wiki/Alcohol_dependence" title="Alcohol dependence">alcohol dependence</a>, however, the evidence supporting this association is of low quality.<a href="#cite_note-68">[68]</a> Bupropion is used to help people <a href="/wiki/Smoking_cessation" title="Smoking cessation">stop smoking</a>. Antidepressants are also used to control some symptoms of <a href="/wiki/Narcolepsy" title="Narcolepsy">narcolepsy</a>.<a href="#cite_note-69">[69]</a> Antidepressants may be used to relieve pain in people with active <a href="/wiki/Rheumatoid_arthritis" title="Rheumatoid arthritis">rheumatoid arthritis</a>. However, further research is required.<a href="#cite_note-70">[70]</a> Antidepressants have been shown to be superior to placebo in treating depression in individuals with physical illness, although reporting bias may have exaggerated this finding.<a href="#cite_note-71">[71]</a> Antidepressants have been shown to improve some parts of cognitive functioning for depressed users, such as memory, attention, and processing speed.<a href="#cite_note-72">[72]</a> Certain antidepressants acting as serotonin 5-HT2A receptor antagonists, such as <a href="/wiki/Trazodone" title="Trazodone">trazodone</a> and <a href="/wiki/Mirtazapine" title="Mirtazapine">mirtazapine</a>, have been used as <a href="/wiki/Trip_killer" title="Trip killer">hallucinogen antidotes or "trip killers"</a> to block the effects of <a href="/wiki/Serotonergic_psychedelic" class="mw-redirect" title="Serotonergic psychedelic">serotonergic psychedelics</a> like <a href="/wiki/Psilocybin" title="Psilocybin">psilocybin</a> and <a href="/wiki/Lysergic_acid_diethylamide" class="mw-redirect" title="Lysergic acid diethylamide">lysergic acid diethylamide</a> (LSD).<a href="#cite_note-HalmanKongSarris2024-73">[73]</a><a href="#cite_note-YatesMelon2024-74">[74]</a><a href="#cite_note-Suran2024-75">[75]</a> <div class="mw-heading mw-heading3"><h3 id="Limitations_and_strategies">Limitations and strategies</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=14" title="Edit section: Limitations and strategies">edit</a>]</div> Among individuals treated with a given antidepressant, between 30% and 50% do not show a response.<a href="#cite_note-76">[76]</a><a href="#cite_note-SSRIswitch-77">[77]</a> Approximately one-third of people achieve a full <a href="/wiki/Remission_(medicine)" title="Remission (medicine)">remission</a>, one-third experience a response, and one-third are non-responders. Partial remission is characterized by the presence of poorly defined residual symptoms. These symptoms typically include depressed mood, anxiety, sleep disturbance, fatigue, and diminished interest or pleasure. It is currently unclear which factors predict partial remission. However, it is clear that residual symptoms are powerful predictors of relapse, with relapse rates three to six times higher in people with residual symptoms than in those, who experience full remission.<a href="#cite_note-78">[78]</a> In addition, antidepressant drugs tend to lose efficacy throughout long-term <a href="/wiki/Maintenance_therapy" title="Maintenance therapy">maintenance therapy</a>.<a href="#cite_note-79">[79]</a> According to data from the <a href="/wiki/Centers_for_Disease_Control_and_Prevention" title="Centers for Disease Control and Prevention">Centers for Disease Control and Prevention</a>, less than one-third of Americans taking one antidepressant medication have seen a mental health professional in the previous year.<a href="#cite_note-80">[80]</a> Several strategies are used in clinical practice to try to overcome these limits and variations.<a href="#cite_note-81">[81]</a> They include switching medication, augmentation, and combination. There is controversy amongst researchers regarding the efficacy and risk-benefit ratio of antidepressants.<a href="#cite_note-Wilson2018-82">[82]</a><a href="#cite_note-Warren2020-83">[83]</a> Although antidepressants consistently out-perform a placebo in meta-analyses, the difference is modest and it is not clear that their statistical superiority results in clinical efficacy.<a href="#cite_note-CiprianiFurukawa2018-20">[20]</a><a href="#cite_note-pmid35918097-84">[84]</a><a href="#cite_note-pmid30386270-85">[85]</a><a href="#cite_note-McCormack2018-86">[86]</a> The aggregate effect of antidepressants typically results in changes below the threshold of clinical significance on depression rating scales.<a href="#cite_note-pmid31554608-87">[87]</a><a href="#cite_note-pmid25979317-88">[88]</a> Proponents of antidepressants counter that the most common scale, the <a href="/wiki/HDRS" class="mw-redirect" title="HDRS">HDRS</a>, is not suitable for assessing drug action, that the threshold for clinical significance is arbitrary, and that antidepressants consistently result in significantly raised scores on the mood item of the scale.<a href="#cite_note-Pariante2022-89">[89]</a> Assessments of antidepressants using alternative, more sensitive scales, such as the <a href="/wiki/Montgomery%E2%80%93%C3%85sberg_Depression_Rating_Scale" title="Montgomery–Åsberg Depression Rating Scale">MADRS</a>, do not result in marked difference from the HDRS and likewise only find a marginal clinical benefit.<a href="#cite_note-pmid32101579-90">[90]</a> Another hypothesis proposed to explain the poor performance of antidepressants in clinical trials is a high treatment response heterogeneity. Some patients, that differ strongly in their response to antidepressants, could influence the average response, while the heterogeneity could itself be obscured by the averaging. Studies have not supported this hypothesis, but it is very difficult to measure treatment effect heterogeneity.<a href="#cite_note-Luedtke2021-91">[91]</a> Poor and complex clinical trial design might also account for the small effects seen for antidepressants.<a href="#cite_note-Khan2015-92">[92]</a><a href="#cite_note-Nutt2008-93">[93]</a> The randomized controlled trials used to approve drugs are short, and may not capture the full effect of antidepressants.<a href="#cite_note-Nutt2008-93">[93]</a> Additionally, the placebo effect might be inflated in these trials by frequent clinical consultation, lowering the comparative performance of antidepressants.<a href="#cite_note-Nutt2008-93">[93]</a> Critics agree that current clinical trials are poorly-designed, which limits the knowledge on antidepressants.<a href="#cite_note-Boesen2021-94">[94]</a> More naturalistic studies, such as <a href="/wiki/STAR*D" title="STAR*D">STAR*D</a>, have produced results, which suggest that antidepressants may be less effective in clinical practice than in randomized controlled trials.<a href="#cite_note-Read2022-95">[95]</a><a href="#cite_note-96">[96]</a> Critics of antidepressants maintain that the superiority of antidepressants over placebo is the result of systemic flaws in clinical trials and the research literature.<a href="#cite_note-Read2022-95">[95]</a><a href="#cite_note-pmid31554608-87">[87]</a> Trials conducted with industry involvement tend to produce more favorable results, and accordingly many of the trials included in meta-analyses are at high risk of bias.<a href="#cite_note-pmid31248914-97">[97]</a><a href="#cite_note-pmid31554608-87">[87]</a> Additionally, meta-analyses co-authored by industry employees find more favorable results for antidepressants.<a href="#cite_note-pmid31554608-87">[87]</a> The results of antidepressant trials are significantly more likely to be published if they are favorable, and unfavorable results are very often left unpublished or misreported, a phenomenon called <a href="/wiki/Publication_bias" title="Publication bias">publication bias</a> or selective publication.<a href="#cite_note-Turner2008-98">[98]</a> Although this issue has diminished with time, it remains an obstacle to accurately assessing the efficacy of antidepressants.<a href="#cite_note-Turner2022-99">[99]</a> Misreporting of clinical trial outcomes and of serious adverse events, such as suicide, is common.<a href="#cite_note-Hughes2014-100">[100]</a><a href="#cite_note-pmid31248914-97">[97]</a><a href="#cite_note-Hengartner2022-101">[101]</a> <a href="/wiki/Ghostwriting" class="mw-redirect" title="Ghostwriting">Ghostwriting</a> of antidepressant trials is widespread, a practice in which prominent researchers, or so-called key opinion leaders, attach their names to studies actually written by pharmaceutical company employees or consultants.<a href="#cite_note-Hengartner2022-101">[101]</a> A particular concern is that the psychoactive effects of antidepressants may lead to the unblinding of participants or researchers, enhancing the placebo effect and biasing results.<a href="#cite_note-pmid31249537-44">[44]</a><a href="#cite_note-Kirsch2014-102">[102]</a><a href="#cite_note-pmid31248914-97">[97]</a> Some have therefore maintained that antidepressants may only be active placebos.<a href="#cite_note-Read2022-95">[95]</a><a href="#cite_note-pmid31554608-87">[87]</a> When these and other flaws in the research literature are not taken into account, meta-analyses may find inflated results on the basis of poor evidence.<a href="#cite_note-pmid31248914-97">[97]</a> Critics contend that antidepressants have not been proven sufficiently effective by RCTs or in clinical practice and that the widespread use of antidepressants is not evidence-based.<a href="#cite_note-Read2022-95">[95]</a><a href="#cite_note-pmid31554608-87">[87]</a> They also note that adverse effects, including withdrawal difficulties, are likely underreported, skewing clinicians' ability to make risk-benefit judgements.<a href="#cite_note-Warren2020-83">[83]</a><a href="#cite_note-Sharma2016-103">[103]</a><a href="#cite_note-Bielefeldt2016-104">[104]</a><a href="#cite_note-Read2022-95">[95]</a> Accordingly, they believe antidepressants are overused, particularly for non-severe depression and conditions in which they are not indicated.<a href="#cite_note-Warren2020-83">[83]</a><a href="#cite_note-Fava2014-105">[105]</a> Critics charge that the widespread use and public acceptance of antidepressants is the result of pharmaceutical advertising, research manipulation, and misinformation.<a href="#cite_note-pmid16268734-106">[106]</a><a href="#cite_note-LacasseLeo2015-107">[107]</a><a href="#cite_note-Lacasse2005-108">[108]</a><a href="#cite_note-AngHorowitzMoncrieff2022-109">[109]</a> Current mainstream psychiatric opinion recognizes the limitations of antidepressants but recommends their use in adults with more severe depression as a first-line treatment.<a href="#cite_note-nrdp2016-110">[110]</a><a href="#cite_note-NICE2022-111">[111]</a> <div class="mw-heading mw-heading3"><h3 id="Switching_antidepressants">Switching antidepressants</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=15" title="Edit section: Switching antidepressants">edit</a>]</div> <style data-mw-deduplicate="TemplateStyles:r1236090951">.mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em}@media print{body.ns-0 .mw-parser-output .hatnote{display:none!important}}</style><div role="note" class="hatnote navigation-not-searchable">See also: <a href="/wiki/Treatment-resistant_depression#Switching_antidepressants" title="Treatment-resistant depression">Treatment-resistant depression § Switching antidepressants</a></div> The <a href="/wiki/American_Psychiatric_Association" title="American Psychiatric Association">American Psychiatric Association</a> 2000 Practice Guideline advises that where no response is achieved within the following six to eight weeks of treatment with an antidepressant, switch to an antidepressant in the same class, and then to a different class. A 2006 meta-analysis review found wide variation in the findings of prior studies: for people who had failed to respond to an SSRI antidepressant, between 12% and 86% showed a response to a new drug. However, the more antidepressants an individual had previously tried, the less likely they were to benefit from a new antidepressant trial.<a href="#cite_note-SSRIswitch-77">[77]</a> However, a later meta-analysis found no difference between switching to a new drug and staying on the old medication: although 34% of <a href="/wiki/Treatment-resistant_depression" title="Treatment-resistant depression">treatment-resistant</a> people responded when switched to the new drug, 40% responded without being switched.<a href="#cite_note-112">[112]</a> <div class="mw-heading mw-heading3"><h3 id="Augmentation_and_combination">Augmentation and combination</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=16" title="Edit section: Augmentation and combination">edit</a>]</div> For a partial response, the American Psychiatric Association (APA) guidelines suggest <a href="/wiki/Augmentation_(pharmacology)" title="Augmentation (pharmacology)">augmentation</a> or adding a drug from a different class. These include <a href="/wiki/Lithium_(medication)" title="Lithium (medication)">lithium</a> and <a href="/wiki/Thyroid" title="Thyroid">thyroid</a> augmentation, <a href="/wiki/Dopamine_agonist" title="Dopamine agonist">dopamine agonists</a>, <a href="/wiki/Sex_steroid" class="mw-redirect" title="Sex steroid">sex steroids</a>, <a href="/wiki/Norepinephrine_reuptake_inhibitor" title="Norepinephrine reuptake inhibitor">NRIs</a>, <a href="/wiki/Glucocorticoid" title="Glucocorticoid">glucocorticoid</a>-specific agents, or the newer <a href="/wiki/Anticonvulsant" title="Anticonvulsant">anticonvulsants</a>.<a href="#cite_note-augment-113">[113]</a> A combination strategy involves adding another antidepressant, usually from a different class to affect other mechanisms. Although this may be used in clinical practice, there is little evidence for the relative efficacy or adverse effects of this strategy.<a href="#cite_note-114">[114]</a> Other tests conducted include the use of <a href="/wiki/Psychostimulant" class="mw-redirect" title="Psychostimulant">psychostimulants</a> as an augmentation therapy. Several studies have shown the efficacy of combining <a href="/wiki/Modafinil" title="Modafinil">modafinil</a> for treatment-resistant people. It has been used to help combat SSRI-associated fatigue.<a href="#cite_note-115">[115]</a> <div class="mw-heading mw-heading3"><h3 id="Long-term_use_and_stopping">Long-term use and stopping</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=17" title="Edit section: Long-term use and stopping">edit</a>]</div> The effects of antidepressants typically do not continue once the course of medication ends. This results in a high rate of <a href="/wiki/Relapse" title="Relapse">relapse</a>. In 2003, a <a href="/wiki/Meta-analysis" title="Meta-analysis">meta-analysis</a> found that 18% of people who had responded to an antidepressant relapsed while still taking it, compared to 41% whose antidepressant was switched for a <a href="/wiki/Placebo" title="Placebo">placebo</a>.<a href="#cite_note-116">[116]</a> A gradual loss of therapeutic benefit occurs in a minority of people during the course of treatment.<a href="#cite_note-117">[117]</a><a href="#cite_note-fava-118">[118]</a> A strategy involving the use of <a href="/wiki/Pharmacotherapy" title="Pharmacotherapy">pharmacotherapy</a> in the treatment of the acute episode, followed by psychotherapy in its residual phase, has been suggested by some studies.<a href="#cite_note-119">[119]</a><a href="#cite_note-120">[120]</a> For patients who wish to stop their antidepressants, engaging in brief psychological interventions such as Preventive Cognitive Therapy<a href="#cite_note-121">[121]</a> or <a href="/wiki/Mindfulness-based_cognitive_therapy" title="Mindfulness-based cognitive therapy">mindfulness-based cognitive therapy</a> while tapering down has been found to diminish the risk for <a href="/wiki/Relapse_prevention" title="Relapse prevention">relapse</a>.<a href="#cite_note-122">[122]</a> <div class="mw-heading mw-heading2"><h2 id="Adverse_effects">Adverse effects</h2>[<a href="/w/index.php?title=Antidepressant&action=edit&section=18" title="Edit section: Adverse effects">edit</a>]</div> Antidepressants can cause various <a href="/wiki/Adverse_effects" class="mw-redirect" title="Adverse effects">adverse effects</a>, depending on the individual and the drug in question.<a href="#cite_note-123">[123]</a> Almost any medication involved with serotonin regulation has the potential to cause <a href="/wiki/Serotonin_syndrome" title="Serotonin syndrome">serotonin toxicity</a> (also known as serotonin syndrome) – an excess of serotonin that can induce mania, restlessness, agitation, <a href="/wiki/Emotional_lability" title="Emotional lability">emotional lability</a>, insomnia, and confusion as its primary symptoms.<a href="#cite_note-pmid12771076-124">[124]</a><a href="#cite_note-pmid15784664-125">[125]</a> Although the condition is serious, it is not particularly common, generally only appearing at high doses or while on other medications. Assuming proper medical intervention has been taken (within about 24 hours) it is rarely fatal.<a href="#cite_note-pmid10941349-126">[126]</a><a href="#cite_note-pmid10818648-127">[127]</a> Antidepressants appear to increase the risk of <a href="/wiki/Diabetes" title="Diabetes">diabetes</a> by about 1.3-fold.<a href="#cite_note-Salvi_2017-128">[128]</a> <a href="/wiki/MAOIs" class="mw-redirect" title="MAOIs">MAOIs</a> tend to have pronounced (sometimes fatal) interactions with a wide variety of medications and <a href="/wiki/Over-the-counter_drug" title="Over-the-counter drug">over-the-counter drugs</a>. If taken with foods that contain very high levels of <a href="/wiki/Tyramine" title="Tyramine">tyramine</a> (e.g., mature cheese, cured meats, or yeast extracts), they may cause a potentially lethal <a href="/wiki/Hypertensive_crisis" title="Hypertensive crisis">hypertensive crisis</a>. At lower doses, the person may only experience a headache due to an increase in blood pressure.<a href="#cite_note-pmid19742203-129">[129]</a> In response to these adverse effects, a different type of MAOI, the class of <a href="/wiki/Reversible_inhibitor_of_monoamine_oxidase_A" class="mw-redirect" title="Reversible inhibitor of monoamine oxidase A">reversible inhibitor of monoamine oxidase A</a> (RIMA), has been developed. The primary advantage of RIMAs is that they do not require the person to follow a special diet while being purportedly effective as SSRIs and tricyclics in treating depressive disorders.<a href="#cite_note-pmid7717091-130">[130]</a> Tricyclics and SSRI can cause the so-called <a href="/wiki/Drug-induced_QT_prolongation" title="Drug-induced QT prolongation">drug-induced QT prolongation</a>, especially in older adults;<a href="#cite_note-131">[131]</a> this condition can degenerate into a specific type of <a href="/wiki/Heart_arrhythmia" class="mw-redirect" title="Heart arrhythmia">abnormal heart rhythm</a> called <a href="/wiki/Torsades_de_pointes" title="Torsades de pointes">Torsades de points</a>, which can potentially lead to <a href="/wiki/Cardiac_arrest" title="Cardiac arrest">sudden cardiac arrest</a>.<a href="#cite_note-132">[132]</a> Some antidepressants are also believed to increase thoughts of <a href="/wiki/Suicidal_ideation" title="Suicidal ideation">suicidal ideation</a>. Antidepressants have been associated with an increased risk of <a href="/wiki/Dementia" title="Dementia">dementia</a> in older adults.<a href="#cite_note-pmid37834986-133">[133]</a> Researchers have developed a tool that allows people to rate their concern about common side effects of antidepressants. The tool ranks potential treatment options in a visual display that highlights the drugs with side effects of least concern to an individual.<a href="#cite_note-134">[134]</a><a href="#cite_note-135">[135]</a> <div class="mw-heading mw-heading3"><h3 id="Pregnancy">Pregnancy</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=19" title="Edit section: Pregnancy">edit</a>]</div> SSRI use in pregnancy has been associated with a variety of risks with varying degrees of proof of causation. As depression is independently associated with negative pregnancy outcomes, determining the extent to which observed associations between antidepressant use and specific adverse outcomes reflect a causative relationship has been difficult in some cases.<a href="#cite_note-136">[136]</a> In other cases, the attribution of adverse outcomes to antidepressant exposure seems fairly clear. SSRI use in pregnancy is associated with an increased risk of spontaneous abortion of about 1.7-fold,<a href="#cite_note-137">[137]</a><a href="#cite_note-pmid23351929-138">[138]</a> and is associated with preterm birth and low birth weight.<a href="#cite_note-139">[139]</a> A systematic review of the risk of major birth defects in antidepressant-exposed pregnancies found a small increase (3% to 24%) in the risk of major malformations and a risk of cardiovascular birth defects that did not differ from non-exposed pregnancies.<a href="#cite_note-140">[140]</a> A study of fluoxetine-exposed pregnancies found a 12% increase in the risk of major malformations that did not reach statistical significance.<a href="#cite_note-141">[141]</a> Other studies have found an increased risk of cardiovascular birth defects among depressed mothers not undergoing SSRI treatment, suggesting the possibility of ascertainment bias, e.g. that worried mothers may pursue more aggressive testing of their infants.<a href="#cite_note-142">[142]</a> Another study found no increase in cardiovascular birth defects and a 27% increased risk of major malformations in SSRI exposed pregnancies.<a href="#cite_note-pmid23351929-138">[138]</a> The FDA advises for the risk of birth defects with the use of paroxetine<a href="#cite_note-143">[143]</a> and the MAOI should be avoided. A 2013 systematic review and meta-analysis found that antidepressant use during pregnancy was statistically significantly associated with some pregnancy outcomes, such as gestational age and preterm birth, but not with other outcomes. The same review cautioned that because differences between the exposed and unexposed groups were small, it was doubtful whether they were clinically significant.<a href="#cite_note-144">[144]</a> A <a href="/wiki/Neonate" class="mw-redirect" title="Neonate">neonate</a> (infant less than 28 days old) may experience a <a href="/wiki/Withdrawal_syndrome" class="mw-redirect" title="Withdrawal syndrome">withdrawal syndrome</a> from abrupt discontinuation of the antidepressant at birth. Antidepressants can be present in varying amounts in breast milk, but their effects on infants are currently unknown.<a href="#cite_note-145">[145]</a> Moreover, SSRIs inhibit nitric oxide synthesis, which plays an important role in setting the vascular tone. Several studies have pointed to an increased risk of prematurity associated with SSRI use, and this association may be due to an increased risk of <a href="/wiki/Pre-eclampsia" title="Pre-eclampsia">pre-eclampsia</a> during pregnancy.<a href="#cite_note-146">[146]</a> <div class="mw-heading mw-heading3"><h3 id="Antidepressant-induced_mania">Antidepressant-induced mania</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=20" title="Edit section: Antidepressant-induced mania">edit</a>]</div> Another possible problem with antidepressants is the chance of antidepressant-induced <a href="/wiki/Mania" title="Mania">mania</a> or <a href="/wiki/Hypomania" title="Hypomania">hypomania</a> in people with or without a diagnosis of <a href="/wiki/Bipolar_disorder" title="Bipolar disorder">bipolar disorder</a>. Many cases of bipolar depression are very similar to those of unipolar depression. Therefore, the person can be misdiagnosed with unipolar depression and be given antidepressants. Studies have shown that antidepressant-induced mania can occur in 20–40% of people with bipolar disorder.<a href="#cite_note-147">[147]</a> For bipolar depression, antidepressants (most frequently SSRIs) can exacerbate or trigger symptoms of hypomania and mania.<a href="#cite_note-pmid9387089-148">[148]</a> <a href="/wiki/Bupropion" title="Bupropion">Bupropion</a> has been associated with a lower risk of mood switch than other antidepressants.<a href="#cite_note-pmid37119556-149">[149]</a> <div class="mw-heading mw-heading3"><h3 id="Suicide">Suicide</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=21" title="Edit section: Suicide">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Antidepressants_and_suicide_risk" title="Antidepressants and suicide risk">Antidepressants and suicide risk</a></div> Studies have shown that the use of antidepressants is correlated with an increased risk of suicidal behavior and thinking (suicidality) in those aged under 25 years old.<a href="#cite_note-StoneETAL-150">[150]</a> This problem has been serious enough to warrant government intervention by the US Food and Drug Administration (FDA) to warn of the increased risk of suicidality during antidepressant treatment.<a href="#cite_note-pmid17485726-151">[151]</a> According to the FDA, the heightened risk of suicidality occurs within the first one to two months of treatment.<a href="#cite_note-152">[152]</a><a href="#cite_note-153">[153]</a> The National Institute for Health and Care Excellence (NICE) places the excess risk in the "early stages of treatment".<a href="#cite_note-154">[154]</a> A <a href="/wiki/Meta-analysis" title="Meta-analysis">meta-analysis</a> suggests that the relationship between antidepressant use and suicidal behavior or thoughts is age-dependent.<a href="#cite_note-StoneETAL-150">[150]</a> Compared with placebo, the use of antidepressants is associated with an increase in suicidal behavior or thoughts among those 25 years old or younger (<a href="/wiki/Odds_ratio" title="Odds ratio">OR</a>=1.62). A review of RCTs and epidemiological studies by Healy and Whitaker found an increase in suicidal acts by a factor of 2.4.<a href="#cite_note-155">[155]</a> There is no effect or possibly a mild protective effect among those aged 25 to 64 (OR=0.79). Antidepressant treatment has a protective effect against suicidality among those aged 65 and over (OR=0.37).<a href="#cite_note-StoneETAL-150">[150]</a><a href="#cite_note-dhintrev-156">[156]</a> <div class="mw-heading mw-heading3"><h3 id="Sexual_dysfunction">Sexual dysfunction</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=22" title="Edit section: Sexual dysfunction">edit</a>]</div> Sexual side effects are also common with SSRIs, such as loss of <a href="/wiki/Sexual_drive" class="mw-redirect" title="Sexual drive">sexual drive</a>, <a href="/wiki/Anorgasmia" title="Anorgasmia">failure to reach orgasm</a>, and <a href="/wiki/Erectile_dysfunction" title="Erectile dysfunction">erectile dysfunction</a>.<a href="#cite_note-157">[157]</a> Although usually reversible, these sexual side-effects can, in rare cases, continue after the drug has been completely withdrawn.<a href="#cite_note-pmid18173768-158">[158]</a><a href="#cite_note-159">[159]</a> In a study of 1,022 outpatients, overall sexual dysfunction with all antidepressants averaged 59.1%<a href="#cite_note-pmid11229449-160">[160]</a> with SSRI values between 57% and 73%, mirtazapine 24%, nefazodone 8%, amineptine 7%, and <a href="/wiki/Moclobemide" title="Moclobemide">moclobemide</a> 4%. Moclobemide, a selective reversible MAO-A inhibitor, does not cause sexual dysfunction<a href="#cite_note-pmid19440080-161">[161]</a> and can lead to an improvement in all aspects of sexual function.<a href="#cite_note-pmid9696909-162">[162]</a> Biochemical mechanisms suggested as causative include increased serotonin, particularly affecting <a href="/wiki/5-HT2_receptor" title="5-HT2 receptor">5-HT2</a> and <a href="/wiki/5HT3_receptor" class="mw-redirect" title="5HT3 receptor">5-HT3 receptors</a>; decreased <a href="/wiki/Dopamine" title="Dopamine">dopamine</a>; decreased <a href="/wiki/Norepinephrine" title="Norepinephrine">norepinephrine</a>; blockade of <a href="/wiki/Cholinergic_receptor" class="mw-redirect" title="Cholinergic receptor">cholinergic</a> and <a href="/wiki/Alpha-1_adrenergic_receptor" title="Alpha-1 adrenergic receptor">α1adrenergic receptors</a>; inhibition of <a href="/wiki/Nitric_oxide_synthase" title="Nitric oxide synthase">nitric oxide synthetase</a>; and elevation of <a href="/wiki/Prolactin" title="Prolactin">prolactin</a> levels.<a href="#cite_note-163">[163]</a> <a href="/wiki/Mirtazapine" title="Mirtazapine">Mirtazapine</a> is reported to have fewer sexual side effects, most likely because it antagonizes 5-HT2 and 5-HT3 receptors and may, in some cases, reverse sexual dysfunction induced by SSRIs by the same mechanism.<a href="#cite_note-pmid18278806-164">[164]</a> <a href="/wiki/Bupropion" title="Bupropion">Bupropion</a>, a weak NDRI and nicotinic antagonist, may be useful in treating reduced libido as a result of <a href="/wiki/SSRI" class="mw-redirect" title="SSRI">SSRI</a> treatment.<a href="#cite_note-Schwasinger-Schmidt2018-165">[165]</a> <div class="mw-heading mw-heading3"><h3 id="Emotional_blunting">Emotional blunting</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=23" title="Edit section: Emotional blunting">edit</a>]</div> Certain antidepressants may cause <a href="/wiki/Emotional_blunting" class="mw-redirect" title="Emotional blunting">emotional blunting</a>, characterized by a reduced intensity of both positive and negative emotions as well as symptoms of <a href="/wiki/Apathy" title="Apathy">apathy</a>, <a href="/wiki/Psychological_indifference" class="mw-redirect" title="Psychological indifference">indifference</a>, and <a href="/wiki/Amotivational_syndrome" title="Amotivational syndrome">amotivation</a>.<a href="#cite_note-pmid34908941-166">[166]</a><a href="#cite_note-pmid34970173-167">[167]</a><a href="#cite_note-pmid15330228-168">[168]</a><a href="#cite_note-pmid21103140-169">[169]</a><a href="#cite_note-pmid19721109-170">[170]</a><a href="#cite_note-pmid28628765-171">[171]</a><a href="#cite_note-pmid29866014-172">[172]</a><a href="#cite_note-pmid35346413-173">[173]</a><a href="#cite_note-pmid11436958-174">[174]</a> It may be experienced as either beneficial or detrimental depending on the situation.<a href="#cite_note-pmid26407780-175">[175]</a> This side effect has been particularly associated with serotonergic antidepressants like SSRIs and SNRIs but may be less with atypical antidepressants like bupropion, <a href="/wiki/Agomelatine" title="Agomelatine">agomelatine</a>, and <a href="/wiki/Vortioxetine" title="Vortioxetine">vortioxetine</a>.<a href="#cite_note-pmid34970173-167">[167]</a><a href="#cite_note-pmid35346413-173">[173]</a><a href="#cite_note-pmid23823799-176">[176]</a><a href="#cite_note-pmid33516560-177">[177]</a> Higher doses of antidepressants seem to be more likely to produce emotional blunting than lower doses.<a href="#cite_note-pmid34970173-167">[167]</a> Emotional blunting can be decreased by reducing dosage, discontinuing the medication, or switching to a different antidepressant that may have less propensity for causing this side effect.<a href="#cite_note-pmid34970173-167">[167]</a> <div class="mw-heading mw-heading3"><h3 id="Changes_in_weight">Changes in weight</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=24" title="Edit section: Changes in weight">edit</a>]</div> Changes in appetite or weight are common among antidepressants but are largely drug-dependent and related to which neurotransmitters they affect. Mirtazapine and <a href="/wiki/Paroxetine" title="Paroxetine">paroxetine</a>, for example, may be associated with weight gain and/or increased appetite,<a href="#cite_note-Stimmel-178">[178]</a><a href="#cite_note-179">[179]</a><a href="#cite_note-autogenerated1032-180">[180]</a> while others (such as bupropion and <a href="/wiki/Venlafaxine" title="Venlafaxine">venlafaxine</a>) achieve the opposite effect.<a href="#cite_note-Bupropion_weight-181">[181]</a><a href="#cite_note-182">[182]</a> The <a href="/wiki/Antihistamine" title="Antihistamine">antihistaminic</a> properties of certain TCA- and TeCA-class antidepressants have been shown to contribute to the common side effects of increased appetite and weight gain associated with these classes of medication. <div class="mw-heading mw-heading3"><h3 id="Bone_loss">Bone loss</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=25" title="Edit section: Bone loss">edit</a>]</div> A 2021 nationwide <a href="/wiki/Cohort_study" title="Cohort study">cohort study</a> in South Korea observed a link between SSRI use and bone loss, particularly in recent users. The study also stressed the need of further research to better understand these effects.<a href="#cite_note-183">[183]</a> A 2012 review found that SSRIs along with tricyclic antidepressants were associated with a significant increase in the risk of osteoporotic fractures, peaking in the months after initiation, and moving back towards baseline during the year after treatment was stopped. These effects exhibited a <a href="/wiki/Dose%E2%80%93response_relationship" title="Dose–response relationship">dose–response relationship</a> within SSRIs which varied between different drugs of that class.<a href="#cite_note-184">[184]</a> A 2018 meta-analysis of 11 small studies found a reduction in bone density of the lumbar spine in SSRI users which affected older people the most.<a href="#cite_note-185">[185]</a> <div class="mw-heading mw-heading3"><h3 id="Risk_of_death">Risk of death</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=26" title="Edit section: Risk of death">edit</a>]</div> A 2017 <a href="/wiki/Meta-analysis" title="Meta-analysis">meta-analysis</a> found that antidepressants were associated with a significantly increased <a href="/wiki/Mortality_rate" title="Mortality rate">risk of death</a> (+33%) and new <a href="/wiki/Cardiovascular_complication" class="mw-redirect" title="Cardiovascular complication">cardiovascular complications</a> (+14%) in the general population.<a href="#cite_note-pmid28903117-186">[186]</a> Conversely, risks were not greater in people with existing <a href="/wiki/Cardiovascular_disease" title="Cardiovascular disease">cardiovascular disease</a>.<a href="#cite_note-pmid28903117-186">[186]</a> <div class="mw-heading mw-heading3"><h3 id="Discontinuation_syndrome">Discontinuation syndrome</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=27" title="Edit section: Discontinuation syndrome">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Antidepressant_discontinuation_syndrome" title="Antidepressant discontinuation syndrome">Antidepressant discontinuation syndrome</a></div> Antidepressant discontinuation syndrome, also called antidepressant withdrawal syndrome, is a condition that can occur following the interruption, reduction, or <a href="/wiki/Medication_discontinuation" title="Medication discontinuation">discontinuation</a> of antidepressant medication.<a href="#cite_note-War2006-187">[187]</a> The symptoms may include <a href="/wiki/Flu-like_symptoms" class="mw-redirect" title="Flu-like symptoms">flu-like symptoms</a>, trouble sleeping, nausea, poor balance, sensory changes, and <a href="/wiki/Anxiety" title="Anxiety">anxiety</a>.<a href="#cite_note-War2006-187">[187]</a><a href="#cite_note-Gab2017-13">[13]</a><a href="#cite_note-Dav2018-188">[188]</a> The problem usually begins within three days and may last for several months.<a href="#cite_note-War2006-187">[187]</a><a href="#cite_note-Dav2018-188">[188]</a> Rarely <a href="/wiki/Psychosis" title="Psychosis">psychosis</a> may occur.<a href="#cite_note-War2006-187">[187]</a> A discontinuation syndrome can occur after stopping any antidepressant including <a href="/wiki/Selective_serotonin_reuptake_inhibitor" title="Selective serotonin reuptake inhibitor">selective serotonin reuptake inhibitors</a> (SSRIs), <a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitor" title="Serotonin–norepinephrine reuptake inhibitor">serotonin–norepinephrine reuptake inhibitors</a> (SNRIs), and <a href="/wiki/Tricyclic_antidepressants" class="mw-redirect" title="Tricyclic antidepressants">tricyclic antidepressants</a> (TCAs).<a href="#cite_note-War2006-187">[187]</a><a href="#cite_note-Gab2017-13">[13]</a> The risk is greater among those who have taken the medication for longer and when the medication in question has a short <a href="/wiki/Half-life" title="Half-life">half-life</a>.<a href="#cite_note-War2006-187">[187]</a> The underlying reason for its occurrence is unclear.<a href="#cite_note-War2006-187">[187]</a> The diagnosis is based on the symptoms.<a href="#cite_note-War2006-187">[187]</a> Methods of prevention include gradually decreasing the dose among those who wish to stop, though it is possible for symptoms to occur with tapering.<a href="#cite_note-War2006-187">[187]</a><a href="#cite_note-Wil2015-12">[12]</a><a href="#cite_note-Dav2018-188">[188]</a> Treatment may include restarting the medication and slowly decreasing the dose.<a href="#cite_note-War2006-187">[187]</a> People may also be switched to the long-acting antidepressant <a href="/wiki/Fluoxetine" title="Fluoxetine">fluoxetine</a>, which can then be gradually decreased.<a href="#cite_note-Wil2015-12">[12]</a> Approximately 20–50% of people who suddenly stop an antidepressant develop an antidepressant discontinuation syndrome.<a href="#cite_note-War2006-187">[187]</a><a href="#cite_note-Gab2017-13">[13]</a><a href="#cite_note-Dav2018-188">[188]</a> The condition is generally not serious.<a href="#cite_note-War2006-187">[187]</a> Though about half of people with symptoms describe them as severe.<a href="#cite_note-Dav2018-188">[188]</a> Some restart antidepressants due to the severity of the symptoms.<a href="#cite_note-Dav2018-188">[188]</a> <div class="mw-heading mw-heading2"><h2 id="Pharmacology">Pharmacology</h2>[<a href="/w/index.php?title=Antidepressant&action=edit&section=28" title="Edit section: Pharmacology">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Pharmacology_of_antidepressants" title="Pharmacology of antidepressants">Pharmacology of antidepressants</a></div> Antidepressants act via a large number of different <a href="/wiki/Mechanism_of_action" title="Mechanism of action">mechanisms of action</a>.<a href="#cite_note-Fasipe2018-189">[189]</a><a href="#cite_note-pmid35714379-190">[190]</a><a href="#cite_note-Stahl2020-191">[191]</a> This includes <a href="/wiki/Serotonin_reuptake_inhibition" class="mw-redirect" title="Serotonin reuptake inhibition">serotonin reuptake inhibition</a> (SSRIs, SNRIs, TCAs, vilazodone, vortioxetine), <a href="/wiki/Norepinephrine_reuptake_inhibition" class="mw-redirect" title="Norepinephrine reuptake inhibition">norepinephrine reuptake inhibition</a> (NRIs, SNRIs, TCAs), <a href="/wiki/Dopamine_reuptake_inhibition" class="mw-redirect" title="Dopamine reuptake inhibition">dopamine reuptake inhibition</a> (bupropion, amineptine, nomifensine), direct <a href="/wiki/Receptor_modulation" class="mw-redirect" title="Receptor modulation">modulation</a> of <a href="/wiki/Monoamine_receptor" title="Monoamine receptor">monoamine receptors</a> (vilazodone, vortioxetine, SARIs, agomelatine, TCAs, TeCAs, antipsychotics), <a href="/wiki/Monoamine_oxidase_inhibition" class="mw-redirect" title="Monoamine oxidase inhibition">monoamine oxidase inhibition</a> (MAOIs), and <a href="/wiki/NMDA_receptor_antagonism" class="mw-redirect" title="NMDA receptor antagonism">NMDA receptor antagonism</a> (ketamine, esketamine, dextromethorphan), among others (e.g., brexanolone, tianeptine).<a href="#cite_note-Fasipe2018-189">[189]</a><a href="#cite_note-pmid35714379-190">[190]</a><a href="#cite_note-Stahl2020-191">[191]</a> Some antidepressants also have additional actions, like <a href="/wiki/Sigma_receptor" title="Sigma receptor">sigma receptor</a> modulation (certain SSRIs, TCAs, dextromethorphan) and <a href="/wiki/Receptor_antagonism" class="mw-redirect" title="Receptor antagonism">antagonism</a> of <a href="/wiki/Histamine" title="Histamine">histamine</a> <a href="/wiki/H1_receptor" class="mw-redirect" title="H1 receptor">H1</a> and <a href="/wiki/Muscarinic_acetylcholine_receptor" title="Muscarinic acetylcholine receptor">muscarinic acetylcholine receptors</a> (TCAs, TeCAs).<a href="#cite_note-BolandKeller2008-192">[192]</a><a href="#cite_note-Stahl2020-191">[191]</a> <table class="wikitable" style="font-size:small;"> <caption>Mechanisms of action of major antidepressant classes<a href="#cite_note-Fasipe2018-189">[189]</a><a href="#cite_note-ParkShen2023-193">[193]</a> </caption> <tbody><tr> <th>Class</th> <th>Action(s)</th> <th>Examples</th> <th>Introduced </th></tr> <tr> <td><a href="/wiki/Opioid" title="Opioid">Opioids</a> (mostly no longer used)<a href="#cite_note-SaxenaBodkin2019-194">[194]</a><a href="#cite_note-NishioLindsleyBender2024-195">[195]</a></td> <td><a href="/wiki/%CE%9C-Opioid_receptor" class="mw-redirect" title="Μ-Opioid receptor">μ-Opioid receptor</a> <a href="/wiki/Agonist" title="Agonist">agonism</a></td> <td><a href="/wiki/Codeine" title="Codeine">Codeine</a> • <a href="/wiki/Heroin" title="Heroin">Heroin</a> • <a href="/wiki/Morphine" title="Morphine">Morphine</a> • <a href="/wiki/Opium" title="Opium">Opium</a> • <a href="/wiki/Tianeptine" title="Tianeptine">Tianeptine</a> (1983)</td> <td>1800s </td></tr> <tr> <td><a href="/wiki/Amphetamine-type_stimulant" class="mw-redirect" title="Amphetamine-type stimulant">Amphetamine psychostimulants</a> (mostly no longer used)<a href="#cite_note-Rasmussen2006-196">[196]</a><a href="#cite_note-Ciccarone2011-197">[197]</a><a href="#cite_note-Rasmussen2015-198">[198]</a><a href="#cite_note-HealSmithGosden2013-199">[199]</a></td> <td><a href="/wiki/Norepinephrine_releasing_agent" title="Norepinephrine releasing agent">Norepinephrine release induction</a> • <a href="/wiki/Dopamine_releasing_agent" title="Dopamine releasing agent">Dopamine release induction</a></td> <td><a href="/wiki/Amphetamine" title="Amphetamine">Amphetamine</a> • <a href="/wiki/Dextroamphetamine" title="Dextroamphetamine">Dextroamphetamine</a> • <a href="/wiki/Methamphetamine" title="Methamphetamine">Methamphetamine</a></td> <td>1930s </td></tr> <tr> <td><a href="/wiki/Monoamine_oxidase_inhibitor" title="Monoamine oxidase inhibitor">Monoamine oxidase inhibitors</a> (MAOIs)</td> <td><a href="/wiki/Monoamine_oxidase" title="Monoamine oxidase">Monoamine oxidase</a> <a href="/wiki/Enzyme_inhibitor" title="Enzyme inhibitor">inhibition</a> • Other actions in some cases</td> <td><a href="/wiki/Iproniazid" title="Iproniazid">Iproniazid</a> • <a href="/wiki/Isocarboxazid" title="Isocarboxazid">Isocarboxazid</a> • <a href="/wiki/Isoniazid" title="Isoniazid">Isoniazid</a> • <a href="/wiki/Moclobemide" title="Moclobemide">Moclobemide</a> (1989) • <a href="/wiki/Nialamide" title="Nialamide">Nialamide</a> • <a href="/wiki/Phenelzine" title="Phenelzine">Phenelzine</a> • <a href="/wiki/Selegiline" title="Selegiline">Selegiline</a> (1977/2006) • <a href="/wiki/Tranylcypromine" title="Tranylcypromine">Tranylcypromine</a></td> <td>1950s </td></tr> <tr> <td><a href="/wiki/Tricyclic_antidepressant" title="Tricyclic antidepressant">Tricyclic antidepressants</a> (TCAs)</td> <td><a href="/wiki/Serotonin_reuptake_inhibitor" title="Serotonin reuptake inhibitor">Serotonin reuptake inhibition</a> • <a href="/wiki/Norepinephrine_reuptake_inhibitor" title="Norepinephrine reuptake inhibitor">Norepinephrine reuptake inhibition</a> • <a href="/wiki/Serotonin_receptor_antagonist" title="Serotonin receptor antagonist">Serotonin receptor antagonism</a> • <a href="/wiki/Adrenergic_receptor_antagonist" class="mw-redirect" title="Adrenergic receptor antagonist">Adrenergic receptor antagonism</a> • <a href="/wiki/H1_antagonist" title="H1 antagonist">Histamine H1 receptor antagonism</a> • <a href="/wiki/Muscarinic_antagonist" title="Muscarinic antagonist">Muscarinic acetylcholine receptor antagonism</a> • Other actions</td> <td><a href="/wiki/Amitriptyline" title="Amitriptyline">Amitriptyline</a> • <a href="/wiki/Butriptyline" title="Butriptyline">Butriptyline</a> • <a href="/wiki/Clomipramine" title="Clomipramine">Clomipramine</a> • <a href="/wiki/Desipramine" title="Desipramine">Desipramine</a> • <a href="/wiki/Dosulepin" title="Dosulepin">Dosulepin (dothiepin)</a> • <a href="/wiki/Doxepin" title="Doxepin">Doxepin</a> • <a href="/wiki/Imipramine" title="Imipramine">Imipramine</a> • <a href="/wiki/Iprindole" title="Iprindole">Iprindole</a> • <a href="/wiki/Lofepramine" title="Lofepramine">Lofepramine</a> • <a href="/wiki/Nortriptyline" title="Nortriptyline">Nortriptyline</a> • <a href="/wiki/Protriptyline" title="Protriptyline">Protriptyline</a> • <a href="/wiki/Trimipramine" title="Trimipramine">Trimipramine</a></td> <td>1950s </td></tr> <tr> <td><a href="/wiki/Tetracyclic_antidepressant" title="Tetracyclic antidepressant">Tetracyclic antidepressants</a> (TeCAs)</td> <td><a href="/wiki/Serotonin_reuptake_inhibitor" title="Serotonin reuptake inhibitor">Serotonin reuptake inhibition</a> • <a href="/wiki/Norepinephrine_reuptake_inhibitor" title="Norepinephrine reuptake inhibitor">Norepinephrine reuptake inhibition</a> • <a href="/wiki/Serotonin_receptor_antagonist" title="Serotonin receptor antagonist">Serotonin receptor antagonism</a> • <a href="/wiki/Adrenergic_receptor_antagonist" class="mw-redirect" title="Adrenergic receptor antagonist">Adrenergic receptor antagonism</a> • <a href="/wiki/H1_antagonist" title="H1 antagonist">Histamine H1 receptor antagonism</a> • <a href="/wiki/Muscarinic_antagonist" title="Muscarinic antagonist">Muscarinic acetylcholine receptor antagonism</a> • Other actions</td> <td><a href="/wiki/Amoxapine" title="Amoxapine">Amoxapine</a> • <a href="/wiki/Maprotiline" title="Maprotiline">Maprotiline</a> • <a href="/wiki/Mianserin" title="Mianserin">Mianserin</a> • <a href="/wiki/Mirtazapine" title="Mirtazapine">Mirtazapine</a> • <a href="/wiki/Setiptiline" title="Setiptiline">Setiptiline</a></td> <td>1970s </td></tr> <tr> <td><a href="/wiki/Norepinephrine_reuptake_inhibitor" title="Norepinephrine reuptake inhibitor">Norepinephrine reuptake inhibitors</a> (NRIs)</td> <td><a href="/wiki/Norepinephrine_reuptake_inhibitor" title="Norepinephrine reuptake inhibitor">Norepinephrine reuptake inhibition</a></td> <td><a href="/wiki/Atomoxetine" title="Atomoxetine">Atomoxetine</a> (off-label) • <a href="/wiki/Teniloxazine" title="Teniloxazine">Teniloxazine</a> • <a href="/wiki/Reboxetine" title="Reboxetine">Reboxetine</a> • <a href="/wiki/Viloxazine" title="Viloxazine">Viloxazine</a></td> <td>1970s </td></tr> <tr> <td><a href="/wiki/Norepinephrine%E2%80%93dopamine_reuptake_inhibitor" title="Norepinephrine–dopamine reuptake inhibitor">Norepinephrine–dopamine reuptake inhibitors</a> (NDRIs)</td> <td><a href="/wiki/Norepinephrine_reuptake_inhibitor" title="Norepinephrine reuptake inhibitor">Norepinephrine reuptake inhibition</a> • <a href="/wiki/Dopamine_reuptake_inhibitor" title="Dopamine reuptake inhibitor">Dopamine reuptake inhibition</a></td> <td><a href="/wiki/Amineptine" title="Amineptine">Amineptine</a> • <a href="/wiki/Bupropion" title="Bupropion">Bupropion</a> • <a href="/wiki/Methylphenidate" title="Methylphenidate">Methylphenidate</a> (off-label) • <a href="/wiki/Nomifensine" title="Nomifensine">Nomifensine</a></td> <td>1970s </td></tr> <tr> <td><a href="/wiki/Serotonin_antagonists_and_reuptake_inhibitors" class="mw-redirect" title="Serotonin antagonists and reuptake inhibitors">Serotonin antagonists and reuptake inhibitors</a> (SARIs)</td> <td><a href="/wiki/Serotonin_receptor_antagonist" title="Serotonin receptor antagonist">Serotonin receptor antagonism</a> • <a href="/wiki/Adrenergic_receptor_antagonist" class="mw-redirect" title="Adrenergic receptor antagonist">Adrenergic receptor antagonism</a> • Weak <a href="/wiki/Monoamine_reuptake_inhibitor" title="Monoamine reuptake inhibitor">monoamine reuptake inhibition</a> • Other actions</td> <td><a href="/wiki/Etoperidone" title="Etoperidone">Etoperidone</a> • <a href="/wiki/Nefazodone" title="Nefazodone">Nefazodone</a> • <a href="/wiki/Trazodone" title="Trazodone">Trazodone</a></td> <td>1980s </td></tr> <tr> <td><a href="/wiki/Selective_serotonin_reuptake_inhibitor" title="Selective serotonin reuptake inhibitor">Selective serotonin reuptake inhibitors</a> (SSRIs)</td> <td><a href="/wiki/Serotonin_reuptake_inhibitor" title="Serotonin reuptake inhibitor">Serotonin reuptake inhibition</a></td> <td><a href="/wiki/Citalopram" title="Citalopram">Citalopram</a> • <a href="/wiki/Escitalopram" title="Escitalopram">Escitalopram</a> • <a href="/wiki/Fluoxetine" title="Fluoxetine">Fluoxetine</a> • <a href="/wiki/Fluvoxamine" title="Fluvoxamine">Fluvoxamine</a> • <a href="/wiki/Indalpine" title="Indalpine">Indalpine</a> • <a href="/wiki/Paroxetine" title="Paroxetine">Paroxetine</a> • <a href="/wiki/Sertraline" title="Sertraline">Sertraline</a> • <a href="/wiki/Zimelidine" title="Zimelidine">Zimelidine</a></td> <td>1980s </td></tr> <tr> <td><a href="/wiki/Serotonin" title="Serotonin">Serotonin</a> <a href="/wiki/5-HT1A_receptor" title="5-HT1A receptor">5-HT1A receptor</a> <a href="/wiki/Agonist" title="Agonist">agonists</a> (<a href="/wiki/Azapirone" title="Azapirone">azapirones</a>)</td> <td><a href="/wiki/Serotonin" title="Serotonin">Serotonin</a> <a href="/wiki/5-HT1A_receptor" title="5-HT1A receptor">5-HT1A receptor</a> <a href="/wiki/Partial_agonist" title="Partial agonist">partial agonism</a> • Other actions</td> <td><a href="/wiki/Buspirone" title="Buspirone">Buspirone</a> (off-label) • <a href="/wiki/Gepirone" title="Gepirone">Gepirone</a> • <a href="/wiki/Tandospirone" title="Tandospirone">Tandospirone</a></td> <td>1980s </td></tr> <tr> <td><a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitor" title="Serotonin–norepinephrine reuptake inhibitor">Serotonin–norepinephrine reuptake inhibitors</a> (SNRIs)</td> <td><a href="/wiki/Serotonin_reuptake_inhibitor" title="Serotonin reuptake inhibitor">Serotonin reuptake inhibition</a> • <a href="/wiki/Norepinephrine_reuptake_inhibitor" title="Norepinephrine reuptake inhibitor">Norepinephrine reuptake inhibition</a></td> <td><a href="/wiki/Desvenlafaxine" title="Desvenlafaxine">Desvenlafaxine</a> • <a href="/wiki/Duloxetine" title="Duloxetine">Duloxetine</a> • <a href="/wiki/Levomilnacipran" title="Levomilnacipran">Levomilnacipran</a> • <a href="/wiki/Milnacipran" title="Milnacipran">Milnacipran</a> (off-label) • <a href="/wiki/Venlafaxine" title="Venlafaxine">Venlafaxine</a></td> <td>1990s </td></tr> <tr> <td><a href="/wiki/Serotonin_modulators_and_stimulators" class="mw-redirect" title="Serotonin modulators and stimulators">Serotonin modulators and stimulators</a> (SMSs)</td> <td><a href="/wiki/Serotonin_reuptake_inhibitor" title="Serotonin reuptake inhibitor">Serotonin reuptake inhibition</a> • <a href="/wiki/Serotonin_receptor" class="mw-redirect" title="Serotonin receptor">Serotonin receptor</a> <a href="/wiki/Receptor_modulator" title="Receptor modulator">modulation</a></td> <td><a href="/wiki/Vilazodone" title="Vilazodone">Vilazodone</a> • <a href="/wiki/Vortioxetine" title="Vortioxetine">Vortioxetine</a></td> <td>2000s </td></tr> <tr> <td><a href="/wiki/Atypical_antipsychotic" title="Atypical antipsychotic">Atypical antipsychotics</a></td> <td><a href="/wiki/Serotonin_receptor" class="mw-redirect" title="Serotonin receptor">Serotonin receptor</a> <a href="/wiki/Receptor_modulation" class="mw-redirect" title="Receptor modulation">modulation</a> • <a href="/wiki/Dopamine_receptor" title="Dopamine receptor">Dopamine receptor</a> <a href="/wiki/Receptor_modulator" title="Receptor modulator">modulation</a> • Other actions</td> <td><a href="/wiki/Amisulpride" title="Amisulpride">Amisulpride</a> • <a href="/wiki/Aripiprazole" title="Aripiprazole">Aripiprazole</a> • <a href="/wiki/Brexpiprazole" title="Brexpiprazole">Brexpiprazole</a> • <a href="/wiki/Lumateperone" title="Lumateperone">Lumateperone</a> • <a href="/wiki/Lurasidone" title="Lurasidone">Lurasidone</a> • <a href="/wiki/Olanzapine" title="Olanzapine">Olanzapine</a> • <a href="/wiki/Quetiapine" title="Quetiapine">Quetiapine</a> • <a href="/wiki/Risperidone" title="Risperidone">Risperidone</a> (off-label) • <a href="/wiki/Sulpiride" title="Sulpiride">Sulpiride</a></td> <td>2000s </td></tr> <tr> <td><a href="/wiki/NMDA_receptor_antagonist" title="NMDA receptor antagonist">NMDA receptor antagonists</a></td> <td><a href="/wiki/NMDA_receptor_antagonism" class="mw-redirect" title="NMDA receptor antagonism">NMDA receptor antagonism</a> • Possibly other actions</td> <td><a href="/wiki/Dextromethorphan/bupropion" title="Dextromethorphan/bupropion">Dextromethorphan/bupropion</a> • <a href="/wiki/Esketamine" title="Esketamine">Esketamine</a> • <a href="/wiki/Ketamine" title="Ketamine">Ketamine</a> (off-label)</td> <td>2010s </td></tr> <tr> <td><a href="/wiki/Neurosteroid" title="Neurosteroid">Neurosteroid</a>-type <a href="/wiki/GABAA_receptor_positive_allosteric_modulator" title="GABAA receptor positive allosteric modulator">GABAA receptor positive allosteric modulators</a></td> <td><a href="/wiki/GABAA_receptor_positive_allosteric_modulator" title="GABAA receptor positive allosteric modulator">GABAA receptor positive allosteric modulation</a></td> <td><a href="/wiki/Brexanolone" class="mw-redirect" title="Brexanolone">Brexanolone</a> • <a href="/wiki/Zuranolone" title="Zuranolone">Zuranolone</a></td> <td>2010s </td></tr> <tr> <td><a href="/wiki/Serotonin%E2%80%93norepinephrine%E2%80%93dopamine_reuptake_inhibitor" title="Serotonin–norepinephrine–dopamine reuptake inhibitor">Serotonin–norepinephrine–dopamine reuptake inhibitors</a></td> <td><a href="/wiki/Serotonin_reuptake_inhibitor" title="Serotonin reuptake inhibitor">Serotonin reuptake inhibition</a> • <a href="/wiki/Norepinephrine_reuptake_inhibitor" title="Norepinephrine reuptake inhibitor">Norepinephrine reuptake inhibition</a> • <a href="/wiki/Dopamine_reuptake_inhibitor" title="Dopamine reuptake inhibitor">Dopamine reuptake inhibition</a></td> <td><a href="/wiki/Toludesvenlafaxine" class="mw-redirect" title="Toludesvenlafaxine">Toludesvenlafaxine</a></td> <td>2020s </td></tr> <tr> <td><a href="/wiki/Atypical_antidepressant" title="Atypical antidepressant">Other agents</a></td> <td>Various/mixed actions</td> <td><a href="/wiki/%CE%91-Methyltryptamine" title="Α-Methyltryptamine">α-Methyltryptamine</a> • <a href="/wiki/Ademetionine" class="mw-redirect" title="Ademetionine">Ademetionine (SAMe)</a> • <a href="/wiki/Agomelatine" title="Agomelatine">Agomelatine</a> • <a href="/wiki/D-Phenylalanine" title="D-Phenylalanine">D-Phenylalanine</a> • <a href="/wiki/Etryptamine" class="mw-redirect" title="Etryptamine">Etryptamine</a> • <a href="/wiki/Hypericum_perforatum" title="Hypericum perforatum">Hypericum perforatum (St John's wort)</a> <a href="/wiki/Indeloxazine" title="Indeloxazine">Indeloxazine</a> • <a href="/wiki/Lithium_(medication)" title="Lithium (medication)">Lithium</a> (off-label) • <a href="/wiki/Medifoxamine" title="Medifoxamine">Medifoxamine</a> • <a href="/wiki/Opipramol" title="Opipramol">Opipramol</a> • <a href="/wiki/Oxaflozane" title="Oxaflozane">Oxaflozane</a> • <a href="/wiki/Oxitriptan" title="Oxitriptan">Oxitriptan (5-HTP)</a> • <a href="/wiki/Pivagabine" title="Pivagabine">Pivagabine</a> • <a href="/wiki/Thyroid_hormone" class="mw-redirect" title="Thyroid hormone">Thyroid hormone</a> (off-label) • <a href="/wiki/Tiazesim" title="Tiazesim">Tiazesim</a> • <a href="/wiki/Tofenacin" title="Tofenacin">Tofenacin</a> • <a href="/wiki/Tryptophan" title="Tryptophan">Tryptophan</a></td> <td>Various </td></tr> <tr class="sortbottom"> <td colspan="4" style="width: 1px; background-color:#eaecf0; text-align: center;">Notes: (1) Opioids and amphetamines largely ceased being used by the 1950s with the introduction of modern antidepressants. (2) Some antidepressants can also have alternative classifications, such as <a href="/wiki/Mirtazapine" title="Mirtazapine">mirtazapine</a> being a "<a href="/wiki/Noradrenergic_and_specific_serotonergic_antidepressant" title="Noradrenergic and specific serotonergic antidepressant">noradrenergic and specific serotonergic antidepressant</a>" (NaSSA) or <a href="/wiki/Moclobemide" title="Moclobemide">moclobemide</a> being a "<a href="/wiki/Reversible_inhibitor_of_monoamine_oxidase_A" class="mw-redirect" title="Reversible inhibitor of monoamine oxidase A">reversible inhibitor of monoamine oxidase A</a>" (RIMA). (3) See <a href="/wiki/List_of_antidepressants" title="List of antidepressants">list of antidepressants</a> for a complete list of approved/marketed antidepressants. (4) See <a href="/wiki/List_of_investigational_antidepressants" title="List of investigational antidepressants">list of investigational antidepressants</a> for an extensive list of modern investigational antidepressants (including discontinued agents). </td></tr></tbody></table> The earliest and most widely known <a href="/wiki/Scientific_theory" title="Scientific theory">scientific theory</a> of antidepressant action is the <a href="/wiki/Monoamine_hypothesis" class="mw-redirect" title="Monoamine hypothesis">monoamine hypothesis</a>, which can be traced back to the 1950s and 1960s.<a href="#cite_note-GG-200">[200]</a><a href="#cite_note-pmid12953623-201">[201]</a> This theory states that depression is due to an imbalance, most often a deficiency, of the <a href="/wiki/Monoamine_neurotransmitter" title="Monoamine neurotransmitter">monoamine neurotransmitters</a>, namely <a href="/wiki/Serotonin" title="Serotonin">serotonin</a>, <a href="/wiki/Norepinephrine" title="Norepinephrine">norepinephrine</a>, and/or <a href="/wiki/Dopamine" title="Dopamine">dopamine</a>.<a href="#cite_note-GG-200">[200]</a><a href="#cite_note-pmid12953623-201">[201]</a> However, serotonin in particular has been implicated, as in the serotonin hypothesis of depression.<a href="#cite_note-pmid35854107-202">[202]</a> The monoamine hypothesis was originally proposed based on observations that <a href="/wiki/Reserpine" title="Reserpine">reserpine</a>, a drug which depletes the monoamine neurotransmitters, produced depressive effects in people,<a href="#cite_note-pmid12953623-201">[201]</a> and that certain <a href="/wiki/Hydrazine" title="Hydrazine">hydrazine</a> <a href="/wiki/Antituberculosis_agent" class="mw-redirect" title="Antituberculosis agent">antituberculosis agents</a> like <a href="/wiki/Iproniazid" title="Iproniazid">iproniazid</a>, which <a href="/wiki/Monoamine_oxidase_inhibitor" title="Monoamine oxidase inhibitor">prevent the breakdown of monoamine neurotransmitters</a>, produced apparent antidepressant effects.<a href="#cite_note-GG-200">[200]</a> Most currently marketed antidepressants, which are <a href="/wiki/Monoaminergic" title="Monoaminergic">monoaminergic</a> in their actions, are theoretically consistent with the monoamine hypothesis.<a href="#cite_note-GG-200">[200]</a> Despite the widespread nature of the monoamine hypothesis, it has a number of limitations: for one, all monoaminergic antidepressants have a delayed onset of action of at least a week; and secondly, many people with depression do not respond to monoaminergic antidepressants.<a href="#cite_note-Infl-203">[203]</a><a href="#cite_note-glut-204">[204]</a> A number of alternative hypotheses have been proposed, including hypotheses involving <a href="/wiki/Glutamate" class="mw-redirect" title="Glutamate">glutamate</a>, <a href="/wiki/Neurogenesis" title="Neurogenesis">neurogenesis</a>, <a href="/wiki/Epigenetics" title="Epigenetics">epigenetics</a>, <a href="/wiki/Cortisol" title="Cortisol">cortisol</a> <a href="/wiki/Hypersecretion" class="mw-redirect" title="Hypersecretion">hypersecretion</a>, and <a href="/wiki/Inflammation" title="Inflammation">inflammation</a>, among others.<a href="#cite_note-Infl-203">[203]</a><a href="#cite_note-glut-204">[204]</a><a href="#cite_note-Epig-205">[205]</a><a href="#cite_note-Epig2-206">[206]</a> In 2022, a major systematic <a href="/wiki/Umbrella_review" title="Umbrella review">umbrella review</a> by <a href="/wiki/Joanna_Moncrieff" title="Joanna Moncrieff">Joanna Moncrieff</a> and colleagues showed that the serotonin theory of depression was not supported by evidence from a wide variety of areas.<a href="#cite_note-pmid35854107-202">[202]</a> The authors concluded that there is no association between serotonin and depression, and that there is no evidence that strongly supports the theory that depression is caused by low serotonin activity or concentrations.<a href="#cite_note-pmid35854107-202">[202]</a> Other literature had described the lack of support for the theory previously.<a href="#cite_note-pmid16268734-106">[106]</a><a href="#cite_note-LacasseLeo2015-107">[107]</a><a href="#cite_note-AngHorowitzMoncrieff2022-109">[109]</a> In many of the expert responses to the review, it was stated that the monoamine hypothesis had already long been abandoned by psychiatry.<a href="#cite_note-ScienceMediaCentre2022-207">[207]</a><a href="#cite_note-MadInAmerica2022-208">[208]</a> This is in spite of about 90% of the general public in Western countries believing the theory to be true and many in the field of psychiatry continuing to promote the theory up to recent times.<a href="#cite_note-MadInAmerica2022-208">[208]</a><a href="#cite_note-AngHorowitzMoncrieff2022-109">[109]</a> In addition to the serotonin umbrella review, reviews have found that <a href="/wiki/Reserpine" title="Reserpine">reserpine</a>, a drug that depletes the monoamine neurotransmitters—including serotonin, norepinephrine, and dopamine—shows no consistent evidence of producing depressive effects.<a href="#cite_note-pmid12953623-201">[201]</a><a href="#cite_note-pmid36000248-209">[209]</a> Instead, findings of reserpine and mood are highly mixed, with similar proportions of studies finding that it has no influence on mood, produces depressive effects, or actually has antidepressant effects.<a href="#cite_note-pmid36000248-209">[209]</a> In relation to this, the general monoamine hypothesis, as opposed to only the serotonin theory of depression, likewise does not appear to be well-supported by evidence.<a href="#cite_note-pmid12953623-201">[201]</a><a href="#cite_note-pmid36000248-209">[209]</a><a href="#cite_note-AngHorowitzMoncrieff2022-109">[109]</a> The serotonin and monoamine hypotheses of depression have been heavily promoted by the <a href="/wiki/Pharmaceutical_industry" title="Pharmaceutical industry">pharmaceutical industry</a> (e.g., in <a href="/wiki/Advertisement" class="mw-redirect" title="Advertisement">advertisements</a>) and by the psychiatric profession at large despite the lack of evidence in support of them.<a href="#cite_note-pmid16268734-106">[106]</a><a href="#cite_note-LacasseLeo2015-107">[107]</a><a href="#cite_note-pmid12953623-201">[201]</a><a href="#cite_note-LeoLacasse2007-210">[210]</a><a href="#cite_note-AngHorowitzMoncrieff2022-109">[109]</a><a href="#cite_note-Lacasse2005-108">[108]</a> In the case of the pharmaceutical industry, this can be attributed to obvious financial incentives, with the theory creating a bias against <a href="/wiki/Non-pharmacological_treatment" class="mw-redirect" title="Non-pharmacological treatment">non-pharmacological treatments</a> for depression.<a href="#cite_note-Lacasse2005-108">[108]</a><a href="#cite_note-pmid16268734-106">[106]</a><a href="#cite_note-LacasseLeo2015-107">[107]</a><a href="#cite_note-pmid12953623-201">[201]</a> An alternative theory for antidepressant action proposed by certain academics such as <a href="/wiki/Irving_Kirsch" title="Irving Kirsch">Irving Kirsch</a> and <a href="/wiki/Joanna_Moncrieff" title="Joanna Moncrieff">Joanna Moncrieff</a> is that they work largely or entirely via <a href="/wiki/Placebo" title="Placebo">placebo</a> mechanisms.<a href="#cite_note-pmid31249537-44">[44]</a><a href="#cite_note-Kirsch2014-102">[102]</a><a href="#cite_note-Kirsch2010-211">[211]</a><a href="#cite_note-pmid35100527-212">[212]</a> This is supported by meta-analyses of <a href="/wiki/Randomized_controlled_trial" title="Randomized controlled trial">randomized controlled trials</a> of antidepressants for depression, which consistently show that placebo groups in trials improve about 80 to 90% as much as antidepressant groups on average<a href="#cite_note-pmid31249537-44">[44]</a><a href="#cite_note-HengartnerPlöderl2018-213">[213]</a> and that antidepressants are only marginally more effective for depression than placebos.<a href="#cite_note-pmid31248914-97">[97]</a><a href="#cite_note-pmid32101579-90">[90]</a><a href="#cite_note-pmid29477251-214">[214]</a><a href="#cite_note-pmid35918097-84">[84]</a><a href="#cite_note-pmid30386270-85">[85]</a> The difference between antidepressants and placebo corresponds to an <a href="/wiki/Effect_size" title="Effect size">effect size</a> (<a href="/wiki/Standardized_mean_difference" class="mw-redirect" title="Standardized mean difference">SMD</a>) of about 0.3, which in turn equates to about a 2- to 3-point additional improvement on the 0–52-point (<a href="/wiki/Hamilton_Depression_Rating_Scale" class="mw-redirect" title="Hamilton Depression Rating Scale">HRSD</a>) and 0–60-point (<a href="/wiki/Montgomery%E2%80%93%C3%85sberg_Depression_Rating_Scale" title="Montgomery–Åsberg Depression Rating Scale">MADRS</a>) <a href="/wiki/Depression_rating_scale" class="mw-redirect" title="Depression rating scale">depression rating scales</a> used in trials.<a href="#cite_note-pmid31248914-97">[97]</a><a href="#cite_note-pmid32101579-90">[90]</a><a href="#cite_note-pmid29477251-214">[214]</a><a href="#cite_note-pmid35918097-84">[84]</a><a href="#cite_note-pmid30386270-85">[85]</a> Differences in effectiveness between different antidepressants are small and not clinically meaningful.<a href="#cite_note-pmid36638223-215">[215]</a><a href="#cite_note-pmid29477251-214">[214]</a> The small advantage of antidepressants over placebo is often <a href="/wiki/Statistically_significant" class="mw-redirect" title="Statistically significant">statistically significant</a> and is the basis for their regulatory approval, but is sufficiently modest that its <a href="/wiki/Clinical_significance" title="Clinical significance">clinical significance</a> is doubtful.<a href="#cite_note-pmid25979317-88">[88]</a><a href="#cite_note-pmid33593736-216">[216]</a><a href="#cite_note-pmid32101579-90">[90]</a><a href="#cite_note-pmid30386270-85">[85]</a> Moreover, the small advantage of antidepressants over placebo may simply be a <a href="/wiki/Methodological_artifact" class="mw-redirect" title="Methodological artifact">methodological artifact</a> caused by <a href="/wiki/Unblinding" class="mw-redirect" title="Unblinding">unblinding</a> due to the <a href="/wiki/Psychoactive" class="mw-redirect" title="Psychoactive">psychoactive</a> effects and <a href="/wiki/Side_effect" title="Side effect">side effects</a> of antidepressants, in turn resulting in enhanced placebo effects and apparent antidepressant efficacy.<a href="#cite_note-pmid31249537-44">[44]</a><a href="#cite_note-pmid30386270-85">[85]</a><a href="#cite_note-Kirsch2014-102">[102]</a> Placebos have been found to modify the activity of several brain regions and to increase levels of dopamine and <a href="/wiki/Endogenous" class="mw-redirect" title="Endogenous">endogenous</a> <a href="/wiki/Opioid" title="Opioid">opioids</a> in the <a href="/wiki/Reward_pathway" class="mw-redirect" title="Reward pathway">reward pathways</a>.<a href="#cite_note-pmid35078210-217">[217]</a><a href="#cite_note-pmid36006479-218">[218]</a><a href="#cite_note-pmid15874901-219">[219]</a> It has been argued by Kirsch that although antidepressants may be used efficaciously for depression as <a href="/wiki/Active_placebo" title="Active placebo">active placebos</a>, they are limited by significant pharmacological <a href="/wiki/Side_effect" title="Side effect">side effects</a> and risks, and therefore <a href="/wiki/Non-pharmaceutical_intervention" class="mw-redirect" title="Non-pharmaceutical intervention">non-pharmacological therapies</a>, such as <a href="/wiki/Psychotherapy" title="Psychotherapy">psychotherapy</a> and lifestyle changes, which can have similar efficacy to antidepressants but do not have their adverse effects, ought to be preferred as treatments in people with depression.<a href="#cite_note-pmid31554608-87">[87]</a> The <a href="/wiki/Placebo_response" class="mw-redirect" title="Placebo response">placebo response</a>, or the improvement in scores in the placebo group in clinical trials, is not only due to the <a href="/wiki/Placebo_effect" class="mw-redirect" title="Placebo effect">placebo effect</a>, but is also due to other phenomena such as <a href="/wiki/Spontaneous_remission" title="Spontaneous remission">spontaneous remission</a> and <a href="/wiki/Regression_to_the_mean" class="mw-redirect" title="Regression to the mean">regression to the mean</a>.<a href="#cite_note-pmid31249537-44">[44]</a><a href="#cite_note-pmid30975717-220">[220]</a> Depression tends to have an episodic course, with people eventually recovering even with no medical intervention, and people tend to seek treatment, as well as enroll in clinical trials, when they are feeling their worst.<a href="#cite_note-Hengartner2022-101">[101]</a><a href="#cite_note-pmid30975717-220">[220]</a> In meta-analyses of trials of depression therapies, Kirsch estimated based on improvement in untreated waiting-list controls that spontaneous remission and regression to the mean only account for about 25% of the improvement in depression scores with antidepressant therapy.<a href="#cite_note-pmid31249537-44">[44]</a><a href="#cite_note-pmid22860015-221">[221]</a><a href="#cite_note-KirschSapirstein1998-222">[222]</a><a href="#cite_note-pmid20170046-223">[223]</a><a href="#cite_note-Hengartner2022-101">[101]</a> However, another academic, <a href="/wiki/Michael_P._Hengartner" title="Michael P. Hengartner">Michael P. Hengartner</a>, has argued and presented evidence that spontaneous remission and regression to the mean might actually account for most of the improvement in depression scores with antidepressants, and that the substantial placebo effect observed in clinical trials might largely be a methodological artifact.<a href="#cite_note-pmid30975717-220">[220]</a> This suggests that antidepressants may be associated with much less genuine treatment benefit, whether due to the placebo effect or to the antidepressant itself, than has been traditionally assumed.<a href="#cite_note-pmid30975717-220">[220]</a> It has been proposed that <a href="/wiki/Psychedelic_drug" title="Psychedelic drug">psychedelics</a> used for therapeutic purposes may act as <a href="/wiki/Active_placebo" title="Active placebo">active</a> "super placebos".<a href="#cite_note-DupuisVeissière2022-224">[224]</a><a href="#cite_note-vanElkYaden2022-225">[225]</a> <div class="mw-heading mw-heading2"><h2 id="Types">Types</h2>[<a href="/w/index.php?title=Antidepressant&action=edit&section=29" title="Edit section: Types">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">See also: <a href="/wiki/List_of_antidepressants" title="List of antidepressants">List of antidepressants</a></div> <div class="mw-heading mw-heading3"><h3 id="Selective_serotonin_reuptake_inhibitors">Selective serotonin reuptake inhibitors</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=30" title="Edit section: Selective serotonin reuptake inhibitors">edit</a>]</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Paroxetine-2D-skeletal.svg" class="mw-file-description"><img alt="refer to caption" src="//upload.wikimedia.org/wikipedia/commons/thumb/8/8b/Paroxetine-2D-skeletal.svg/220px-Paroxetine-2D-skeletal.svg.png" decoding="async" width="220" height="204" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/8/8b/Paroxetine-2D-skeletal.svg/330px-Paroxetine-2D-skeletal.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/8/8b/Paroxetine-2D-skeletal.svg/440px-Paroxetine-2D-skeletal.svg.png 2x" data-file-width="512" data-file-height="475" /></a><figcaption>2D chemical structure of Paxil (<a href="/wiki/Paroxetine" title="Paroxetine">Paroxetine</a>), a <a href="/wiki/Selective_serotonin_reuptake_inhibitor" title="Selective serotonin reuptake inhibitor">selective serotonin reuptake inhibitor</a></figcaption></figure> <a href="/wiki/Selective_serotonin_reuptake_inhibitor" title="Selective serotonin reuptake inhibitor">Selective serotonin reuptake inhibitors</a> (SSRIs) are believed to increase the <a href="/wiki/Extracellular" class="mw-redirect" title="Extracellular">extracellular</a> level of the <a href="/wiki/Neurotransmitter" title="Neurotransmitter">neurotransmitter</a> serotonin by <a href="/wiki/Reuptake_inhibitor" title="Reuptake inhibitor">limiting</a> its <a href="/wiki/Reuptake" title="Reuptake">reabsorption</a> into the <a href="/wiki/Presynaptic_cell" class="mw-redirect" title="Presynaptic cell">presynaptic cell</a>, increasing the level of <a href="/wiki/Serotonin" title="Serotonin">serotonin</a> in the <a href="/wiki/Synaptic_cleft" class="mw-redirect" title="Synaptic cleft">synaptic cleft</a> available to bind to the <a href="/wiki/Postsynaptic_receptor" class="mw-redirect" title="Postsynaptic receptor">postsynaptic receptor</a>. They have varying degrees of selectivity for the other <a href="/wiki/Monoamine_transporter" title="Monoamine transporter">monoamine transporters</a>, with pure SSRIs having only weak affinity for the <a href="/wiki/Norepinephrine_transporter" title="Norepinephrine transporter">norepinephrine</a> and <a href="/wiki/Dopamine_transporter" title="Dopamine transporter">dopamine transporters</a>. SSRIs are the most widely prescribed antidepressants in many countries.<a href="#cite_note-PRESCORN2004-226">[226]</a> The efficacy of SSRIs in mild or moderate cases of depression has been disputed.<a href="#cite_note-JAMA2010-227">[227]</a><a href="#cite_note-Kramer-228">[228]</a><a href="#cite_note-Pies-229">[229]</a><a href="#cite_note-230">[230]</a> <div class="mw-heading mw-heading3"><h3 id="Serotonin–norepinephrine_reuptake_inhibitors">Serotonin–norepinephrine reuptake inhibitors</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=31" title="Edit section: Serotonin–norepinephrine reuptake inhibitors">edit</a>]</div> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:Venlafaxine-3D-balls.png" class="mw-file-description"><img alt="chemical structure of the SNRI drug venlafaxine" src="//upload.wikimedia.org/wikipedia/commons/thumb/2/28/Venlafaxine-3D-balls.png/220px-Venlafaxine-3D-balls.png" decoding="async" width="220" height="208" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/2/28/Venlafaxine-3D-balls.png/330px-Venlafaxine-3D-balls.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/2/28/Venlafaxine-3D-balls.png/440px-Venlafaxine-3D-balls.png 2x" data-file-width="1100" data-file-height="1041" /></a><figcaption>The chemical structure of <a href="/wiki/Venlafaxine" title="Venlafaxine">venlafaxine</a> (Effexor), an <a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitor" title="Serotonin–norepinephrine reuptake inhibitor">SNRI</a></figcaption></figure> <a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitor" title="Serotonin–norepinephrine reuptake inhibitor">Serotonin–norepinephrine reuptake inhibitors</a> (SNRIs) are potent inhibitors of the <a href="/wiki/Reuptake" title="Reuptake">reuptake</a> of <a href="/wiki/Serotonin" title="Serotonin">serotonin</a> and <a href="/wiki/Norepinephrine" title="Norepinephrine">norepinephrine</a>. These <a href="/wiki/Neurotransmitter" title="Neurotransmitter">neurotransmitters</a> are known to play an important role in mood. SNRIs can be contrasted with the more widely used <a href="/wiki/Selective_serotonin_reuptake_inhibitor" title="Selective serotonin reuptake inhibitor">selective serotonin reuptake inhibitors</a> (SSRIs), which act mostly upon serotonin alone. The human <a href="/wiki/Serotonin_transporter" title="Serotonin transporter">serotonin transporter</a> (SERT) and <a href="/wiki/Norepinephrine_transporter" title="Norepinephrine transporter">norepinephrine transporter</a> (NET) are <a href="/wiki/Membrane_protein" title="Membrane protein">membrane proteins</a> that are responsible for the reuptake of serotonin and norepinephrine. Balanced dual inhibition of <a href="/wiki/Monoamine" class="mw-redirect" title="Monoamine">monoamine</a> reuptake may offer advantages over other antidepressants drugs by treating a wider range of symptoms.<a href="#cite_note-pmid19740668-231">[231]</a> SNRIs are sometimes also used to treat <a href="/wiki/Anxiety_disorder" title="Anxiety disorder">anxiety disorders</a>, <a href="/wiki/Obsessive%E2%80%93compulsive_disorder" title="Obsessive–compulsive disorder">obsessive–compulsive disorder</a> (OCD), <a href="/wiki/Attention_deficit_hyperactivity_disorder" title="Attention deficit hyperactivity disorder">attention deficit hyperactivity disorder</a> (ADHD), chronic <a href="/wiki/Neuropathic_pain" title="Neuropathic pain">neuropathic pain</a>, and <a href="/wiki/Fibromyalgia_syndrome" class="mw-redirect" title="Fibromyalgia syndrome">fibromyalgia syndrome</a> (FMS), and for the relief of <a href="/wiki/Menopause" title="Menopause">menopausal</a> symptoms. <div class="mw-heading mw-heading3"><h3 id="Serotonin_modulators_and_stimulators">Serotonin modulators and stimulators</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=32" title="Edit section: Serotonin modulators and stimulators">edit</a>]</div> <a href="/wiki/Serotonin_modulator_and_stimulator" title="Serotonin modulator and stimulator">Serotonin modulator and stimulators</a> (SMSs), sometimes referred to more simply as "<a href="/wiki/Serotonin" title="Serotonin">serotonin</a> modulators", are a type of <a href="/wiki/Drug" title="Drug">drug</a> with a multimodal action specific to the serotonin <a href="/wiki/Neurotransmitter" title="Neurotransmitter">neurotransmitter</a> system. To be precise, SMSs simultaneously modulate one or more <a href="/wiki/Serotonin_receptor" class="mw-redirect" title="Serotonin receptor">serotonin receptors</a> and inhibit the <a href="/wiki/Reuptake" title="Reuptake">reuptake</a> of serotonin. The term was coined in reference to the <a href="/wiki/Mechanism_of_action" title="Mechanism of action">mechanism of action</a> of the serotonergic antidepressant <a href="/wiki/Vortioxetine" title="Vortioxetine">vortioxetine</a>, which acts as a <a href="/wiki/Serotonin_reuptake_inhibitor" title="Serotonin reuptake inhibitor">serotonin reuptake inhibitor</a> (SRI), a <a href="/wiki/Partial_agonist" title="Partial agonist">partial agonist</a> of the <a href="/wiki/5-HT1A_receptor" title="5-HT1A receptor">5-HT1A receptor</a>, and <a href="/wiki/Receptor_antagonist" title="Receptor antagonist">antagonist</a> of the <a href="/wiki/5-HT3_receptor" title="5-HT3 receptor">5-HT3</a> and <a href="/wiki/5-HT7_receptor" title="5-HT7 receptor">5-HT7 receptors</a>.<a href="#cite_note-pmid24391391-232">[232]</a><a href="#cite_note-AmerPharmAssoc2013-233">[233]</a><a href="#cite_note-LATimes2013-234">[234]</a> However, it can also technically be applied to <a href="/wiki/Vilazodone" title="Vilazodone">vilazodone</a>, which is an antidepressant as well and acts as an SRI and 5-HT1A receptor partial agonist.<a href="#cite_note-pmid15740724-235">[235]</a> An alternative term is serotonin partial agonist/reuptake inhibitor (SPARI), which can be applied only to vilazodone.<a href="#cite_note-236">[236]</a> <div class="mw-heading mw-heading3"><h3 id="Serotonin_antagonists_and_reuptake_inhibitors">Serotonin antagonists and reuptake inhibitors</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=33" title="Edit section: Serotonin antagonists and reuptake inhibitors">edit</a>]</div> <a href="/wiki/Serotonin_antagonist_and_reuptake_inhibitors" class="mw-redirect" title="Serotonin antagonist and reuptake inhibitors">Serotonin antagonist and reuptake inhibitors</a> (SARIs) while mainly used as antidepressants are also <a href="/wiki/Anxiolytic" title="Anxiolytic">anxiolytics</a> and <a href="/wiki/Hypnotic" title="Hypnotic">hypnotics</a>. They act by <a href="/wiki/Receptor_antagonist" title="Receptor antagonist">antagonizing</a> <a href="/wiki/Serotonin_receptor" class="mw-redirect" title="Serotonin receptor">serotonin receptors</a> such as <a href="/wiki/5-HT2A_receptor" title="5-HT2A receptor">5-HT2A</a> and <a href="/wiki/Reuptake_inhibitor" title="Reuptake inhibitor">inhibiting</a> the <a href="/wiki/Reuptake" title="Reuptake">reuptake</a> of <a href="/wiki/Serotonin" title="Serotonin">serotonin</a>, <a href="/wiki/Norepinephrine" title="Norepinephrine">norepinephrine</a>, and/or <a href="/wiki/Dopamine" title="Dopamine">dopamine</a>. Additionally, most also act as <a href="/wiki/Alpha-1_adrenergic_receptor" title="Alpha-1 adrenergic receptor">α1-adrenergic receptor</a> antagonists. The majority of the currently marketed SARIs belong to the <a href="/wiki/Phenylpiperazine" title="Phenylpiperazine">phenylpiperazine</a> class of compounds. They include <a href="/wiki/Trazodone" title="Trazodone">trazodone</a> and <a href="/wiki/Nefazodone" title="Nefazodone">nefazodone</a>. <div class="mw-heading mw-heading3"><h3 id="Tricyclic_antidepressants">Tricyclic antidepressants</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=34" title="Edit section: Tricyclic antidepressants">edit</a>]</div> The majority of the <a href="/wiki/Tricyclic_antidepressant" title="Tricyclic antidepressant">tricyclic antidepressants</a> (TCAs) act primarily as <a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitor" title="Serotonin–norepinephrine reuptake inhibitor">serotonin–norepinephrine reuptake inhibitors</a> (SNRIs) by blocking the <a href="/wiki/Serotonin_transporter" title="Serotonin transporter">serotonin transporter</a> (SERT) and the <a href="/wiki/Norepinephrine_transporter" title="Norepinephrine transporter">norepinephrine transporter</a> (NET), respectively, which results in an elevation of the <a href="/wiki/Synapse" title="Synapse">synaptic</a> concentrations of these <a href="/wiki/Neurotransmitter" title="Neurotransmitter">neurotransmitters</a>, and therefore an enhancement of <a href="/wiki/Neurotransmission" title="Neurotransmission">neurotransmission</a>.<a href="#cite_note-pmid9537821-237">[237]</a><a href="#cite_note-pmid17471183-238">[238]</a> Notably, with the sole exception of <a href="/wiki/Amineptine" title="Amineptine">amineptine</a>, the TCAs have weak <a href="/wiki/Affinity_(pharmacology)" class="mw-redirect" title="Affinity (pharmacology)">affinity</a> for the <a href="/wiki/Dopamine_transporter" title="Dopamine transporter">dopamine transporter</a> (DAT), and therefore have low efficacy as <a href="/wiki/Dopamine_reuptake_inhibitor" title="Dopamine reuptake inhibitor">dopamine reuptake inhibitors</a> (DRIs).<a href="#cite_note-pmid9537821-237">[237]</a> Although TCAs are sometimes <a href="/wiki/Medical_prescription" title="Medical prescription">prescribed</a> for depressive disorders, they have been largely replaced in clinical use in most parts of the world by newer antidepressants such as <a href="/wiki/Selective_serotonin_reuptake_inhibitor" title="Selective serotonin reuptake inhibitor">selective serotonin reuptake inhibitors</a> (SSRIs), <a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitor" title="Serotonin–norepinephrine reuptake inhibitor">serotonin–norepinephrine reuptake inhibitors</a> (SNRIs), and <a href="/wiki/Norepinephrine_reuptake_inhibitor" title="Norepinephrine reuptake inhibitor">norepinephrine reuptake inhibitors</a> (NRIs). Adverse effects have been found to be of a similar level between TCAs and SSRIs.<a href="#cite_note-239">[239]</a> <div class="mw-heading mw-heading3"><h3 id="Tetracyclic_antidepressants">Tetracyclic antidepressants</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=35" title="Edit section: Tetracyclic antidepressants">edit</a>]</div> <a href="/wiki/Tetracyclic_antidepressants" class="mw-redirect" title="Tetracyclic antidepressants">Tetracyclic antidepressants</a> (TeCAs) are a class of antidepressants that were first introduced in the 1970s. They are named after their <a href="/wiki/Chemical_structure" title="Chemical structure">chemical structure</a>, which contains four <a href="/wiki/Cyclic_compound" title="Cyclic compound">rings of atoms</a>, and are closely related to <a href="/wiki/Tricyclic_antidepressant" title="Tricyclic antidepressant">tricyclic antidepressants</a> (TCAs), which contain three rings of atoms. <div class="mw-heading mw-heading3"><h3 id="Monoamine_oxidase_inhibitors">Monoamine oxidase inhibitors</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=36" title="Edit section: Monoamine oxidase inhibitors">edit</a>]</div> <a href="/wiki/Monoamine_oxidase_inhibitor" title="Monoamine oxidase inhibitor">Monoamine oxidase inhibitors</a> (MAOIs) are chemicals that inhibit the activity of the <a href="/wiki/Monoamine_oxidase" title="Monoamine oxidase">monoamine oxidase enzyme family</a>. They have a long history of use as medications prescribed for the treatment of <a href="/wiki/Clinical_depression" class="mw-redirect" title="Clinical depression">depression</a>. They are particularly effective in treating <a href="/wiki/Atypical_depression" title="Atypical depression">atypical depression</a>.<a href="#cite_note-240">[240]</a> They are also used in the treatment of <a href="/wiki/Parkinson%27s_disease" title="Parkinson's disease">Parkinson's disease</a> and several other disorders. Because of potentially lethal dietary and drug interactions, MAOIs have historically been reserved as a last line of treatment, used only when other classes of antidepressant drugs (for example <a href="/wiki/Selective_serotonin_reuptake_inhibitor" title="Selective serotonin reuptake inhibitor">selective serotonin reuptake inhibitors</a> and <a href="/wiki/Tricyclic_antidepressant" title="Tricyclic antidepressant">tricyclic antidepressants</a>) have failed.<a href="#cite_note-241">[241]</a> MAOIs have been found to be effective in the treatment of <a href="/wiki/Panic_disorder" title="Panic disorder">panic disorder</a> with <a href="/wiki/Agoraphobia" title="Agoraphobia">agoraphobia</a>,<a href="#cite_note-242">[242]</a> <a href="/wiki/Social_phobia" class="mw-redirect" title="Social phobia">social phobia</a>,<a href="#cite_note-243">[243]</a><a href="#cite_note-244">[244]</a><a href="#cite_note-245">[245]</a> atypical depression<a href="#cite_note-246">[246]</a><a href="#cite_note-247">[247]</a> or mixed anxiety and depression, <a href="/wiki/Bulimia" class="mw-redirect" title="Bulimia">bulimia</a>,<a href="#cite_note-248">[248]</a><a href="#cite_note-249">[249]</a><a href="#cite_note-250">[250]</a><a href="#cite_note-251">[251]</a> and <a href="/wiki/Post-traumatic_stress_disorder" title="Post-traumatic stress disorder">post-traumatic stress disorder</a>,<a href="#cite_note-252">[252]</a> as well as <a href="/wiki/Borderline_personality_disorder" title="Borderline personality disorder">borderline personality disorder</a>.<a href="#cite_note-253">[253]</a> MAOIs appear to be particularly effective in the management of <a href="/wiki/Bipolar_disorder" title="Bipolar disorder">bipolar depression</a> according to a retrospective-analysis.<a href="#cite_note-254">[254]</a> There are reports of MAOI efficacy in <a href="/wiki/Obsessive%E2%80%93compulsive_disorder" title="Obsessive–compulsive disorder">obsessive–compulsive disorder</a> (OCD), <a href="/wiki/Trichotillomania" title="Trichotillomania">trichotillomania</a>, <a href="/wiki/Dysmorphophobia" class="mw-redirect" title="Dysmorphophobia">dysmorphophobia</a>, and <a href="/wiki/Avoidant_personality_disorder" title="Avoidant personality disorder">avoidant personality disorder</a>, but these reports are from uncontrolled case reports.<a href="#cite_note-pmid2248064-255">[255]</a> MAOIs can also be used in the treatment of Parkinson's disease by targeting MAO-B in particular (therefore affecting <a href="/wiki/Dopaminergic_neuron" class="mw-redirect" title="Dopaminergic neuron">dopaminergic neurons</a>), as well as providing an alternative for <a href="/wiki/Migraine" title="Migraine">migraine</a> <a href="/wiki/Prophylaxis" class="mw-redirect" title="Prophylaxis">prophylaxis</a>. Inhibition of both MAO-A and MAO-B is used in the treatment of <a href="/wiki/Clinical_depression" class="mw-redirect" title="Clinical depression">clinical depression</a> and <a href="/wiki/Anxiety_disorder" title="Anxiety disorder">anxiety disorders</a>. <div class="mw-heading mw-heading3"><h3 id="NMDA_receptor_antagonists">NMDA receptor antagonists</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=37" title="Edit section: NMDA receptor antagonists">edit</a>]</div> <a href="/wiki/NMDA_receptor_antagonist" title="NMDA receptor antagonist">NMDA receptor antagonists</a> like <a href="/wiki/Ketamine" title="Ketamine">ketamine</a> and <a href="/wiki/Esketamine" title="Esketamine">esketamine</a> are <a href="/wiki/Rapid-acting_antidepressant" class="mw-redirect" title="Rapid-acting antidepressant">rapid-acting antidepressants</a> and seem to work via <a href="/wiki/Receptor_antagonist" title="Receptor antagonist">blockade</a> of the <a href="/wiki/Ionotropic_glutamate_receptor" title="Ionotropic glutamate receptor">ionotropic glutamate</a> <a href="/wiki/NMDA_receptor" title="NMDA receptor">NMDA receptor</a>.<a href="#cite_note-SpravatoLabel-256">[256]</a> Other NMDA antagonists may also play a role in treating depression. The combination medication <a href="/wiki/Dextromethorphan/bupropion" title="Dextromethorphan/bupropion">dextromethorphan/bupropion</a> (Auvelity), which contains the NMDA receptor antagonist <a href="/wiki/Dextromethorphan" title="Dextromethorphan">dextromethorphan</a>, was approved in the United States in 2022 for treating major depressive disorder.<a href="#cite_note-pmid36301443-257">[257]</a><a href="#cite_note-pmid36943010-258">[258]</a> <div class="mw-heading mw-heading3"><h3 id="Others">Others</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=38" title="Edit section: Others">edit</a>]</div> See the <a href="/wiki/List_of_antidepressants" title="List of antidepressants">list of antidepressants</a> and <a href="/wiki/Management_of_depression" title="Management of depression">management of depression</a> for other drugs that are not specifically characterized. <div class="mw-heading mw-heading2"><h2 id="Adjuncts">Adjuncts</h2>[<a href="/w/index.php?title=Antidepressant&action=edit&section=39" title="Edit section: Adjuncts">edit</a>]</div> Adjunct medications are an umbrella category of substances that increase the potency or "enhance" antidepressants.<a href="#cite_note-259">[259]</a> They work by affecting variables very close to the antidepressant, sometimes affecting a completely different <a href="/wiki/Mechanism_of_action" title="Mechanism of action">mechanism of action</a>. This may be attempted when depression treatments have not been successful in the past. Common types of adjunct medication techniques generally fall into the following categories: <ul><li>Two or more antidepressants taken together, from either the same or different classes (affecting the same area of the brain, often at a much higher level).</li> <li>An <a href="/wiki/Antipsychotic" title="Antipsychotic">antipsychotic</a> combined with an antidepressant, particularly <a href="/wiki/Atypical_antipsychotic" title="Atypical antipsychotic">atypical antipsychotics</a> such as <a href="/wiki/Aripiprazole" title="Aripiprazole">aripiprazole</a> (Abilify), <a href="/wiki/Quetiapine" title="Quetiapine">quetiapine</a> (Seroquel), <a href="/wiki/Olanzapine" title="Olanzapine">olanzapine</a> (Zyprexa), and <a href="/wiki/Risperidone" title="Risperidone">risperidone</a> (Risperdal).<a href="#cite_note-Maudsley-260">[260]</a></li></ul> It is unknown if undergoing <a href="/wiki/Psychological_therapy" class="mw-redirect" title="Psychological therapy">psychological therapy</a> at the same time as taking anti-depressants enhances the anti-depressive effect of the medication.<a href="#cite_note-261">[261]</a> <div class="mw-heading mw-heading3"><h3 id="Less_common_adjuncts">Less common adjuncts</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=40" title="Edit section: Less common adjuncts">edit</a>]</div> <a href="/wiki/Lithium_(medication)" title="Lithium (medication)">Lithium</a> has been used to augment antidepressant therapy in those who have failed to respond to antidepressants alone.<a href="#cite_note-pmid10505584-262">[262]</a> Furthermore, Lithium dramatically decreases the suicide risk in recurrent depression.<a href="#cite_note-pmid17388706-263">[263]</a> There is some evidence for the addition of a thyroid hormone, <a href="/wiki/Triiodothyronine" title="Triiodothyronine">triiodothyronine</a>, in patients with normal thyroid function.<a href="#cite_note-pmid16946176-264">[264]</a> Psychopharmacologists have also tried adding a <a href="/wiki/Psychostimulant" class="mw-redirect" title="Psychostimulant">stimulant</a>, in particular, <a href="/wiki/D-amphetamine" class="mw-redirect" title="D-amphetamine">D-amphetamine</a>.<a href="#cite_note-265">[265]</a> However, the use of stimulants in cases of treatment-resistant depression is relatively controversial.<a href="#cite_note-pmid1411740-266">[266]</a><a href="#cite_note-pmid17338594-267">[267]</a> A review article published in 2007 found psychostimulants may be effective in treatment-resistant depression with concomitant antidepressant therapy, but a more certain conclusion could not be drawn due to substantial deficiencies in the studies available for consideration, and the somewhat contradictory nature of their results.<a href="#cite_note-pmid17338594-267">[267]</a> <div class="mw-heading mw-heading2"><h2 id="History">History</h2>[<a href="/w/index.php?title=Antidepressant&action=edit&section=41" title="Edit section: History">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">See also: <a href="/wiki/Discovery_and_development_of_dual_serotonin_and_norepinephrine_reuptake_inhibitors" class="mw-redirect" title="Discovery and development of dual serotonin and norepinephrine reuptake inhibitors">Discovery and development of dual serotonin and norepinephrine reuptake inhibitors</a></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Saint_John%27s_wort_flowers.jpg" class="mw-file-description"><img alt="refer to caption" src="//upload.wikimedia.org/wikipedia/commons/thumb/4/47/Saint_John%27s_wort_flowers.jpg/220px-Saint_John%27s_wort_flowers.jpg" decoding="async" width="220" height="147" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/4/47/Saint_John%27s_wort_flowers.jpg/330px-Saint_John%27s_wort_flowers.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/4/47/Saint_John%27s_wort_flowers.jpg/440px-Saint_John%27s_wort_flowers.jpg 2x" data-file-width="1600" data-file-height="1067" /></a><figcaption><a href="/wiki/Hypericum_perforatum" title="Hypericum perforatum">St John's wort</a></figcaption></figure> The idea of an antidepressant, if <a href="/wiki/Melancholia" title="Melancholia">melancholy</a> is thought synonymous with depression, existed at least as early as the 1599 pamphlet A pil to purge melancholie or, A preprative to a pvrgation: or, Topping, copping, and capping: take either or whether: or, Mash them, and squash them, and dash them, and diddle come derrie come daw them, all together... <a href="/wiki/Thomas_d%27Urfey" title="Thomas d'Urfey">Thomas d'Urfey</a>'s Wit and Mirth: Or <a href="/wiki/Pills_to_Purge_Melancholy" class="mw-redirect" title="Pills to Purge Melancholy">Pills to Purge Melancholy</a>, the title of a large collection of songs, was published between 1698 and 1720. Before the 1950s, <a href="/wiki/Opioid" title="Opioid">opioids</a> and <a href="/wiki/Amphetamine-type_stimulant" class="mw-redirect" title="Amphetamine-type stimulant">amphetamines</a> were commonly used as antidepressants.<a href="#cite_note-Weber_1988_255–66-268">[268]</a><a href="#cite_note-Amph_Uses_Dex-269">[269]</a><a href="#cite_note-Rasmussen2006-196">[196]</a> <a href="/wiki/Amphetamine" title="Amphetamine">Amphetamine</a> has been described as the first antidepressant.<a href="#cite_note-Rasmussen2006-196">[196]</a> Use of opioids and amphetamines for depression was later restricted due to their addictive nature and side effects.<a href="#cite_note-Weber_1988_255–66-268">[268]</a><a href="#cite_note-Rasmussen2006-196">[196]</a> Extracts from the herb <a href="/wiki/Hypericum_perforatum" title="Hypericum perforatum">St John's wort</a> have been used as a "nerve tonic" to alleviate depression.<a href="#cite_note-270">[270]</a> <a href="/wiki/Hypericum_perforatum" title="Hypericum perforatum">St John's wort</a> fell out of favor in most countries through the 19th and 20th centuries, except in <a href="/wiki/Germany" title="Germany">Germany</a>, where <a href="/wiki/Hypericum" title="Hypericum">Hypericum</a> extracts were eventually licensed, packaged, and prescribed. Small-scale efficacy trials were carried out in the 1970s and 1980s, and attention grew in the 1990s following a <a href="/wiki/Meta-analysis" title="Meta-analysis">meta-analysis</a>.<a href="#cite_note-271">[271]</a> It remains an <a href="/wiki/Over-the-counter_drug" title="Over-the-counter drug">over-the-counter</a> (OTC) supplement in most countries. Lead contamination associated with its usage has been seen as concerning, as lead levels in women in the United States taking St. John's wort are elevated by about 20% on average.<a href="#cite_note-LeadInHerbs-272">[272]</a> Research continues to investigate its active component <a href="/wiki/Hyperforin" title="Hyperforin">hyperforin</a>, and to further understand its mode of action.<a href="#cite_note-273">[273]</a><a href="#cite_note-274">[274]</a> <div class="mw-heading mw-heading3"><h3 id="Isoniazid,_iproniazid,_and_imipramine">Isoniazid, iproniazid, and imipramine</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=42" title="Edit section: Isoniazid, iproniazid, and imipramine">edit</a>]</div> In 1951, <a href="/wiki/Irving_Selikoff" title="Irving Selikoff">Irving Selikoff</a> and Edward H. Robitzek, working out of <a href="/wiki/Sea_View_Hospital" class="mw-redirect" title="Sea View Hospital">Sea View Hospital</a> on <a href="/wiki/Staten_Island" title="Staten Island">Staten Island</a>, began clinical trials on two new <a href="/wiki/Tuberculosis" title="Tuberculosis">anti-tuberculosis</a> agents developed by Hoffman-LaRoche, <a href="/wiki/Isoniazid" title="Isoniazid">isoniazid</a>, and <a href="/wiki/Iproniazid" title="Iproniazid">iproniazid</a>. Only patients with a poor <a href="/wiki/Prognosis" title="Prognosis">prognosis</a> were initially treated. Nevertheless, their condition improved dramatically. Selikoff and Robitzek noted "a subtle general stimulation ... the patients exhibited renewed vigor and indeed this occasionally served to introduce disciplinary problems."<a href="#cite_note-pmid14906149-275">[275]</a> The promise of a cure for tuberculosis in the Sea View Hospital trials was excitedly discussed in the mainstream press. In 1952, learning of the stimulating side effects of isoniazid, the Cincinnati psychiatrist Max Lurie tried it on his patients. In the following year, he and Harry Salzer reported that isoniazid improved depression in two-thirds of their patients, so they then coined the term antidepressant to refer to its action.<a href="#cite_note-isbn0-88048-397-0-276">[276]</a> A similar incident took place in Paris, where <a href="/wiki/Jean_Delay" title="Jean Delay">Jean Delay</a>, head of psychiatry at Sainte-Anne Hospital, heard of this effect from his <a href="/wiki/Pulmonology" title="Pulmonology">pulmonology</a> colleagues at Cochin Hospital. In 1952 (before Lurie and Salzer), Delay, with the resident Jean-Francois Buisson, reported the positive effect of isoniazid on depressed patients.<a href="#cite_note-Healy96-277">[277]</a> The mode of antidepressant action of isoniazid is still unclear. It is speculated that its effect is due to the inhibition of <a href="/wiki/Diamine_oxidase" title="Diamine oxidase">diamine oxidase</a>, coupled with a weak inhibition of <a href="/wiki/Monoamine_oxidase_A" title="Monoamine oxidase A">monoamine oxidase A</a>.<a href="#cite_note-isbn1-86036-010-6-278">[278]</a> Selikoff and Robitzek also experimented with another anti-tuberculosis drug, <a href="/wiki/Iproniazid" title="Iproniazid">iproniazid</a>; it showed a greater psychostimulant effect, but more pronounced toxicity.<a href="#cite_note-pmid12998444-279">[279]</a> Later, Jackson Smith, Gordon Kamman, George E. Crane, and <a href="/wiki/Frank_Ayd" title="Frank Ayd">Frank Ayd</a>, described the psychiatric applications of iproniazid. <a href="/w/index.php?title=Ernst_Zeller&action=edit&redlink=1" class="new" title="Ernst Zeller (page does not exist)">Ernst Zeller</a> found iproniazid to be a potent <a href="/wiki/Monoamine_oxidase_inhibitor" title="Monoamine oxidase inhibitor">monoamine oxidase inhibitor</a>.<a href="#cite_note-pmid18004120-280">[280]</a> Nevertheless, iproniazid remained relatively obscure until <a href="/wiki/Nathan_S._Kline" title="Nathan S. Kline">Nathan S. Kline</a>, the influential head of research at <a href="/wiki/Rockland_State_Hospital" class="mw-redirect" title="Rockland State Hospital">Rockland State Hospital</a>, began to popularize it in the medical and popular press as a "psychic energizer".<a href="#cite_note-pmid18004120-280">[280]</a><a href="#cite_note-281">[281]</a> Roche put a significant marketing effort behind iproniazid.<a href="#cite_note-pmid18004120-280">[280]</a> Its sales grew until it was recalled in 1961, due to reports of lethal <a href="/wiki/Hepatotoxicity" title="Hepatotoxicity">hepatotoxicity</a>.<a href="#cite_note-pmid18004120-280">[280]</a> The antidepressant effect of a <a href="/wiki/Tricyclic_antidepressant" title="Tricyclic antidepressant">tricyclic antidepressant</a>, a three-ringed compound, was first discovered in 1957 by <a href="/wiki/Roland_Kuhn" title="Roland Kuhn">Roland Kuhn</a> in a Swiss <a href="/wiki/Psychiatric_hospital" title="Psychiatric hospital">psychiatric hospital</a>. <a href="/wiki/Antihistamine" title="Antihistamine">Antihistamine</a> derivatives were used to treat surgical shock and later as <a href="/wiki/Neuroleptics" class="mw-redirect" title="Neuroleptics">neuroleptics</a>. Although in 1955, <a href="/wiki/Reserpine" title="Reserpine">reserpine</a> was shown to be more effective than a placebo in alleviating anxious depression, neuroleptics were being developed as <a href="/wiki/Sedative" title="Sedative">sedatives</a> and <a href="/wiki/Antipsychotic" title="Antipsychotic">antipsychotics</a>.[<a href="/wiki/Wikipedia:Identifying_reliable_sources_(medicine)" title="Wikipedia:Identifying reliable sources (medicine)">medical citation needed</a>] Attempting to improve the effectiveness of <a href="/wiki/Chlorpromazine" title="Chlorpromazine">chlorpromazine</a>, Kuhn — in conjunction with the <a href="/wiki/Geigy" class="mw-redirect" title="Geigy">Geigy</a> Pharmaceutical Company — discovered the compound "G 22355", later renamed <a href="/wiki/Imipramine" title="Imipramine">imipramine</a>. Imipramine had a beneficial effect on patients with depression who showed mental and <a href="/wiki/Motor_retardation" class="mw-redirect" title="Motor retardation">motor retardation</a>. Kuhn described his new compound as a "thymoleptic" "taking hold of the emotions," in contrast with neuroleptics, "taking hold of the nerves" in 1955–56. These gradually became established, resulting in the patent and manufacture in the US in 1951 by Häfliger and SchinderA.<a href="#cite_note-282">[282]</a> Antidepressants became <a href="/wiki/Prescription_drug" title="Prescription drug">prescription drugs</a> in the 1950s. It was estimated that no more than fifty to one hundred individuals per million had the kind of depression that these new drugs would treat, and pharmaceutical companies were not enthusiastic about marketing for this small market. Sales through the 1960s remained poor compared to the sales of tranquilizers,<a href="#cite_note-283">[283]</a>[<a href="/wiki/Wikipedia:Identifying_reliable_sources_(medicine)" title="Wikipedia:Identifying reliable sources (medicine)">unreliable medical source?</a>] which were being marketed for different uses.<a href="#cite_note-3faces-284">[284]</a> Imipramine remained in common use and numerous successors were introduced. The use of monoamine oxidase inhibitors (MAOI) increased after the development and introduction of "reversible" forms affecting only the MAO-A subtype of inhibitors, making this drug safer to use.<a href="#cite_note-3faces-284">[284]</a><a href="#cite_note-285">[285]</a> By the 1960s, it was thought that the mode of action of tricyclics was to inhibit norepinephrine reuptake. However, norepinephrine reuptake became associated with stimulating effects. Later tricyclics were thought to affect <a href="/wiki/Serotonin" title="Serotonin">serotonin</a> as proposed in 1969 by Carlsson and Lindqvist as well as Lapin and Oxenkrug.[<a href="/wiki/Wikipedia:Identifying_reliable_sources_(medicine)" title="Wikipedia:Identifying reliable sources (medicine)">medical citation needed</a>] <div class="mw-heading mw-heading3"><h3 id="Second-generation_antidepressants">Second-generation antidepressants</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=43" title="Edit section: Second-generation antidepressants">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Second-generation_antidepressants" class="mw-redirect" title="Second-generation antidepressants">Second-generation antidepressants</a></div> Researchers began a process of <a href="/wiki/Rational_drug_design" class="mw-redirect" title="Rational drug design">rational drug design</a> to isolate antihistamine-derived compounds that would selectively target these systems. The first such compound to be patented was <a href="/wiki/Zimelidine" title="Zimelidine">zimelidine</a> in 1971, while the first released clinically was <a href="/wiki/Indalpine" title="Indalpine">indalpine</a>. <a href="/wiki/Fluoxetine" title="Fluoxetine">Fluoxetine</a> was approved for commercial use by the US <a href="/wiki/Food_and_Drug_Administration" title="Food and Drug Administration">Food and Drug Administration</a> (FDA) in 1988, becoming the first <a href="/wiki/Blockbuster_drug" class="mw-redirect" title="Blockbuster drug">blockbuster</a> SSRI. Fluoxetine was developed at <a href="/wiki/Eli_Lilly_and_Company" title="Eli Lilly and Company">Eli Lilly and Company</a> in the early 1970s by <a href="/wiki/Bryan_Molloy" title="Bryan Molloy">Bryan Molloy</a>, <a href="/wiki/Klaus_Schmiegel" title="Klaus Schmiegel">Klaus Schmiegel</a>, <a href="/wiki/David_T._Wong" title="David T. Wong">David T. Wong</a>, and others.<a href="#cite_note-286">[286]</a><a href="#cite_note-287">[287]</a> SSRIs became known as "novel antidepressants" along with other newer drugs such as SNRIs and <a href="/wiki/Norepinephrine_Reuptake_Inhibitor" class="mw-redirect" title="Norepinephrine Reuptake Inhibitor">NRIs</a> with various selective effects.<a href="#cite_note-288">[288]</a> <div class="mw-heading mw-heading3"><h3 id="Rapid-acting_antidepressants">Rapid-acting antidepressants</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=44" title="Edit section: Rapid-acting antidepressants">edit</a>]</div> <a href="/wiki/Esketamine" title="Esketamine">Esketamine</a> (brand name Spravato), the first rapid-acting antidepressant to be approved for clinical treatment of depression, was introduced for this indication in March 2019 in the United States.<a href="#cite_note-SpravatoLabel-256">[256]</a> <div class="mw-heading mw-heading4"><h4 id="Research">Research</h4>[<a href="/w/index.php?title=Antidepressant&action=edit&section=45" title="Edit section: Research">edit</a>]</div> A 2016 <a href="/wiki/Randomized_controlled_trial" title="Randomized controlled trial">randomized controlled trial</a> evaluated the <a href="#Rapid-acting_antidepressants">rapid antidepressant</a> effects of the psychedelic <a href="/wiki/Ayahuasca" title="Ayahuasca">Ayahuasca</a> in treatment-resistant depression with a positive outcome.<a href="#cite_note-289">[289]</a><a href="#cite_note-290">[290]</a> In 2018, the FDA granted Breakthrough Therapy Designation for <a href="/wiki/Psilocybin" title="Psilocybin">psilocybin</a>-assisted therapy for treatment-resistant depression and in 2019, the FDA granted Breakthrough Therapy Designation for psilocybin therapy treating major depressive disorder.<a href="#cite_note-291">[291]</a> <div class="mw-heading mw-heading3"><h3 id="Publication_bias_and_aged_research">Publication bias and aged research</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=46" title="Edit section: Publication bias and aged research">edit</a>]</div> A 2018 systematic review published in <a href="/wiki/The_Lancet" title="The Lancet">The Lancet</a> comparing the efficacy of 21 different first and second generation antidepressants found that antidepressant drugs tended to perform better and cause less adverse events when they were novel or experimental treatments compared to when they were evaluated again years later.<a href="#cite_note-292">[292]</a> Unpublished data was also associated with smaller positive effect sizes. However, the review did not find evidence of bias associated with industry funded research. <div class="mw-heading mw-heading2"><h2 id="Society_and_culture">Society and culture</h2>[<a href="/w/index.php?title=Antidepressant&action=edit&section=47" title="Edit section: Society and culture">edit</a>]</div> <div class="mw-heading mw-heading3"><h3 id="Prescription_trends">Prescription trends</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=48" title="Edit section: Prescription trends">edit</a>]</div> <div class="mw-heading mw-heading4"><h4 id="United_Kingdom">United Kingdom</h4>[<a href="/w/index.php?title=Antidepressant&action=edit&section=49" title="Edit section: United Kingdom">edit</a>]</div> In the UK, figures reported in 2010 indicated that the number of antidepressants prescribed by the <a href="/wiki/National_Health_Service" title="National Health Service">National Health Service</a> (NHS) almost doubled over a decade.<a href="#cite_note-293">[293]</a> Further analysis published in 2014 showed that number of antidepressants dispensed annually in the community went up by 25 million in the 14 years between 1998 and 2012, rising from 15 million to 40 million. Nearly 50% of this rise occurred in the four years after the <a href="/wiki/Great_Recession" title="Great Recession">Great Recession</a>, during which time the annual increase in prescriptions rose from 6.7% to 8.5%.<a href="#cite_note-294">[294]</a> These sources also suggest that aside from the recession, other factors that may influence changes in prescribing rates may include: improvements in diagnosis, a reduction of the <a href="/wiki/Social_stigma" title="Social stigma">stigma</a> surrounding mental health, broader prescribing trends, GP characteristics, geographical location, and housing status. Another factor that may contribute to increasing consumption of antidepressants is the fact that these medications now are used for other conditions including <a href="/wiki/Social_anxiety" title="Social anxiety">social anxiety</a> and <a href="/wiki/Post-traumatic_stress_disorder" title="Post-traumatic stress disorder">post-traumatic stress disorder</a>. Between 2005 and 2017, the number of adolescents (12 to 17 years) in England who were prescribed antidepressants has doubled. On the other hand, antidepressant prescriptions for children aged 5–11 in England decreased between 1999 and 2017.<a href="#cite_note-295">[295]</a><a href="#cite_note-296">[296]</a> From April 2015, prescriptions increased for both age groups (for people aged 0 to 17) and peaked during the first COVID lockdown in March 2020.<a href="#cite_note-297">[297]</a> According to <a href="/wiki/National_Institute_for_Health_and_Care_Excellence" title="National Institute for Health and Care Excellence">National Institute for Health and Care Excellence</a> (NICE) guidelines, antidepressants for children and adolescents with depression and obsessive-compulsive disorder (OCD) should be prescribed together with therapy and after being assessed by a <a href="/wiki/Child_and_adolescent_psychiatry" title="Child and adolescent psychiatry">child and adolescent psychiatrist</a>. However, between 2006 and 2017, only 1 in 4 of 12–17 year-olds who were prescribed an SSRI by their GP had seen a specialist psychiatrist and 1 in 6 has seen a pediatrician. Half of these prescriptions were for depression and 16% for anxiety, the latter not being licensed for treatment with antidepressants.<a href="#cite_note-NIHR-2022-42">[42]</a><a href="#cite_note-298">[298]</a> Among the suggested possible reasons why GPs are not following the guidelines are the difficulties of accessing talking therapies, long waiting lists, and the urgency of treatment.<a href="#cite_note-NIHR-2022-42">[42]</a><a href="#cite_note-299">[299]</a> According to some researchers, strict adherence to treatment guidelines would limit access to effective medication for young people with mental health problems.<a href="#cite_note-300">[300]</a> <div class="mw-heading mw-heading4"><h4 id="United_States">United States</h4>[<a href="/w/index.php?title=Antidepressant&action=edit&section=50" title="Edit section: United States">edit</a>]</div> In the United States, antidepressants were the most commonly prescribed medication in 2013.<a href="#cite_note-AJantidepressantstatsUS-301">[301]</a> Of the estimated 16 million "long term" (over 24 months) users, roughly 70 percent are female.<a href="#cite_note-AJantidepressantstatsUS-301">[301]</a> As of 2017<a class="external text" href="https://en.wikipedia.org/w/index.php?title=Antidepressant&action=edit">[update]</a>, about 16.5% of white people in the United States took antidepressants compared with 5.6% of black people in the United States.<a href="#cite_note-APP2017-302">[302]</a> <figure class="mw-default-size skin-invert-image" typeof="mw:File/Thumb"><img alt="" resource="/wiki/File:Sertraline2DACS2.svg" src="//upload.wikimedia.org/wikipedia/commons/thumb/8/84/Sertraline2DACS2.svg/220px-Sertraline2DACS2.svg.png" decoding="async" width="220" height="175" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/8/84/Sertraline2DACS2.svg/330px-Sertraline2DACS2.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/8/84/Sertraline2DACS2.svg/440px-Sertraline2DACS2.svg.png 2x" data-file-width="709" data-file-height="564" /><figcaption>Structural formula of the SSRI <a href="/wiki/Sertraline" title="Sertraline">sertraline</a></figcaption></figure> United States: The most commonly prescribed antidepressants in the US retail market in 2010 were:<a href="#cite_note-303">[303]</a> <table class="wikitable sortable"> <tbody><tr> <th scope="col">Drug name </th> <th scope="col">Drug class </th> <th scope="col">Total prescriptions </th></tr> <tr> <td><a href="/wiki/Sertraline" title="Sertraline">Sertraline</a> </td> <td><a href="/wiki/SSRI" class="mw-redirect" title="SSRI">SSRI</a> </td> <td>33,409,838 </td></tr> <tr> <td><a href="/wiki/Citalopram" title="Citalopram">Citalopram</a> </td> <td><a href="/wiki/SSRI" class="mw-redirect" title="SSRI">SSRI</a> </td> <td>27,993,635 </td></tr> <tr> <td><a href="/wiki/Fluoxetine" title="Fluoxetine">Fluoxetine</a> </td> <td><a href="/wiki/SSRI" class="mw-redirect" title="SSRI">SSRI</a> </td> <td>24,473,994 </td></tr> <tr> <td><a href="/wiki/Escitalopram" title="Escitalopram">Escitalopram</a> </td> <td><a href="/wiki/SSRI" class="mw-redirect" title="SSRI">SSRI</a> </td> <td>23,000,456 </td></tr> <tr> <td><a href="/wiki/Trazodone" title="Trazodone">Trazodone</a> </td> <td><a href="/wiki/Serotonin_antagonist_and_reuptake_inhibitor" title="Serotonin antagonist and reuptake inhibitor">SARI</a> </td> <td>18,786,495 </td></tr> <tr> <td><a href="/wiki/Venlafaxine" title="Venlafaxine">Venlafaxine</a> (all formulations) </td> <td><a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitor" title="Serotonin–norepinephrine reuptake inhibitor">SNRI</a> </td> <td>16,110,606 </td></tr> <tr> <td><a href="/wiki/Bupropion" title="Bupropion">Bupropion</a> (all formulations) </td> <td><a href="/wiki/Norepinephrine%E2%80%93dopamine_reuptake_inhibitor" title="Norepinephrine–dopamine reuptake inhibitor">NDRI</a> </td> <td>15,792,653 </td></tr> <tr> <td><a href="/wiki/Duloxetine" title="Duloxetine">Duloxetine</a> </td> <td><a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitor" title="Serotonin–norepinephrine reuptake inhibitor">SNRI</a> </td> <td>14,591,949 </td></tr> <tr> <td><a href="/wiki/Paroxetine" title="Paroxetine">Paroxetine</a> </td> <td><a href="/wiki/SSRI" class="mw-redirect" title="SSRI">SSRI</a> </td> <td>12,979,366 </td></tr> <tr> <td><a href="/wiki/Amitriptyline" title="Amitriptyline">Amitriptyline</a> </td> <td><a href="/wiki/Tricyclic_antidepressant" title="Tricyclic antidepressant">TCA</a> </td> <td>12,611,254 </td></tr> <tr> <td><a href="/wiki/Venlafaxine" title="Venlafaxine">Venlafaxine</a> XR </td> <td><a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitor" title="Serotonin–norepinephrine reuptake inhibitor">SNRI</a> </td> <td>7,603,949 </td></tr> <tr> <td><a href="/wiki/Bupropion" title="Bupropion">Bupropion</a> XL </td> <td><a href="/wiki/Norepinephrine%E2%80%93dopamine_reuptake_inhibitor" title="Norepinephrine–dopamine reuptake inhibitor">NDRI</a> </td> <td>7,317,814 </td></tr> <tr> <td><a href="/wiki/Mirtazapine" title="Mirtazapine">Mirtazapine</a> </td> <td><a href="/wiki/Tetracyclic_antidepressant" title="Tetracyclic antidepressant">TeCA</a> </td> <td>6,308,288 </td></tr> <tr> <td><a href="/wiki/Venlafaxine" title="Venlafaxine">Venlafaxine</a> ER </td> <td><a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitor" title="Serotonin–norepinephrine reuptake inhibitor">SNRI</a> </td> <td>5,526,132 </td></tr> <tr> <td><a href="/wiki/Bupropion" title="Bupropion">Bupropion</a> SR </td> <td><a href="/wiki/Norepinephrine%E2%80%93dopamine_reuptake_inhibitor" title="Norepinephrine–dopamine reuptake inhibitor">NDRI</a> </td> <td>4,588,996 </td></tr> <tr> <td><a href="/wiki/Desvenlafaxine" title="Desvenlafaxine">Desvenlafaxine</a> </td> <td><a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitor" title="Serotonin–norepinephrine reuptake inhibitor">SNRI</a> </td> <td>3,412,354 </td></tr> <tr> <td><a href="/wiki/Nortriptyline" title="Nortriptyline">Nortriptyline</a> </td> <td><a href="/wiki/Tricyclic_antidepressant" title="Tricyclic antidepressant">TCA</a> </td> <td>3,210,476 </td></tr> <tr> <td><a href="/wiki/Bupropion" title="Bupropion">Bupropion</a> ER </td> <td><a href="/wiki/Norepinephrine%E2%80%93dopamine_reuptake_inhibitor" title="Norepinephrine–dopamine reuptake inhibitor">NDRI</a> </td> <td>3,132,327 </td></tr> <tr> <td><a href="/wiki/Venlafaxine" title="Venlafaxine">Venlafaxine</a> </td> <td><a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitor" title="Serotonin–norepinephrine reuptake inhibitor">SNRI</a> </td> <td>2,980,525 </td></tr> <tr> <td><a href="/wiki/Bupropion" title="Bupropion">Bupropion</a> </td> <td><a href="/wiki/Norepinephrine%E2%80%93dopamine_reuptake_inhibitor" title="Norepinephrine–dopamine reuptake inhibitor">NDRI</a> </td> <td>753,516 </td></tr></tbody></table> Netherlands: In the Netherlands, <a href="/wiki/Paroxetine" title="Paroxetine">paroxetine</a> is the most prescribed antidepressant, followed by <a href="/wiki/Amitriptyline" title="Amitriptyline">amitriptyline</a>, <a href="/wiki/Citalopram" title="Citalopram">citalopram</a> and <a href="/wiki/Venlafaxine" title="Venlafaxine">venlafaxine</a>.<a href="#cite_note-304">[304]</a> <div class="mw-heading mw-heading3"><h3 id="Adherence">Adherence</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=51" title="Edit section: Adherence">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Adherence_(medicine)" title="Adherence (medicine)">Adherence (medicine)</a></div> As of 2003<a class="external text" href="https://en.wikipedia.org/w/index.php?title=Antidepressant&action=edit">[update]</a>, worldwide, 30% to 60% of people did not follow their practitioner's instructions about taking their antidepressants,<a href="#cite_note-305">[305]</a> and as of 2013<a class="external text" href="https://en.wikipedia.org/w/index.php?title=Antidepressant&action=edit">[update]</a> in the US, it appeared that around 50% of people did not take their antidepressants as directed by their practitioner.<a href="#cite_note-Kaplan-2013-306">[306]</a> When people fail to take their antidepressants, there is a greater risk that the drug will not help, that symptoms get worse, that they miss work or are less productive at work, and that the person may be hospitalized.<a href="#cite_note-Ho2016-307">[307]</a> <div class="mw-heading mw-heading3"><h3 id="Social_science_perspective">Social science perspective</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=52" title="Edit section: Social science perspective">edit</a>]</div> Some academics[<a href="/wiki/Wikipedia:Manual_of_Style/Words_to_watch#Unsupported_attributions" title="Wikipedia:Manual of Style/Words to watch">who?</a>] have highlighted the need to examine the use of antidepressants and other medical treatments in cross-cultural terms, because various cultures prescribe and observe different manifestations, symptoms, meanings, and associations of depression and other medical conditions within their populations.<a href="#cite_note-Ecks_2005-308">[308]</a><a href="#cite_note-Lock_2010-309">[309]</a> These cross-cultural discrepancies, it has been argued, then have implications on the perceived efficacy and use of antidepressants and other strategies in the treatment of depression in these different cultures.<a href="#cite_note-Ecks_2005-308">[308]</a><a href="#cite_note-Lock_2010-309">[309]</a> In India, antidepressants are largely seen as tools to combat marginality, promising the individual the ability to reintegrate into society through their use—a view and association not observed in the West.<a href="#cite_note-Ecks_2005-308">[308]</a> <div class="mw-heading mw-heading3"><h3 id="Environmental_impacts">Environmental impacts</h3>[<a href="/w/index.php?title=Antidepressant&action=edit&section=53" title="Edit section: Environmental impacts">edit</a>]</div> Because most antidepressants function by inhibiting the reuptake of neurotransmitters serotonin, dopamine, and norepinephrine<a href="#cite_note-pmid17690258-310">[310]</a> these drugs can interfere with natural neurotransmitter levels in other organisms impacted by indirect exposure.<a href="#cite_note-311">[311]</a> Antidepressants fluoxetine and sertraline have been detected in aquatic organisms residing in effluent-dominated streams.<a href="#cite_note-pmid15720009-312">[312]</a> The presence of antidepressants in surface waters and aquatic organisms has caused concern because ecotoxicological effects on aquatic organisms due to fluoxetine exposure have been demonstrated.<a href="#cite_note-pmid16257063-313">[313]</a> Coral reef fish have been demonstrated to modulate aggressive behavior through serotonin.<a href="#cite_note-314">[314]</a> Artificially increasing serotonin levels in crustaceans can temporarily reverse social status and turn subordinates into aggressive and territorial dominant males.<a href="#cite_note-pmid9159179-315">[315]</a> Exposure to Fluoxetine has been demonstrated to increase serotonergic activity in fish, subsequently reducing aggressive behavior.<a href="#cite_note-pmid12954414-316">[316]</a> Perinatal exposure to Fluoxetine at relevant environmental concentrations has been shown to lead to significant modifications of memory processing in 1-month-old cuttlefish.<a href="#cite_note-pmid23474317-317">[317]</a> This impairment may disadvantage cuttlefish and decrease their survival. Somewhat less than 10% of orally administered Fluoxetine is excreted from humans unchanged or as <a href="/wiki/Glucuronide" title="Glucuronide">glucuronide</a>.<a href="#cite_note-pmid10674711-318">[318]</a><a href="#cite_note-pmid17160491-319">[319]</a> <div class="mw-heading mw-heading2"><h2 id="See_also">See also</h2>[<a href="/w/index.php?title=Antidepressant&action=edit&section=54" title="Edit section: See also">edit</a>]</div> <style data-mw-deduplicate="TemplateStyles:r1235681985">.mw-parser-output .side-box{margin:4px 0;box-sizing:border-box;border:1px solid #aaa;font-size:88%;line-height:1.25em;background-color:var(--background-color-interactive-subtle,#f8f9fa);display:flow-root}.mw-parser-output .side-box-abovebelow,.mw-parser-output .side-box-text{padding:0.25em 0.9em}.mw-parser-output .side-box-image{padding:2px 0 2px 0.9em;text-align:center}.mw-parser-output .side-box-imageright{padding:2px 0.9em 2px 0;text-align:center}@media(min-width:500px){.mw-parser-output .side-box-flex{display:flex;align-items:center}.mw-parser-output .side-box-text{flex:1;min-width:0}}@media(min-width:720px){.mw-parser-output .side-box{width:238px}.mw-parser-output .side-box-right{clear:right;float:right;margin-left:1em}.mw-parser-output .side-box-left{margin-right:1em}}</style><style data-mw-deduplicate="TemplateStyles:r1237033735">@media print{body.ns-0 .mw-parser-output .sistersitebox{display:none!important}}@media screen{html.skin-theme-clientpref-night .mw-parser-output .sistersitebox img[src*="Wiktionary-logo-en-v2.svg"]{background-color:white}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .sistersitebox img[src*="Wiktionary-logo-en-v2.svg"]{background-color:white}}</style><div class="side-box side-box-right plainlinks sistersitebox"><style data-mw-deduplicate="TemplateStyles:r1126788409">.mw-parser-output .plainlist ol,.mw-parser-output .plainlist ul{line-height:inherit;list-style:none;margin:0;padding:0}.mw-parser-output .plainlist ol li,.mw-parser-output .plainlist ul li{margin-bottom:0}</style> <div class="side-box-flex"> <div class="side-box-image"><a href="/wiki/File:Commons-logo.svg" class="mw-file-description"><img alt="" src="//upload.wikimedia.org/wikipedia/en/thumb/4/4a/Commons-logo.svg/30px-Commons-logo.svg.png" decoding="async" width="30" height="40" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/4/4a/Commons-logo.svg/45px-Commons-logo.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/4/4a/Commons-logo.svg/59px-Commons-logo.svg.png 2x" data-file-width="1024" data-file-height="1376" /></a></div> <div class="side-box-text plainlist">Wikimedia Commons has media related to <a href="https://commons.wikimedia.org/wiki/Category:Antidepressants" class="extiw" title="commons:Category:Antidepressants">Antidepressants</a>.</div></div> </div> <ul><li><a href="/wiki/Antidepressants_in_Japan" title="Antidepressants in Japan">Antidepressants in Japan</a></li> <li><a href="/wiki/Atypical_antidepressant" title="Atypical antidepressant">Atypical antidepressant</a></li> <li><a href="/wiki/Depression_and_natural_therapies" class="mw-redirect" title="Depression and natural therapies">Depression and natural therapies</a></li> <li><a href="/wiki/Depression_in_childhood_and_adolescence" title="Depression in childhood and adolescence">Depression in childhood and adolescence</a></li> <li><a href="/wiki/List_of_investigational_antidepressants" title="List of investigational antidepressants">List of investigational antidepressants</a></li> <li><a href="/wiki/Management_of_depression" title="Management of depression">Management of depression</a></li></ul> <div class="mw-heading mw-heading2"><h2 id="References">References</h2>[<a href="/w/index.php?title=Antidepressant&action=edit&section=55" title="Edit section: References">edit</a>]</div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist"> <div class="mw-references-wrap mw-references-columns"><ol 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ACS Chem Neurosci. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1021%2Facschemneuro.4c00519">10.1021/acschemneuro.4c00519</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587517">11587517</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/39382192">39382192</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=ACS+Chem+Neurosci&rft.atitle=Classics+in+Chemical+Neuroscience%3A+Tianeptine&rft.date=2024-10&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC11587517%23id-name%3DPMC&rft_id=info%3Apmid%2F39382192&rft_id=info%3Adoi%2F10.1021%2Facschemneuro.4c00519&rft.aulast=Nishio&rft.aufirst=Y&rft.au=Lindsley%2C+CW&rft.au=Bender%2C+AM&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC11587517&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAntidepressant" class="Z3988"> </li> <li id="cite_note-Rasmussen2006-196">^ <a href="#cite_ref-Rasmussen2006_196-0">a</a> <a href="#cite_ref-Rasmussen2006_196-1">b</a> <a href="#cite_ref-Rasmussen2006_196-2">c</a> <a href="#cite_ref-Rasmussen2006_196-3">d</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFRasmussen2006" class="citation journal cs1">Rasmussen N (July 2006). 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Prim Care. 38 (1): 41–58. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.pop.2010.11.004">10.1016/j.pop.2010.11.004</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056348">3056348</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/21356420">21356420</a>. <q>In 1919, Japanese chemist Akira Ogata, as part of his effort to prove the structure of ephedrine, reported the synthesis of the closely related compound we now call methamphetamine, and this result was described in the Western literature (Amatsu & Kubota, 1913; Lee, 2011; Ogata, 1920). [...] As a result, when competitors began to consider emulating SKF's success in the late 1930s, they turned to methamphetamine, which had nearly indistinguishable effects but—because its synthesis together with its pharmacological characteristics was published before 1920—was free from patent encumbrance. [...] In any event, by 1940 Benzedrine Sulfate had achieved medical acclaim and quickly growing sales as an antidepressant effective for milder forms of the condition, both in the United States and the United Kingdom. In Germany, the Temmler drug firm quickly copied SKF, marketing methamphetamine (again, unprotected by patents) tablets under the Pervitin brand, with claims that it restored "joy in work" in cases of mild depression around 1938 (Rasmussen, 2006; Steinkamp, 2006).</q></cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Prim+Care&rft.atitle=Stimulant+abuse%3A+pharmacology%2C+cocaine%2C+methamphetamine%2C+treatment%2C+attempts+at+pharmacotherapy&rft.volume=38&rft.issue=1&rft.pages=%3Cspan+class%3D%22nowrap%22%3E41-%3C%2Fspan%3E58&rft.date=2011-03&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3056348%23id-name%3DPMC&rft_id=info%3Apmid%2F21356420&rft_id=info%3Adoi%2F10.1016%2Fj.pop.2010.11.004&rft.aulast=Ciccarone&rft.aufirst=D&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3056348&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAntidepressant" class="Z3988"> </li> <li id="cite_note-Rasmussen2015-198"><a href="#cite_ref-Rasmussen2015_198-0">^</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFRasmussen2015" class="citation journal cs1">Rasmussen N (2015). 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J Psychopharmacol. 27 (6): 479–496. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1177%2F0269881113482532">10.1177/0269881113482532</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666194">3666194</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/23539642">23539642</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=J+Psychopharmacol&rft.atitle=Amphetamine%2C+past+and+present--a+pharmacological+and+clinical+perspective&rft.volume=27&rft.issue=6&rft.pages=%3Cspan+class%3D%22nowrap%22%3E479-%3C%2Fspan%3E496&rft.date=2013-06&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3666194%23id-name%3DPMC&rft_id=info%3Apmid%2F23539642&rft_id=info%3Adoi%2F10.1177%2F0269881113482532&rft.aulast=Heal&rft.aufirst=DJ&rft.au=Smith%2C+SL&rft.au=Gosden%2C+J&rft.au=Nutt%2C+DJ&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3666194&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAntidepressant" class="Z3988"> </li> <li id="cite_note-GG-200">^ <a href="#cite_ref-GG_200-0">a</a> <a href="#cite_ref-GG_200-1">b</a> <a href="#cite_ref-GG_200-2">c</a> <a href="#cite_ref-GG_200-3">d</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBruntonChabnerKnollmann2011" class="citation book cs1">Brunton LL, Chabner B, Knollmann BC, eds. 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Archived from <a rel="nofollow" class="external text" href="http://journals.apa.org/prevention/volume1/pre0010002a.html">the original</a> on 15 July 1998.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Prevention+and+Treatment&rft.atitle=Listening+to+Prozac+but+hearing+placebo%3A+A+meta-analysis+of+antidepressant+medication&rft.volume=1&rft.issue=2&rft.pages=Article+0002a&rft.date=1998-06-26&rft_id=info%3Adoi%2F10.1037%2F1522-3736.1.1.12a&rft.au=Kirsch%2C+I.&rft.au=Sapirstein%2C+G&rft_id=http%3A%2F%2Fjournals.apa.org%2Fprevention%2Fvolume1%2Fpre0010002a.html&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAntidepressant" class="Z3988"> </li> <li id="cite_note-pmid20170046-223"><a href="#cite_ref-pmid20170046_223-0">^</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFKirsch2009" class="citation journal cs1">Kirsch I (2009). "Antidepressants and the placebo response". Epidemiol Psychiatr Soc. 18 (4): 318–22. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1017%2Fs1121189x00000282">10.1017/s1121189x00000282</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/20170046">20170046</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:2166423">2166423</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Epidemiol+Psychiatr+Soc&rft.atitle=Antidepressants+and+the+placebo+response&rft.volume=18&rft.issue=4&rft.pages=%3Cspan+class%3D%22nowrap%22%3E318-%3C%2Fspan%3E22&rft.date=2009&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A2166423%23id-name%3DS2CID&rft_id=info%3Apmid%2F20170046&rft_id=info%3Adoi%2F10.1017%2Fs1121189x00000282&rft.aulast=Kirsch&rft.aufirst=I&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAntidepressant" class="Z3988"> </li> <li id="cite_note-DupuisVeissière2022-224"><a href="#cite_ref-DupuisVeissière2022_224-0">^</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFDupuisVeissière2022" class="citation journal cs1">Dupuis D, Veissière S (October 2022). "Culture, context, and ethics in the therapeutic use of hallucinogens: Psychedelics as active super-placebos?". Transcult Psychiatry. 59 (5): 571–578. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1177%2F13634615221131465">10.1177/13634615221131465</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/36263513">36263513</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Transcult+Psychiatry&rft.atitle=Culture%2C+context%2C+and+ethics+in+the+therapeutic+use+of+hallucinogens%3A+Psychedelics+as+active+super-placebos%3F&rft.volume=59&rft.issue=5&rft.pages=%3Cspan+class%3D%22nowrap%22%3E571-%3C%2Fspan%3E578&rft.date=2022-10&rft_id=info%3Adoi%2F10.1177%2F13634615221131465&rft_id=info%3Apmid%2F36263513&rft.aulast=Dupuis&rft.aufirst=D&rft.au=Veissi%C3%A8re%2C+S&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAntidepressant" class="Z3988"> </li> <li id="cite_note-vanElkYaden2022-225"><a href="#cite_ref-vanElkYaden2022_225-0">^</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFvan_ElkYaden2022" class="citation journal cs1">van Elk M, Yaden DB (September 2022). "Pharmacological, neural, and psychological mechanisms underlying psychedelics: A critical review". Neurosci Biobehav Rev. 140: 104793. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.neubiorev.2022.104793">10.1016/j.neubiorev.2022.104793</a>. <a href="/wiki/Hdl_(identifier)" class="mw-redirect" title="Hdl (identifier)">hdl</a>:<a rel="nofollow" class="external text" href="https://hdl.handle.net/1887%2F3515020">1887/3515020</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/35878791">35878791</a>. <q>In addition, the strong prior expectations that many people have about psychedelics directly contribute to the psychedelic experience and as a consequence it has been suggested that psychedelics may act as a 'super-placebo' (Hartogsohn, 2016). Specifically, strong prior expectations (e.g., that a specific intervention will likely trigger a mystical experience) will increase the likelihood of having e.g., a mystical-type experience (Maij et al., 2019), and this placebo-effect is further boosted by the psychedelic-induced suggestibility.</q></cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Neurosci+Biobehav+Rev&rft.atitle=Pharmacological%2C+neural%2C+and+psychological+mechanisms+underlying+psychedelics%3A+A+critical+review&rft.volume=140&rft.pages=104793&rft.date=2022-09&rft_id=info%3Ahdl%2F1887%2F3515020&rft_id=info%3Apmid%2F35878791&rft_id=info%3Adoi%2F10.1016%2Fj.neubiorev.2022.104793&rft.aulast=van+Elk&rft.aufirst=M&rft.au=Yaden%2C+DB&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAntidepressant" class="Z3988"> </li> <li id="cite_note-PRESCORN2004-226"><a href="#cite_ref-PRESCORN2004_226-0">^</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFPreskornRossStanga2004" class="citation book cs1">Preskorn SH, Ross R, Stanga CY (2004). <a rel="nofollow" class="external text" href="https://books.google.com/books?id=sO_hArhCxwMC&pg=PA241">"Selective Serotonin Reuptake Inhibitors"</a>. 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Archived from <a rel="nofollow" class="external text" href="http://www.science.smith.edu/departments/Biochem/Chm_357/Articles/SSRIs.pdf">the original</a> (PDF) on 23 May 2014.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Pharmacology+%26+Therapeutics&rft.atitle=Pharmacokinetics+of+selective+serotonin+reuptake+inhibitors&rft.volume=85&rft.issue=1&rft.pages=%3Cspan+class%3D%22nowrap%22%3E11-%3C%2Fspan%3E28&rft.date=2000-01&rft_id=info%3Adoi%2F10.1016%2Fs0163-7258%2899%2900048-0&rft_id=info%3Apmid%2F10674711&rft.aulast=Hiemke&rft.aufirst=C&rft.au=H%C3%A4rtter%2C+S&rft_id=http%3A%2F%2Fwww.science.smith.edu%2Fdepartments%2FBiochem%2FChm_357%2FArticles%2FSSRIs.pdf&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAntidepressant" class="Z3988"> </li> <li id="cite_note-pmid17160491-319"><a href="#cite_ref-pmid17160491_319-0">^</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFNentwig2007" class="citation journal cs1">Nentwig G (February 2007). 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Archives of Environmental Contamination and Toxicology. 52 (2): 163–170. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2007ArECT..52..163N">2007ArECT..52..163N</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1007%2Fs00244-005-7190-7">10.1007/s00244-005-7190-7</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/17160491">17160491</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:22309647">22309647</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Archives+of+Environmental+Contamination+and+Toxicology&rft.atitle=Effects+of+pharmaceuticals+on+aquatic+invertebrates.+Part+II%3A+the+antidepressant+drug+Fluoxetine&rft.volume=52&rft.issue=2&rft.pages=%3Cspan+class%3D%22nowrap%22%3E163-%3C%2Fspan%3E170&rft.date=2007-02&rft_id=info%3Adoi%2F10.1007%2Fs00244-005-7190-7&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A22309647%23id-name%3DS2CID&rft_id=info%3Apmid%2F17160491&rft_id=info%3Abibcode%2F2007ArECT..52..163N&rft.aulast=Nentwig&rft.aufirst=G&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAntidepressant" class="Z3988"> </li> </ol></div></div> <div class="mw-heading mw-heading2"><h2 id="Further_reading">Further reading</h2>[<a href="/w/index.php?title=Antidepressant&action=edit&section=56" title="Edit section: Further reading">edit</a>]</div> <ul><li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFStahl1997" class="citation book cs1">Stahl SM (1997). Psychopharmacology of Antidepressants. Informa Healthcare. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-1-85317-513-8" title="Special:BookSources/978-1-85317-513-8"><bdi>978-1-85317-513-8</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Psychopharmacology+of+Antidepressants&rft.pub=Informa+Healthcare&rft.date=1997&rft.isbn=978-1-85317-513-8&rft.aulast=Stahl&rft.aufirst=SM&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAntidepressant" class="Z3988"></li></ul> <div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2>[<a href="/w/index.php?title=Antidepressant&action=edit&section=57" title="Edit section: External links">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1235681985"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1237033735"><div class="side-box side-box-right plainlinks sistersitebox"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"> <div class="side-box-flex"> <div class="side-box-image"><a href="/wiki/File:Wiktionary-logo-en-v2.svg" class="mw-file-description"><img alt="" src="//upload.wikimedia.org/wikipedia/commons/thumb/9/99/Wiktionary-logo-en-v2.svg/40px-Wiktionary-logo-en-v2.svg.png" decoding="async" width="40" height="40" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/9/99/Wiktionary-logo-en-v2.svg/60px-Wiktionary-logo-en-v2.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/9/99/Wiktionary-logo-en-v2.svg/80px-Wiktionary-logo-en-v2.svg.png 2x" data-file-width="512" data-file-height="512" /></a></div> <div class="side-box-text plainlist">Look up <a href="https://en.wiktionary.org/wiki/antidepressant" class="extiw" title="wiktionary:antidepressant">antidepressant</a> in Wiktionary, the free dictionary.</div></div> </div> <ul><li><a href="/wiki/File:Commons-logo.svg" class="mw-file-description"><img alt="" src="//upload.wikimedia.org/wikipedia/en/thumb/4/4a/Commons-logo.svg/12px-Commons-logo.svg.png" decoding="async" width="12" height="16" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/4/4a/Commons-logo.svg/18px-Commons-logo.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/4/4a/Commons-logo.svg/24px-Commons-logo.svg.png 2x" data-file-width="1024" data-file-height="1376" /></a> Media related to <a href="https://commons.wikimedia.org/wiki/Category:Antidepressants" class="extiw" title="commons:Category:Antidepressants">Antidepressants</a> at Wikimedia Commons</li></ul> <div class="CategoryTreeTag" data-ct-options="{"mode":10,"hideprefix":20,"showcount":false,"namespaces":false,"notranslations":false}"><div class="CategoryTreeSection"><div class="CategoryTreeItem"><a class="CategoryTreeToggle" data-ct-title="Antidepressants" aria-expanded="false"></a> <bdi dir="ltr"><a href="/wiki/Category:Antidepressants" title="Category:Antidepressants">Antidepressants</a></bdi></div><div class="CategoryTreeChildren" style="display:none"></div></div></div><div class="CategoryTreeTag" data-ct-options="{"mode":10,"hideprefix":20,"showcount":false,"namespaces":false,"notranslations":false}"><div class="CategoryTreeSection"><div class="CategoryTreeItem"><a class="CategoryTreeToggle" data-ct-title="Drug_classes_defined_by_psychological_effects" aria-expanded="false"></a> <bdi dir="ltr"><a href="/wiki/Category:Drug_classes_defined_by_psychological_effects" title="Category:Drug classes defined by psychological effects">Drug classes defined by psychological effects</a></bdi></div><div class="CategoryTreeChildren" style="display:none"></div></div></div> <div class="CategoryTreeTag" data-ct-options="{"mode":10,"hideprefix":20,"showcount":false,"namespaces":false,"notranslations":false}"><div class="CategoryTreeSection"><div class="CategoryTreeItem"><a class="CategoryTreeToggle" 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.navbox td.hlist dl,.mw-parser-output .navbox td.hlist ol,.mw-parser-output .navbox td.hlist ul{padding:0.125em 0}.mw-parser-output .navbox .navbar{display:block;font-size:100%}.mw-parser-output .navbox-title .navbar{float:left;text-align:left;margin-right:0.5em}body.skin--responsive .mw-parser-output .navbox-image img{max-width:none!important}@media print{body.ns-0 .mw-parser-output .navbox{display:none!important}}</style><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"></div><div role="navigation" class="navbox" aria-labelledby="Antidepressants_(N06A)246" style="padding:3px"><table class="nowraplinks mw-collapsible mw-collapsed navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><style data-mw-deduplicate="TemplateStyles:r1239400231">.mw-parser-output .navbar{display:inline;font-size:88%;font-weight:normal}.mw-parser-output .navbar-collapse{float:left;text-align:left}.mw-parser-output .navbar-boxtext{word-spacing:0}.mw-parser-output .navbar ul{display:inline-block;white-space:nowrap;line-height:inherit}.mw-parser-output .navbar-brackets::before{margin-right:-0.125em;content:"[ "}.mw-parser-output .navbar-brackets::after{margin-left:-0.125em;content:" ]"}.mw-parser-output .navbar li{word-spacing:-0.125em}.mw-parser-output .navbar a>span,.mw-parser-output .navbar a>abbr{text-decoration:inherit}.mw-parser-output .navbar-mini abbr{font-variant:small-caps;border-bottom:none;text-decoration:none;cursor:inherit}.mw-parser-output .navbar-ct-full{font-size:114%;margin:0 7em}.mw-parser-output .navbar-ct-mini{font-size:114%;margin:0 4em}html.skin-theme-clientpref-night .mw-parser-output .navbar li a abbr{color:var(--color-base)!important}@media(prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .navbar li a abbr{color:var(--color-base)!important}}@media print{.mw-parser-output .navbar{display:none!important}}</style><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Antidepressants" title="Template:Antidepressants"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Antidepressants" title="Template talk:Antidepressants"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Antidepressants" title="Special:EditPage/Template:Antidepressants"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Antidepressants_(N06A)246" style="font-size:114%;margin:0 4em"><a class="mw-selflink selflink">Antidepressants</a> (<a href="/wiki/ATC_code_N06#N06A" title="ATC code N06">N06A</a>)</div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks mw-collapsible uncollapsed navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><div id="Specific_reuptake_inhibitors_and/or_receptor_modulators246" style="font-size:114%;margin:0 4em">Specific <a href="/wiki/Reuptake_inhibitor" title="Reuptake inhibitor">reuptake inhibitors</a> and/or <a href="/wiki/Receptor_modulator" title="Receptor modulator">receptor modulators</a></div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Selective_serotonin_reuptake_inhibitors" class="mw-redirect" title="Selective serotonin reuptake inhibitors"><abbr title="Selective serotonin reuptake inhibitors">SSRIs</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Selective serotonin reuptake inhibitors</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Citalopram" title="Citalopram">Citalopram</a></li> <li><a href="/wiki/Escitalopram" title="Escitalopram">Escitalopram</a></li> <li><a href="/wiki/Fluoxetine" title="Fluoxetine">Fluoxetine</a>#</li> <li><a href="/wiki/Fluvoxamine" title="Fluvoxamine">Fluvoxamine</a></li> <li><a href="/wiki/Indalpine" title="Indalpine">Indalpine</a>‡</li> <li><a href="/wiki/Paroxetine" title="Paroxetine">Paroxetine</a></li> <li><a href="/wiki/Sertraline" title="Sertraline">Sertraline</a></li> <li><a href="/wiki/Zimelidine" title="Zimelidine">Zimelidine</a>‡</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Serotonin%E2%80%93norepinephrine_reuptake_inhibitors" class="mw-redirect" title="Serotonin–norepinephrine reuptake inhibitors"><abbr title="Serotonin–norepinephrine reuptake inhibitors">SNRIs</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Serotonin–norepinephrine reuptake inhibitors</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Desvenlafaxine" title="Desvenlafaxine">Desvenlafaxine</a></li> <li><a href="/wiki/Duloxetine" title="Duloxetine">Duloxetine</a></li> <li><a href="/wiki/Levomilnacipran" title="Levomilnacipran">Levomilnacipran</a></li> <li><a href="/wiki/Milnacipran" title="Milnacipran">Milnacipran</a></li> <li><a href="/wiki/Tofenacin" title="Tofenacin">Tofenacin</a></li> <li><a href="/wiki/Venlafaxine" title="Venlafaxine">Venlafaxine</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Norepinephrine_reuptake_inhibitors" class="mw-redirect" title="Norepinephrine reuptake inhibitors"><abbr title="Norepinephrine reuptake inhibitors">NRIs</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Norepinephrine reuptake inhibitors</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Atomoxetine" title="Atomoxetine">Atomoxetine</a></li> <li><a href="/wiki/Reboxetine" title="Reboxetine">Reboxetine</a></li> <li><a href="/wiki/Viloxazine" title="Viloxazine">Viloxazine</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Norepinephrine%E2%80%93dopamine_reuptake_inhibitors" class="mw-redirect" title="Norepinephrine–dopamine reuptake inhibitors"><abbr title="Norepinephrine–dopamine reuptake inhibitors">NDRIs</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Norepinephrine–dopamine reuptake inhibitors</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Amineptine" title="Amineptine">Amineptine</a>‡</li> <li><a href="/wiki/Bupropion" title="Bupropion">Bupropion</a></li> <li><a href="/wiki/Nomifensine" title="Nomifensine">Nomifensine</a>‡</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Noradrenergic_and_specific_serotonergic_antidepressants" class="mw-redirect" title="Noradrenergic and specific serotonergic antidepressants"><abbr title="Noradrenergic and specific serotonergic antidepressants">NaSSAs</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Noradrenergic and specific serotonergic antidepressants</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Mianserin" title="Mianserin">Mianserin</a></li> <li><a href="/wiki/Mirtazapine" title="Mirtazapine">Mirtazapine</a></li> <li><a href="/wiki/Setiptiline" title="Setiptiline">Setiptiline</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Serotonin_antagonist_and_reuptake_inhibitors" class="mw-redirect" title="Serotonin antagonist and reuptake inhibitors"><abbr title="Serotonin antagonist and reuptake inhibitors">SARIs</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Serotonin antagonist and reuptake inhibitors</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Etoperidone" title="Etoperidone">Etoperidone</a></li> <li><a href="/wiki/Nefazodone" title="Nefazodone">Nefazodone</a></li> <li><a href="/wiki/Trazodone" title="Trazodone">Trazodone</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Serotonin_modulator_and_stimulators" class="mw-redirect" title="Serotonin modulator and stimulators"><abbr title="Serotonin modulator and stimulators">SMS</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Serotonin modulator and stimulators</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Vilazodone" title="Vilazodone">Vilazodone</a></li> <li><a href="/wiki/Vortioxetine" title="Vortioxetine">Vortioxetine</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Others</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Agomelatine" title="Agomelatine">Agomelatine</a></li> <li><a href="/wiki/Amisulpride" title="Amisulpride">Amisulpride</a></li> <li><a href="/wiki/Dextromethorphan/bupropion" title="Dextromethorphan/bupropion">Dextromethorphan/bupropion</a></li> <li><a href="/wiki/Esketamine" title="Esketamine">Esketamine</a></li> <li><a href="/wiki/Alpha-Ethyltryptamine" class="mw-redirect" title="Alpha-Ethyltryptamine">Etryptamine</a>‡</li> <li><a href="/wiki/Gepirone" title="Gepirone">Gepirone</a></li> <li><a href="/wiki/Indeloxazine" title="Indeloxazine">Indeloxazine</a></li> <li><a href="/wiki/Flupentixol" title="Flupentixol">Flupentixol</a></li> <li><a href="/wiki/Ketamine" title="Ketamine">Ketamine</a>§</li> <li><a href="/wiki/Medifoxamine" title="Medifoxamine">Medifoxamine</a>‡</li> <li><a href="/wiki/Alpha-Methyltryptamine" class="mw-redirect" title="Alpha-Methyltryptamine">Metryptamine</a>‡</li> <li><a href="/wiki/Oxaflozane" title="Oxaflozane">Oxaflozane</a>‡</li> <li><a href="/wiki/Pivagabine" title="Pivagabine">Pivagabine</a>‡</li> <li><a href="/wiki/Tandospirone" title="Tandospirone">Tandospirone</a></li> <li><a href="/wiki/Teniloxazine" title="Teniloxazine">Teniloxazine</a></li> <li><a href="/wiki/Tianeptine" title="Tianeptine">Tianeptine</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr><tr><td colspan="2" class="navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks mw-collapsible uncollapsed navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><div id="Tricyclic_and_tetracyclic_antidepressants246" style="font-size:114%;margin:0 4em"><a href="/wiki/Tricyclic" title="Tricyclic">Tricyclic</a> and <a href="/wiki/Tetracyclic_antidepressant" title="Tetracyclic antidepressant">tetracyclic antidepressants</a></div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Tricyclic_antidepressants" class="mw-redirect" title="Tricyclic antidepressants"><abbr title="Tricyclic antidepressants">TCAs</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Tricyclic antidepressants</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Amineptine" title="Amineptine">Amineptine</a>‡</li> <li><a href="/wiki/Amitriptyline" title="Amitriptyline">Amitriptyline</a>#</li> <li><a href="/wiki/Amitriptylinoxide" title="Amitriptylinoxide">Amitriptylinoxide</a></li> <li><a href="/wiki/Amoxapine" title="Amoxapine">Amoxapine</a></li> <li><a href="/wiki/Butriptyline" title="Butriptyline">Butriptyline</a>‡</li> <li><a href="/wiki/Clomipramine" title="Clomipramine">Clomipramine</a>#</li> <li><a href="/wiki/Demexiptiline" title="Demexiptiline">Demexiptiline</a>‡</li> <li><a href="/wiki/Desipramine" title="Desipramine">Desipramine</a></li> <li><a href="/wiki/Dibenzepin" title="Dibenzepin">Dibenzepin</a></li> <li><a href="/wiki/Dimetacrine" title="Dimetacrine">Dimetacrine</a>‡</li> <li><a href="/wiki/Dosulepin" title="Dosulepin">Dosulepin</a></li> <li><a href="/wiki/Doxepin" title="Doxepin">Doxepin</a></li> <li><a href="/wiki/Imipramine" title="Imipramine">Imipramine</a></li> <li><a href="/wiki/Imipraminoxide" title="Imipraminoxide">Imipraminoxide</a>‡</li> <li><a href="/wiki/Iprindole" title="Iprindole">Iprindole</a>‡</li> <li><a href="/wiki/Lofepramine" title="Lofepramine">Lofepramine</a></li> <li><a href="/wiki/Melitracen" title="Melitracen">Melitracen</a></li> <li><a href="/wiki/Metapramine" title="Metapramine">Metapramine</a>‡</li> <li><a href="/wiki/Nitroxazepine" title="Nitroxazepine">Nitroxazepine</a></li> <li><a href="/wiki/Nortriptyline" title="Nortriptyline">Nortriptyline</a></li> <li><a href="/wiki/Noxiptiline" title="Noxiptiline">Noxiptiline</a></li> <li><a href="/wiki/Opipramol" title="Opipramol">Opipramol</a></li> <li><a href="/wiki/Pipofezine" title="Pipofezine">Pipofezine</a></li> <li><a href="/wiki/Propizepine" title="Propizepine">Propizepine</a>‡</li> <li><a href="/wiki/Protriptyline" title="Protriptyline">Protriptyline</a></li> <li><a href="/wiki/Quinupramine" title="Quinupramine">Quinupramine</a>‡</li> <li><a href="/wiki/Tianeptine" title="Tianeptine">Tianeptine</a></li> <li><a href="/wiki/Trimipramine" title="Trimipramine">Trimipramine</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Tetracyclic_antidepressants" class="mw-redirect" title="Tetracyclic antidepressants"><abbr title="Tetracyclic antidepressants">TeCAs</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Tetracyclic antidepressants</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Maprotiline" title="Maprotiline">Maprotiline</a></li> <li><a href="/wiki/Mianserin" title="Mianserin">Mianserin</a></li> <li><a href="/wiki/Mirtazapine" title="Mirtazapine">Mirtazapine</a></li> <li><a href="/wiki/Setiptiline" title="Setiptiline">Setiptiline</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Others</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Tiazesim" title="Tiazesim">Tiazesim</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr><tr><td colspan="2" class="navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks mw-collapsible uncollapsed navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><div id="Monoamine_oxidase_inhibitors246" style="font-size:114%;margin:0 4em"><a href="/wiki/Monoamine_oxidase_inhibitor" title="Monoamine oxidase inhibitor">Monoamine oxidase inhibitors</a></div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Non-selective</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>Irreversible: <a href="/wiki/Benmoxin" title="Benmoxin">Benmoxin</a>‡</li> <li><a href="/wiki/Iproclozide" title="Iproclozide">Iproclozide</a>‡</li> <li><a href="/wiki/Iproniazid" title="Iproniazid">Iproniazid</a>‡</li> <li><a href="/wiki/Isocarboxazid" title="Isocarboxazid">Isocarboxazid</a></li> <li><a href="/wiki/Isoniazid" title="Isoniazid">Isoniazid</a>#</li> <li><a href="/wiki/Linezolid" title="Linezolid">Linezolid</a>#</li> <li><a href="/wiki/Mebanazine" title="Mebanazine">Mebanazine</a>‡</li> <li><a href="/wiki/Nialamide" title="Nialamide">Nialamide</a>‡</li> <li><a href="/wiki/Octamoxin" title="Octamoxin">Octamoxin</a>‡</li> <li><a href="/wiki/Phenelzine" title="Phenelzine">Phenelzine</a></li> <li><a href="/wiki/Pheniprazine" title="Pheniprazine">Pheniprazine</a>‡</li> <li><a href="/wiki/Phenoxypropazine" title="Phenoxypropazine">Phenoxypropazine</a>‡</li> <li><a href="/wiki/Pivhydrazine" title="Pivhydrazine">Pivhydrazine</a>‡</li> <li><a href="/wiki/Safrazine" title="Safrazine">Safrazine</a>‡</li> <li><a href="/wiki/Tedizolid" title="Tedizolid">Tedizolid</a></li> <li><a href="/wiki/Tranylcypromine" title="Tranylcypromine">Tranylcypromine</a></li></ul> <ul><li>Reversible: <a href="/wiki/Caroxazone" title="Caroxazone">Caroxazone</a>‡</li></ul> <ul><li>Mixed: <a href="/wiki/Bifemelane" title="Bifemelane">Bifemelane</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Monoamine_oxidase_A" title="Monoamine oxidase A"><abbr title="Monoamine oxidase A">MAOA</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Monoamine oxidase A-selective</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>Reversible: <a href="/wiki/Eprobemide" title="Eprobemide">Eprobemide</a></li> <li><a href="/wiki/Metralindole" title="Metralindole">Metralindole</a></li> <li><a href="/wiki/Minaprine" title="Minaprine">Minaprine</a>‡</li> <li><a href="/wiki/Moclobemide" title="Moclobemide">Moclobemide</a></li> <li><a href="/wiki/Pirlindole" title="Pirlindole">Pirlindole</a></li> <li><a href="/wiki/Tetrindole" title="Tetrindole">Tetrindole</a></li> <li><a href="/wiki/Toloxatone" title="Toloxatone">Toloxatone</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Monoamine_oxidase_B" title="Monoamine oxidase B"><abbr title="Monoamine oxidase B">MAOB</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Monoamine oxidase B-selective</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>Irreversible: <a href="/wiki/Selegiline" title="Selegiline">Selegiline</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr><tr><td colspan="2" class="navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks mw-collapsible uncollapsed navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><div id="Adjunctive_therapies246" style="font-size:114%;margin:0 4em"><a href="/wiki/Adjuvant_therapy" title="Adjuvant therapy">Adjunctive therapies</a></div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Atypical_antipsychotic" title="Atypical antipsychotic">Atypical antipsychotics</a> (<a href="/wiki/Aripiprazole" title="Aripiprazole">aripiprazole</a>, <a href="/wiki/Brexpiprazole" title="Brexpiprazole">brexpiprazole</a>, <a href="/wiki/Lurasidone" title="Lurasidone">lurasidone</a>, <a href="/wiki/Olanzapine" title="Olanzapine">olanzapine</a>, <a href="/wiki/Quetiapine" title="Quetiapine">quetiapine</a>, <a href="/wiki/Risperidone" title="Risperidone">risperidone</a>)</li> <li><a href="/wiki/Buspirone" title="Buspirone">Buspirone</a></li> <li><a href="/wiki/Lithium_(medication)" title="Lithium (medication)">Lithium</a> (<a href="/wiki/Lithium_carbonate" title="Lithium carbonate">lithium carbonate</a>, <a href="/wiki/Lithium_citrate" title="Lithium citrate">lithium citrate</a>)</li> <li><a href="/wiki/Thyroid_hormone" class="mw-redirect" title="Thyroid hormone">Thyroid hormones</a> (<a href="/wiki/Triiodothyronine" title="Triiodothyronine">triiodothyronine</a> (T3), <a href="/wiki/Levothyroxine" title="Levothyroxine">levothyroxine</a> (T4))</li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><td colspan="2" class="navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks mw-collapsible uncollapsed navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><div id="Miscellaneous246" style="font-size:114%;margin:0 4em">Miscellaneous</div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Ademetionine" class="mw-redirect" title="Ademetionine">Ademetionine (<abbr title="S-adenosyl-L-methionine">SAMe</abbr>)</a></li> <li><a href="/wiki/GABAA_receptor_positive_allosteric_modulator" title="GABAA receptor positive allosteric modulator">GABAkine</a> <a href="/wiki/Neurosteroid" title="Neurosteroid">neurosteroids</a> (<a href="/wiki/Allopregnanolone" title="Allopregnanolone">brexanolone</a>, <a href="/wiki/Zuranolone" title="Zuranolone">zuranolone</a>)</li> <li><a href="/wiki/Hypericum_perforatum" title="Hypericum perforatum">Hypericum perforatum (St. John's Wort)</a></li> <li><a href="/wiki/Oxitriptan" title="Oxitriptan">Oxitriptan (<abbr title="5-hydroxytryptophan">5-HTP</abbr>)</a></li> <li><a href="/wiki/Rubidium_chloride" title="Rubidium chloride">Rubidium chloride (RbCl)</a></li> <li><a href="/wiki/Tryptophan" title="Tryptophan">Tryptophan</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><td colspan="2" class="navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"><div class="hlist"> <ul><li>#<a href="/wiki/WHO_Model_List_of_Essential_Medicines" title="WHO Model List of Essential Medicines">WHO-EM</a></li> <li>‡<a href="/wiki/List_of_withdrawn_drugs" title="List of withdrawn drugs">Withdrawn</a> from market</li> <li><a href="/wiki/Clinical_trial" title="Clinical trial">Clinical trials</a>: <ul><li>†<a href="/wiki/Phases_of_clinical_research#Phase_III" title="Phases of clinical research">Phase III</a></li> <li>§Never to phase III</li></ul></li></ul> </div></div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Major_chemical_drug_groups_–_based_upon_the_Anatomical_Therapeutic_Chemical_Classification_System1398" style="padding:3px"><table class="nowraplinks hlist mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Major_drug_groups" title="Template:Major drug groups"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Major_drug_groups" title="Template talk:Major drug groups"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Major_drug_groups" title="Special:EditPage/Template:Major drug groups"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Major_chemical_drug_groups_–_based_upon_the_Anatomical_Therapeutic_Chemical_Classification_System1398" style="font-size:114%;margin:0 4em">Major chemical drug groups – based upon the <a href="/wiki/Anatomical_Therapeutic_Chemical_Classification_System" title="Anatomical Therapeutic Chemical Classification System">Anatomical Therapeutic Chemical Classification System</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Human_gastrointestinal_tract" class="mw-redirect" title="Human gastrointestinal tract">gastrointestinal tract</a> / <a href="/wiki/Metabolism" title="Metabolism">metabolism</a> (<a href="/wiki/ATC_code_A" title="ATC code A">A</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>stomach acid <ul><li><a href="/wiki/Antacid" title="Antacid">Antacids</a></li> <li><a href="/wiki/H2_antagonist" class="mw-redirect" title="H2 antagonist">H2 antagonists</a></li> <li><a href="/wiki/Proton-pump_inhibitor" title="Proton-pump inhibitor">Proton-pump inhibitors</a></li></ul></li> <li><a href="/wiki/Antiemetic" title="Antiemetic">Antiemetics</a></li> <li><a href="/wiki/Laxative" title="Laxative">Laxatives</a></li> <li><a href="/wiki/Antidiarrhoeal" class="mw-redirect" title="Antidiarrhoeal">Antidiarrhoeals</a> / <a href="/wiki/Antipropulsive" title="Antipropulsive">Antipropulsives</a></li> <li><a href="/wiki/Anti-obesity_medication" title="Anti-obesity medication">Anti-obesity drugs</a></li> <li><a href="/wiki/Diabetes_medication" title="Diabetes medication">Diabetes medication</a></li> <li><a href="/wiki/Vitamin" title="Vitamin">Vitamins</a></li> <li><a href="/wiki/Dietary_mineral" class="mw-redirect" title="Dietary mineral">Dietary minerals</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Blood" title="Blood">blood</a> and blood forming organs (<a href="/wiki/ATC_code_B" title="ATC code B">B</a>)</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Antithrombotic" title="Antithrombotic">Antithrombotics</a> <ul><li><a href="/wiki/Antiplatelet_drug" title="Antiplatelet drug">Antiplatelets</a></li> <li><a href="/wiki/Anticoagulant" title="Anticoagulant">Anticoagulants</a></li> <li><a href="/wiki/Thrombolytic_drug" class="mw-redirect" title="Thrombolytic drug">Thrombolytics / fibrinolytics</a></li></ul></li> <li><a href="/wiki/Antihemorrhagic" title="Antihemorrhagic">Antihemorrhagics</a> <ul><li><a href="/wiki/Platelet" title="Platelet">Platelets</a></li> <li><a href="/wiki/Coagulation" title="Coagulation">Coagulants</a></li> <li><a href="/wiki/Antifibrinolytic" title="Antifibrinolytic">Antifibrinolytics</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Circulatory_system" title="Circulatory system">cardiovascular system</a> (<a href="/wiki/ATC_code_C" title="ATC code C">C</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>cardiac therapy / <a href="/wiki/Antianginal" title="Antianginal">antianginals</a> <ul><li><a href="/wiki/Cardiac_glycoside" title="Cardiac glycoside">Cardiac glycosides</a></li> <li><a href="/wiki/Antiarrhythmic_agent" title="Antiarrhythmic agent">Antiarrhythmics</a></li> <li><a href="/wiki/Cardiac_stimulant" title="Cardiac stimulant">Cardiac stimulants</a></li></ul></li> <li><a href="/wiki/Antihypertensive_drug" class="mw-redirect" title="Antihypertensive drug">Antihypertensives</a></li> <li><a href="/wiki/Diuretic" title="Diuretic">Diuretics</a></li> <li><a href="/wiki/Vasodilation" title="Vasodilation">Vasodilators</a></li> <li><a href="/wiki/Beta_blocker" title="Beta blocker">Beta blockers</a></li> <li><a href="/wiki/Calcium_channel_blocker" title="Calcium channel blocker">Calcium channel blockers</a></li> <li><a href="/wiki/Renin%E2%80%93angiotensin_system" title="Renin–angiotensin system">renin–angiotensin system</a> <ul><li><a href="/wiki/ACE_inhibitor" title="ACE inhibitor">ACE inhibitors</a></li> <li><a href="/wiki/Angiotensin_II_receptor_antagonist" class="mw-redirect" title="Angiotensin II receptor antagonist">Angiotensin II receptor antagonists</a></li> <li><a href="/wiki/Renin_inhibitor" title="Renin inhibitor">Renin inhibitors</a></li></ul></li> <li><a href="/wiki/Hypolipidemic_agent" class="mw-redirect" title="Hypolipidemic agent">Antihyperlipidemics</a> <ul><li><a href="/wiki/Statin" title="Statin">Statins</a></li> <li><a href="/wiki/Fibrate" title="Fibrate">Fibrates</a></li> <li><a href="/wiki/Bile_acid_sequestrant" title="Bile acid sequestrant">Bile acid sequestrants</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Human_skin" title="Human skin">skin</a> (<a href="/wiki/ATC_code_D" title="ATC code D">D</a>)</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Emollient" class="mw-redirect" title="Emollient">Emollients</a></li> <li><a href="/wiki/Cicatrizant" class="mw-redirect" title="Cicatrizant">Cicatrizants</a></li> <li><a href="/wiki/Antipruritic" title="Antipruritic">Antipruritics</a></li> <li><a href="/wiki/Antipsoriatic" class="mw-redirect" title="Antipsoriatic">Antipsoriatics</a></li> <li><a href="/wiki/ATC_code_D09" title="ATC code D09">Medicated dressings</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Genitourinary_system" title="Genitourinary system">genitourinary system</a> (<a href="/wiki/ATC_code_G" title="ATC code G">G</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Hormonal_contraception" title="Hormonal contraception">Hormonal contraception</a></li> <li><a href="/wiki/Fertility_medication" title="Fertility medication">Fertility agents</a></li> <li><a href="/wiki/Selective_estrogen_receptor_modulator" title="Selective estrogen receptor modulator">Selective estrogen receptor modulators</a></li> <li><a href="/wiki/Sex_steroid" class="mw-redirect" title="Sex steroid">Sex hormones</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Endocrine_system" title="Endocrine system">endocrine system</a> (<a href="/wiki/ATC_code_H" title="ATC code H">H</a>)</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Hypothalamic%E2%80%93pituitary_hormone" title="Hypothalamic–pituitary hormone">Hypothalamic–pituitary hormones</a></li> <li><a href="/wiki/Corticosteroid" title="Corticosteroid">Corticosteroids</a> <ul><li><a href="/wiki/Glucocorticoid" title="Glucocorticoid">Glucocorticoids</a></li> <li><a href="/wiki/Mineralocorticoid" title="Mineralocorticoid">Mineralocorticoids</a></li></ul></li> <li><a href="/wiki/Sex_steroid" class="mw-redirect" title="Sex steroid">Sex hormones</a></li> <li><a href="/wiki/Thyroid_hormone" class="mw-redirect" title="Thyroid hormone">Thyroid hormones</a> / <a href="/wiki/Antithyroid_agent" title="Antithyroid agent">Antithyroid agents</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Infection" title="Infection">infections</a> and <a href="https://en.wiktionary.org/wiki/infestation" class="extiw" title="wikt:infestation">infestations</a> (<a href="/wiki/ATC_code_J" title="ATC code J">J</a>, <a href="/wiki/ATC_code_P" title="ATC code P">P</a>, <a href="/wiki/ATCvet_code_QI" title="ATCvet code QI">QI</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Antimicrobial" title="Antimicrobial">Antimicrobials</a>: <a href="/wiki/Antibacterial" class="mw-redirect" title="Antibacterial">Antibacterials</a> (<a href="/wiki/Antimycobacterial" title="Antimycobacterial">Antimycobacterials</a>)</li> <li><a href="/wiki/Antifungal_drug" class="mw-redirect" title="Antifungal drug">Antifungals</a></li> <li><a href="/wiki/Antiviral_drug" title="Antiviral drug">Antivirals</a></li> <li><a href="/wiki/Antiparasitic" title="Antiparasitic">Antiparasitics</a> <ul><li><a href="/wiki/Antiprotozoal_agent" class="mw-redirect" title="Antiprotozoal agent">Antiprotozoals</a></li> <li><a href="/wiki/Anthelmintic" title="Anthelmintic">Anthelmintics</a></li> <li><a href="/wiki/Ectoparasiticide" title="Ectoparasiticide">Ectoparasiticides</a></li></ul></li> <li><a href="/wiki/Intravenous_immunoglobulin" class="mw-redirect" title="Intravenous immunoglobulin">Intravenous immunoglobulin</a></li> <li><a href="/wiki/Vaccine" title="Vaccine">Vaccines</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Malignant" class="mw-redirect" title="Malignant">malignant</a> disease (<a href="/wiki/ATC_code_L" title="ATC code L">L01–L02</a>)</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Chemotherapy" title="Chemotherapy">Anticancer agents</a> <ul><li><a href="/wiki/Antimetabolite" title="Antimetabolite">Antimetabolites</a></li> <li><a href="/wiki/Alkylating_antineoplastic_agent" title="Alkylating antineoplastic agent">Alkylating</a></li> <li><a href="/wiki/Spindle_poison" title="Spindle poison">Spindle poisons</a></li> <li><a href="/wiki/Antineoplastic" class="mw-redirect" title="Antineoplastic">Antineoplastic</a></li> <li><a href="/wiki/Topoisomerase_inhibitor" title="Topoisomerase inhibitor">Topoisomerase inhibitors</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Immune_system" title="Immune system">immune</a> disease (<a href="/wiki/ATC_code_L" title="ATC code L">L03–L04</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Immunomodulator" class="mw-redirect" title="Immunomodulator">Immunomodulators</a> <ul><li><a href="/wiki/Immunostimulant" title="Immunostimulant">Immunostimulants</a></li> <li><a href="/wiki/Immunosuppressive_drug" title="Immunosuppressive drug">Immunosuppressants</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Muscle" title="Muscle">muscles</a>, <a href="/wiki/Bone" title="Bone">bones</a>, and <a href="/wiki/Joint" title="Joint">joints</a> (<a href="/wiki/ATC_code_M" title="ATC code M">M</a>)</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Anabolic_steroid" title="Anabolic steroid">Anabolic steroids</a></li> <li><a href="/wiki/Anti-inflammatory" title="Anti-inflammatory">Anti-inflammatories</a> <ul><li><a href="/wiki/Non-steroidal_anti-inflammatory_drug" class="mw-redirect" title="Non-steroidal anti-inflammatory drug">Non-steroidal anti-inflammatory drugs</a></li></ul></li> <li><a href="/wiki/Disease-modifying_antirheumatic_drug" title="Disease-modifying antirheumatic drug">Antirheumatics</a></li> <li><a href="/wiki/Corticosteroid" title="Corticosteroid">Corticosteroids</a></li> <li><a href="/wiki/Muscle_relaxant" title="Muscle relaxant">Muscle relaxants</a></li> <li><a href="/wiki/Bisphosphonate" title="Bisphosphonate">Bisphosphonates</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Human_brain" title="Human brain">brain</a> and <a href="/wiki/Nervous_system" title="Nervous system">nervous system</a> (<a href="/wiki/ATC_code_N" title="ATC code N">N</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Analgesic" title="Analgesic">Analgesics</a></li> <li><a href="/wiki/Anesthetic" title="Anesthetic">Anesthetics</a> <ul><li><a href="/wiki/General_anaesthetic" title="General anaesthetic">General</a></li> <li><a href="/wiki/Local_anesthetic" title="Local anesthetic">Local</a></li></ul></li> <li><a href="/wiki/Anorectic" title="Anorectic">Anorectics</a></li> <li><a href="/wiki/Antihyperkinetic" class="mw-redirect" title="Antihyperkinetic">Anti-ADHD agents</a></li> <li><a href="/wiki/Addiction_medicine" title="Addiction medicine">Antiaddictives</a></li> <li><a href="/wiki/Anticonvulsant" title="Anticonvulsant">Anticonvulsants</a></li> <li><a href="/wiki/Antidementia_drug" class="mw-redirect" title="Antidementia drug">Antidementia agents</a></li> <li><a class="mw-selflink selflink">Antidepressants</a></li> <li><a href="/wiki/Antimigraine_drug" title="Antimigraine drug">Antimigraine agents</a></li> <li><a href="/wiki/Management_of_Parkinson%27s_disease#Medication" title="Management of Parkinson's disease">Antiparkinson agents</a></li> <li><a href="/wiki/Antipsychotic" title="Antipsychotic">Antipsychotics</a></li> <li><a href="/wiki/Anxiolytic" title="Anxiolytic">Anxiolytics</a></li> <li><a href="/wiki/Aphrodisiac" title="Aphrodisiac">Aphrodisiacs</a></li> <li><a href="/wiki/Depressant" title="Depressant">Depressants</a></li> <li><a href="/wiki/Entactogen" class="mw-redirect" title="Entactogen">Entactogens</a></li> <li><a href="/wiki/Entheogen" title="Entheogen">Entheogens</a></li> <li><a href="/wiki/Euphoria" title="Euphoria">Euphoriants</a></li> <li><a href="/wiki/Psychedelics,_dissociatives_and_deliriants" class="mw-redirect" title="Psychedelics, dissociatives and deliriants">Hallucinogens</a> <ul><li><a href="/wiki/Psychedelic_drug" title="Psychedelic drug">Psychedelics</a></li> <li><a href="/wiki/Dissociative" title="Dissociative">Dissociatives</a></li> <li><a href="/wiki/Deliriant" title="Deliriant">Deliriants</a></li></ul></li> <li><a href="/wiki/Hypnotic" title="Hypnotic">Hypnotics</a> / <a href="/wiki/Sedative" title="Sedative">Sedatives</a></li> <li><a href="/wiki/Mood_stabilizer" title="Mood stabilizer">Mood stabilizers</a></li> <li><a href="/wiki/Motivation-enhancing_drug" title="Motivation-enhancing drug">Motivation-enhancing drug</a></li> <li><a href="/wiki/Neuroprotective" class="mw-redirect" title="Neuroprotective">Neuroprotectives</a></li> <li><a href="/wiki/Nootropic" title="Nootropic">Nootropics</a></li> <li><a href="/wiki/Neurotoxin" title="Neurotoxin">Neurotoxins</a></li> <li><a href="/wiki/Orexigenic" class="mw-redirect" title="Orexigenic">Orexigenics</a></li> <li><a href="/wiki/Serenic" title="Serenic">Serenics</a></li> <li><a href="/wiki/Stimulant" title="Stimulant">Stimulants</a></li> <li><a href="/wiki/Wakefulness-promoting_agent" title="Wakefulness-promoting agent">Wakefulness-promoting agents</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Respiratory_system" title="Respiratory system">respiratory system</a> (<a href="/wiki/ATC_code_R" title="ATC code R">R</a>)</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Decongestant" title="Decongestant">Decongestants</a></li> <li><a href="/wiki/Bronchodilator" title="Bronchodilator">Bronchodilators</a></li> <li><a href="/wiki/Cough_medicine" class="mw-redirect" title="Cough medicine">Cough medicines</a></li> <li><a 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title="Antidote">Antidotes</a></li> <li><a href="/wiki/Contrast_medium" class="mw-redirect" title="Contrast medium">Contrast media</a></li> <li><a href="/wiki/Radiopharmacology" title="Radiopharmacology">Radiopharmaceuticals</a></li> <li><a href="/wiki/Dressing_(medicine)" title="Dressing (medicine)">Dressings</a></li> <li><a href="/wiki/Senotherapeutics" class="mw-redirect" title="Senotherapeutics">Senotherapeutics</a></li></ul> </div></td></tr><tr><td class="navbox-abovebelow" colspan="2"><div> <ul><li><img alt="" src="//upload.wikimedia.org/wikipedia/en/thumb/9/96/Symbol_category_class.svg/16px-Symbol_category_class.svg.png" decoding="async" width="16" height="16" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/9/96/Symbol_category_class.svg/23px-Symbol_category_class.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/9/96/Symbol_category_class.svg/31px-Symbol_category_class.svg.png 2x" data-file-width="180" data-file-height="185" /> <a 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