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2024</time></div><h1 class="text-[26px] font-medium leading-8">Postpartum Depression Research Roundup: May 17, 2024</h1><div class="py-3 text-gray-600 md:flex flex-col md:justify-between"><div class="flex flex-col xs:flex-row"><p class="mr-1 self-start">Author(s):</p><div class="flex flex-col xs:flex-row mb-3 md:mb-0"><div class="flex flex-wrap"><span class="text-md mr-2"><a class="text-author text-gray-500 hover:text-primary underline hover:no-underline decoration-gray-400" href="/authors/erin-o-brien">Erin O'Brien</a></span></div></div></div><div class="max-w-full"><div class="flex flex-wrap sm:flex-nowrap items-center w-fit my-2"></div><div class="w-full flex flex-col sm:flex-row justify-between mt-2"><div class="block md:hidden "><div class="mt-2 flex items-center max-w-fit"><button title="Postpartum Depression Research Roundup: May 17, 2024" aria-label="facebook" class="react-share__ShareButton" 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video::-webkit-media-controls-play-button { -webkit-appearance: media-play-button; color: #b8dcf6; } audio::-webkit-media-controls-panel { background-color: white !important; color: #000; } audio::-webkit-media-controls-current-time-display, audio::-webkit-media-controls-time-remaining-display { font-size: 12px; } </style></div></div></div><div class=" lg:w-full flex flex-col lg:flex-row lg:items-center lg:justify-end"></div><div class="w-full flex flex-col px-4 py-4 border-t border-b border-solid border-gray-400 my-4 "><h3 class="text-primary text-xl font-semibold">Key Takeaways</h3><ul class="list-disc px-8"><li class="py-2 "> A cross-sectional study found a 13.6% PPD prevalence, with unhealthy babies and lack of support as key predictors. </li><li class="py-2 "> Heart rate variability alone was insufficient for predicting PPD, but combined models showed high predictive accuracy. </li><li class="py-2 hidden"> Negative perfectionism increased PPD risk by 14%, suggesting the need for identifying and counseling perfectionist individuals.</li></ul><span class="text-xs font-bold text-primary underline cursor-pointer mt-2 ml-4">SHOW MORE</span></div><p class="py-2 mb-2 text-sm italic text-gray-600">What is new in research on postpartum depression?</p><div class="py-2"><div class="blockText_blockContent__TbCXh"><div class=""><div style="width:50%;float:center;max-width:525px;margin:0 auto 1rem;clear:both;cursor:pointer" class=" figure"><div class="flex-none relative text-center"><span style="box-sizing:border-box;display:inline-block;overflow:hidden;width:initial;height:initial;background:none;opacity:1;border:0;margin:0;padding:0;position:relative;max-width:100%"><span style="box-sizing:border-box;display:block;width:initial;height:initial;background:none;opacity:1;border:0;margin:0;padding:0;max-width:100%"><img style="display:block;max-width:100%;width:initial;height:initial;background:none;opacity:1;border:0;margin:0;padding:0" alt="" aria-hidden="true" src="data:image/svg+xml,%3csvg%20xmlns=%27http://www.w3.org/2000/svg%27%20version=%271.1%27%20width=%277896%27%20height=%273168%27/%3e"/></span><img alt="science thodonal_AdobeStock" title="science thodonal_AdobeStock" src="data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7" decoding="async" data-nimg="intrinsic" style="position:absolute;top:0;left:0;bottom:0;right:0;box-sizing:border-box;padding:0;border:none;margin:auto;display:block;width:0;height:0;min-width:100%;max-width:100%;min-height:100%;max-height:100%;object-fit:contain"/><noscript><img alt="science thodonal_AdobeStock" title="science thodonal_AdobeStock" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F66909114ce9d51481bad0717d663d2ddf567d8d9-7896x3168.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=3840&q=75 1x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F66909114ce9d51481bad0717d663d2ddf567d8d9-7896x3168.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=3840&q=75" decoding="async" data-nimg="intrinsic" style="position:absolute;top:0;left:0;bottom:0;right:0;box-sizing:border-box;padding:0;border:none;margin:auto;display:block;width:0;height:0;min-width:100%;max-width:100%;min-height:100%;max-height:100%;object-fit:contain" loading="lazy"/></noscript></span></div><div id="image-caption" class="text-gray-500 italic"><div class="blockText_blockContent__TbCXh"><p class="pb-2">science thodonal_AdobeStock</p></div></div><div class="top-[-100%] block w-[1px] transition-opacity duration-500 ease-in-out opacity-0 overflow-hidden"><img class="m-auto absolute inset-0 max-w-[0%] max-h-[0%] border-[3px] border-solid border-white shadow-[0px_0px_8px_rgba(0,0,0,0.3)] box-border transition ease-in-out duration-500" src="https://cdn.sanity.io/images/0vv8moc6/psychtimes/66909114ce9d51481bad0717d663d2ddf567d8d9-7896x3168.jpg?fit=crop&auto=format"/></div></div><style> #image-caption p{ font-size: 12px; max-width: 525px; margin: 0 auto; text-align: center; } </style></div><p class="pb-2"><em>In this Research Roundup, we explore new studies on the prevalence, predictors, and other factors associated with postpartum depression (PPD).</em></p><p class="pb-2"></p><p class="pb-2"><strong>Exploring the Prevalence and Predictors of PPD</strong></p><p class="pb-2">This analytical cross-sectional study of 674 mothers across 6 countries aimed to explore the prevalence and cognitive, social, and behavioral predictors of PDD. The study’s investigators found that the overall PPD frequency was 13.6%, ranging from 2.3% in Syria to 26% in Ghana. Key predictors included having an unhealthy baby (aOR 11.685) and lack of support (aOR 9.784), while protective factors were being married (aOR 0.141) and being comfortable discussing mental health (aOR 0.369).</p><p class="pb-2">“PPD has many protective and potential factors,” the investigators concluded. “We recommend further research and screenings of PPD for all mothers to promote the well-being of the mothers and create a favorable environment for the newborn and all family members.”</p><p class="pb-2"><strong>Reference</strong></p><p class="pb-2">Amer SA, Zaitoun NA, Abdelsalam HA, et al. <a rel="nofollow noreferrer noopener" target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/38745303/">Exploring predictors and prevalence of postpartum depression among mothers: multinational study</a>. <em>BMC Public Health</em>. 2024;24(1):1308.</p><p class="pb-2"></p><p class="pb-2"><strong>Heart Rate Variability Measures in Pregnancy as Predictors of PPD</strong></p><p class="pb-2">This exploratory study investigated whether heart rate variability (HRV) in late pregnancy could predict PPD and anxiety. HRV was measured in 122 women at week 38 of pregnancy, with depressive and anxiety symptoms assessed at 6 weeks postpartum. Lower HRV was associated with these symptoms, but HRV alone was not predictive. Combined models including HRV and background variables yielded high predictive accuracy (AUC of 0.93 for depression and 0.83 for anxiety), although HRV did not significantly enhance models based solely on psychological measures.</p><p class="pb-2">“The current study does not provide evidence for the use of HRV indices for prediction of PPD and anxiety in women with known pregnancy depression and anxiety,” the investigators concluded. “Further studies investigating the ability of HRV to predict postpartum affective disorders are warranted among women without pregnancy symptoms of depression or anxiety.”</p><p class="pb-2"><strong>Reference</strong></p><p class="pb-2">Eriksson A, Kimmel MC, Furmark T, et al. <a rel="nofollow noreferrer noopener" target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/38744808/">Investigating heart rate variability measures during pregnancy as predictors of postpartum depression and anxiety: an exploratory study</a>. <em>Transl Psychiatry</em>. 2024;14(1):203.</p><p class="pb-2"></p><p class="pb-2"><strong>Connections Between PPD and Positive and Negative Perfectionism</strong></p><p class="pb-2">This study explored factors related to PPD and its connection with perfectionism among 162 mothers in Qom, Iran. The prevalence of PPD was found to be 29.6%, with negative perfectionism increasing the likelihood of PPD by 14%, while positive perfectionism showed no significant correlation. Higher risks of PPD were associated with being a student, having a history of PPD, and unintended pregnancies, whereas factors like multigravidity, breastfeeding, and lack of concern about body image reduced the risk.</p><p class="pb-2">“Since mothers’ negative perfectionism is associated with PPD,” the investigators concluded, “it is recommended to identify perfectionist individuals during pregnancy and after delivery and provide counseling service to them.”</p><p class="pb-2"><strong>Reference</strong></p><p class="pb-2">Rahimi H, Mousavi FS, Rahmanian SA, et al. <a rel="nofollow noreferrer noopener" target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/38726073/">Postpartum depression and its relationship with the positive and negative perfectionism</a>. <em>J Educ Health Promot</em>. 2024;13:110.</p><p class="pb-2"></p><p class="pb-2"><em>Note: This Research Roundup was prepared with the assistance of ChatGPT.</em></p><p class="pb-2"></p><p class="pb-2"><em><strong>Let us hear from you!</strong> Want to share your insights with colleagues on the latest research on postpartum depression or other psychiatric disorders, treatments, and issues? 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The study’s investigators found that the overall PPD frequency was 13.6%, ranging from 2.3% in Syria to 26% in Ghana. Key predictors included having an unhealthy baby (aOR 11.685) and lack of support (aOR 9.784), while protective factors were being married (aOR 0.141) and being comfortable discussing mental health (aOR 0.369).\n\n“PPD has many protective and potential factors,” the investigators concluded. “We recommend further research and screenings of PPD for all mothers to promote the well-being of the mothers and create a favorable environment for the newborn and all family members.”\n\nReference\n\nAmer SA, Zaitoun NA, Abdelsalam HA, et al. Exploring predictors and prevalence of postpartum depression among mothers: multinational study. BMC Public Health. 2024;24(1):1308.\n\n\n\nHeart Rate Variability Measures in Pregnancy as Predictors of PPD\n\nThis exploratory study investigated whether heart rate variability (HRV) in late pregnancy could predict PPD and anxiety. HRV was measured in 122 women at week 38 of pregnancy, with depressive and anxiety symptoms assessed at 6 weeks postpartum. Lower HRV was associated with these symptoms, but HRV alone was not predictive. Combined models including HRV and background variables yielded high predictive accuracy (AUC of 0.93 for depression and 0.83 for anxiety), although HRV did not significantly enhance models based solely on psychological measures.\n\n“The current study does not provide evidence for the use of HRV indices for prediction of PPD and anxiety in women with known pregnancy depression and anxiety,” the investigators concluded. “Further studies investigating the ability of HRV to predict postpartum affective disorders are warranted among women without pregnancy symptoms of depression or anxiety.”\n\nReference\n\nEriksson A, Kimmel MC, Furmark T, et al. Investigating heart rate variability measures during pregnancy as predictors of postpartum depression and anxiety: an exploratory study. Transl Psychiatry. 2024;14(1):203.\n\n\n\nConnections Between PPD and Positive and Negative Perfectionism\n\nThis study explored factors related to PPD and its connection with perfectionism among 162 mothers in Qom, Iran. The prevalence of PPD was found to be 29.6%, with negative perfectionism increasing the likelihood of PPD by 14%, while positive perfectionism showed no significant correlation. Higher risks of PPD were associated with being a student, having a history of PPD, and unintended pregnancies, whereas factors like multigravidity, breastfeeding, and lack of concern about body image reduced the risk.\n\n“Since mothers’ negative perfectionism is associated with PPD,” the investigators concluded, “it is recommended to identify perfectionist individuals during pregnancy and after delivery and provide counseling service to them.”\n\nReference\n\nRahimi H, Mousavi FS, Rahmanian SA, et al. Postpartum depression and its relationship with the positive and negative perfectionism. J Educ Health Promot. 2024;13:110.\n\n\n\nNote: This Research Roundup was prepared with the assistance of ChatGPT.\n\n\n\nLet us hear from you! Want to share your insights with colleagues on the latest research on postpartum depression or other psychiatric disorders, treatments, and issues? Write to us at PTEditor@mmhgroup.com.\n\n","description":"What is new in research on postpartum depression?","author":[{"@type":"Person","name":"Erin O'Brien"}]}</script></div></div><div class="flex-none w-[300px] z-[9999] relative hidden md:block"><div style="top:5rem" class="sticky custom-spacing"><div class="collapse-container " style="overflow:hidden;max-height:900px;transition:max-height .4s ease-in-out"></div></div></div></div><div id="div-gpt-ad-pixel" style="width:1px;height:1px" class=""></div><noscript><iframe src="https://www.googletagmanager.com/ns.html?id=GTM-5V9L5PL" height="0" width="0" style="display:none;visibility:hidden"></iframe></noscript><div id="footerOuterWrap" class="w-full bg-primary flex flex-col items-center justify-center"><div class="container w-[1340px]"><div id="footerInnerWrap" class="bg-primary w-full py-12"><div class="py-4 pl-4 flex flex-row items-center"><div class="flex flex-row flex-wrap w-[55%] h-full"><div class="w-[33%] p-1 my-0 cursor-pointer 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The study’s investigators found that the overall PPD frequency was 13.6%, ranging from 2.3% in Syria to 26% in Ghana. Key predictors included having an unhealthy baby (aOR 11.685) and lack of support (aOR 9.784), while protective factors were being married (aOR 0.141) and being comfortable discussing mental health (aOR 0.369).","_key":"32a3dd114455"}],"_type":"block","style":"normal","_key":"6630579c43d0","upload_doc":null,"uploadAudio":null},{"_key":"c21888299b00","upload_doc":null,"uploadAudio":null,"medias":null,"markDefs":[],"children":[{"_type":"span","marks":[],"text":"“PPD has many protective and potential factors,” the investigators concluded. “We recommend further research and screenings of PPD for all mothers to promote the well-being of the mothers and create a favorable environment for the newborn and all family members.”","_key":"9f6acefc427c0"}],"_type":"block","style":"normal"},{"children":[{"_key":"1609786388380","_type":"span","marks":["strong"],"text":"Reference"}],"upload_doc":null,"uploadAudio":null,"medias":null,"_type":"block","style":"normal","_key":"d59097d0155a","markDefs":[]},{"_type":"block","style":"normal","_key":"eea98e008ed0","upload_doc":null,"uploadAudio":null,"medias":null,"markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/38745303/","_key":"81172fdd109f"}],"children":[{"_type":"span","marks":[],"text":"Amer SA, Zaitoun NA, Abdelsalam HA, et al. 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HRV was measured in 122 women at week 38 of pregnancy, with depressive and anxiety symptoms assessed at 6 weeks postpartum. Lower HRV was associated with these symptoms, but HRV alone was not predictive. Combined models including HRV and background variables yielded high predictive accuracy (AUC of 0.93 for depression and 0.83 for anxiety), although HRV did not significantly enhance models based solely on psychological measures.","_key":"67f5947595e3"}],"_type":"block","style":"normal","_key":"0754788a30fa"},{"_type":"block","style":"normal","_key":"35d567ee0fa0","upload_doc":null,"uploadAudio":null,"medias":null,"markDefs":[],"children":[{"_type":"span","marks":[],"text":"“The current study does not provide evidence for the use of HRV indices for prediction of PPD and anxiety in women with known pregnancy depression and anxiety,” the investigators concluded. “Further studies investigating the ability of HRV to predict postpartum affective disorders are warranted among women without pregnancy symptoms of depression or anxiety.”","_key":"3486f8884a920"}]},{"style":"normal","upload_doc":null,"uploadAudio":null,"medias":null,"_key":"89a52de52d5b","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Reference","_key":"22145275bd980"}],"_type":"block"},{"_key":"70b82c274139","markDefs":[{"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/38744808/","_key":"7981d5067233","blank":true}],"upload_doc":null,"uploadAudio":null,"medias":null,"children":[{"_type":"span","marks":[],"text":"Eriksson A, Kimmel MC, Furmark T, et al. 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The prevalence of PPD was found to be 29.6%, with negative perfectionism increasing the likelihood of PPD by 14%, while positive perfectionism showed no significant correlation. Higher risks of PPD were associated with being a student, having a history of PPD, and unintended pregnancies, whereas factors like multigravidity, breastfeeding, and lack of concern about body image reduced the risk.","_key":"b813f046224b"}],"_type":"block","style":"normal","upload_doc":null,"uploadAudio":null,"medias":null,"_key":"b065cd68bbd9","markDefs":[]},{"style":"normal","_key":"54645b779963","upload_doc":null,"uploadAudio":null,"medias":null,"markDefs":[],"children":[{"_type":"span","marks":[],"text":"“Since mothers’ negative perfectionism is associated with PPD,” the investigators concluded, “it is recommended to identify perfectionist individuals during pregnancy and after delivery and provide counseling service to them.”","_key":"f166aba757940"}],"_type":"block"},{"upload_doc":null,"uploadAudio":null,"medias":null,"markDefs":[],"children":[{"marks":["strong"],"text":"Reference","_key":"10c0441e487a0","_type":"span"}],"_type":"block","style":"normal","_key":"607c78dd15e8"},{"uploadAudio":null,"medias":null,"_key":"b7fad9c89199","markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/38726073/","_key":"f3f179b0286a"}],"children":[{"marks":[],"text":"Rahimi H, Mousavi FS, Rahmanian SA, et al. 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Schonecker M. Paroxysmal dyskinesia as the effect of megaphen. Article in German. ","_key":"a99d116e581e0","_type":"span"},{"_key":"610973c6b052","_type":"span","marks":["em"],"text":"Nervenarzt"},{"_type":"span","marks":[],"text":". 1957;28(12):550-553.","_key":"1cedfe41f191"}],"_type":"block","style":"normal","_key":"869c99e79eb2"},{"_key":"4d26563ad956","markDefs":[{"_type":"link","href":"https://www.axsome.com/auvelity-prescribing-information.pdf","_key":"92a7fa29e26e"}],"children":[{"marks":[],"text":"2. Auvelity. Prescribing information. Axsome; 2022. Accessed November 11, 2024. 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We hope you enjoy.","_key":"505e9f6a73b8","_type":"span"}],"_type":"block"},{"children":[{"marks":[],"text":"I’m Chris Aiken, the Mood Disorders Section Editor for ","_key":"dfdf9b7a3005","_type":"span"},{"_type":"span","marks":["em"],"text":"Psychiatric Times","_key":"153f3cb4c790"},{"marks":["superscript"],"text":"TM","_key":"4e1162c083bd","_type":"span"},{"_type":"span","marks":[],"text":" and the editor-in-chief of the ","_key":"5bc89361d862"},{"_key":"27999f96f295","_type":"span","marks":["em"],"text":"Carlat Psychiatry Report"},{"_type":"span","marks":[],"text":", and I’m Kellie Newsome, a psychiatric NP and the cohost of the ","_key":"f3f5cd4b23da"},{"text":"Carlat Psychiatry Podcast","_key":"76f7861900c8","_type":"span","marks":["em"]},{"_type":"span","marks":[],"text":".","_key":"e3cfb7c5a28d"}],"_type":"block","style":"normal","_key":"a5857dd88911","markDefs":[]},{"style":"normal","_key":"f185b3ff09da","markDefs":[{"blank":true,"_type":"link","href":"https://www.psychiatrictimes.com/view/blue-light-depression-bipolar-disorder","_key":"9875423f7f6f"},{"blank":true,"_type":"link","href":"https://www.ncbi.nlm.nih.gov/pubmed/23926261","_key":"5821d87ef1f6"}],"children":[{"_type":"span","marks":["strong"],"text":"KELLIE NEWSOME","_key":"9a0f2316a98a0"},{"_type":"span","marks":[],"text":": Evening light worsens sleep and mood, and ","_key":"9a0f2316a98a1"},{"text":"last August","_key":"9a0f2316a98a2","_type":"span","marks":["9875423f7f6f"]},{"text":" we unraveled the biology behind that association. To recap, evening light – particularly the blue wavelength suppresses melatonin, worsening 2 systems that are already fragile in people with mood disorders: sleep and circadian rhythms. In animal studies it even altered the core architecture of the brain – shrinking the dendritic spines that ","_key":"9a0f2316a98a3","_type":"span","marks":[]},{"_type":"span","marks":["5821d87ef1f6"],"text":"help us learn","_key":"19d78f18d668"},{"_type":"span","marks":[],"text":" while we sleep.","_key":"ad5adf21833b"},{"_type":"span","marks":["superscript"],"text":"1","_key":"08cd09f661b3"}],"_type":"block"},{"style":"normal","_key":"74c64a3be23f","markDefs":[{"blank":true,"_type":"link","href":"https://www.ncbi.nlm.nih.gov/pubmed/27226262","_key":"1198bbed81a5"}],"children":[{"text":"But you don’t have to go into the woods and live deliberately to fix this problem. Today, we’ll teach you how to use blue light filters to stabilize the circadian rhythms that regulate mood and sleep, and how to use them in ","_key":"e45918effa9b0","_type":"span","marks":[]},{"marks":["1198bbed81a5"],"text":"dark therapy","_key":"299805087023","_type":"span"},{"marks":[],"text":", a behavioral therapy for mania.","_key":"3575cf901bec","_type":"span"},{"_key":"f2efb30b51eb","_type":"span","marks":["superscript"],"text":"2"}],"_type":"block"},{"_type":"block","style":"normal","_key":"baf9da45e634","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Blue Light and Lunar Cycles","_key":"468b1c6ce26c0"}]},{"style":"normal","_key":"069af0e50d8d","markDefs":[],"children":[{"text":"CHRIS AIKEN","_key":"2dcff61dce8d0","_type":"span","marks":["strong"]},{"_type":"span","marks":[],"text":": There are 2 well-known photoreceptors in the eye. The rods see black and white, and the cones add color vision. But in the 1990s a new photoreceptor was discovered – melanopsin – which only responds to the blue wavelength of light. This photoreceptor doesn’t help us see, but it does regulate our circadian rhythm. In the past, this system worked well because we didn’t have much blue light in the evening. There were candles, starlight, fireplaces – all yellow light.","_key":"2dcff61dce8d1"}],"_type":"block"},{"markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/32252567/","_key":"fe0f92d0923b"}],"children":[{"marks":["strong"],"text":"KELLIE NEWSOME","_key":"943378cefa1b0","_type":"span"},{"marks":[],"text":": Except once a month when the blue moon was full. And it’s no coincidence the word lunatic arose in the middle ages as a term for mental illness. It was believed that some people went into temporary bouts of insanity that followed the lunar cycle – the moon. Seven hundred years later, ","_key":"943378cefa1b1","_type":"span"},{"_type":"span","marks":["fe0f92d0923b"],"text":"reports","_key":"8c8c27f27800"},{"_type":"span","marks":[],"text":" linking the full moon to worsening of psychiatric disorders continue to roll in.","_key":"5c3799391272"},{"marks":["superscript"],"text":"3","_key":"e0312ad21686","_type":"span"}],"_type":"block","style":"normal","_key":"7641e7f4c6d3"},{"style":"normal","_key":"52e54edb5332","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Blue Light Blockers","_key":"22afb4f3c5e90"}],"_type":"block"},{"markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"CHRIS AIKEN","_key":"700b98cbf4f20"},{"text":": And in today’s world, every night is a full moon, because cell phones, plasma TVs, and energy efficient bulbs emit a lot of blue light. But technology has also come to the rescue in the form of blue light filtering glasses. These are amber colored glasses, and when you wear them they filter out close to 100% of blue light. They’ve gained popularity among sports figures and celebrities, because wearing them at night improves sleep – which then raises cognitive and athletic performance. But most models out there do not filter enough blue light to make a meaningful difference in psychiatric disorders. We recommend the glasses that were used in the clinical research – and there are 2 types. Some studies have used Uvex glasses, eg Uvex Skyper S1933X and Uvex Ultra-spec 2000, which are $10 to 15 dollars on Amazon.","_key":"700b98cbf4f21","_type":"span","marks":[]},{"_type":"span","marks":["strong"],"text":" ","_key":"285651f59c0a"},{"_type":"span","marks":[],"text":"Another option is lowbluelights.com.","_key":"46a5e7d06801"},{"marks":["strong"],"text":" ","_key":"11eb94fabb93","_type":"span"},{"_type":"span","marks":[],"text":"Any pair on that site will work, and these are much better quality for a higher price, around $50.","_key":"66ffc53ae5a8"}],"_type":"block","style":"normal","_key":"e2613fe8d544"},{"style":"normal","_key":"78d6c8e5e7e9","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"KELLIE NEWSOME","_key":"9c694a732b9b0"},{"_type":"span","marks":[],"text":": I keep a pair of these glasses at my desk for patients to try on. They’re usually surprised to see the world looks quite pleasant through them. They don’t make things dark, but give the world a relaxing, yellow hue. Some patients find them so soothing that I have to warn patients not to wear them during the day, because doing so will flip their circadian rhythm in the wrong direction. When you wear them, your brain will think it’s in pitch darkness, and we only want that effect at night.","_key":"9c694a732b9b1"}],"_type":"block"},{"children":[{"_type":"span","marks":["strong"],"text":"CHRIS AIKEN","_key":"1a20ca278b3c0"},{"_type":"span","marks":[],"text":": Wearing them has real biological effects. When you put them on, your melatonin starts to rise, the same as it does in a ","_key":"1a20ca278b3c1"},{"_type":"span","marks":["12575d5be836"],"text":"pitch-dark room","_key":"390d3a981cbc"},{"_type":"span","marks":[],"text":".","_key":"91282980cf2d"},{"_type":"span","marks":["superscript"],"text":"4","_key":"697961003892"},{"_type":"span","marks":[],"text":" Sometimes patients ask if they can just take melatonin instead, but that doesn’t have the same effect. In a recent randomized controlled trial, taking artificial melatonin did nothing to stabilize mood in bipolar disorder.","_key":"c6dff41e430d"},{"_type":"span","marks":["superscript"],"text":"5","_key":"2599727d60a1"},{"_type":"span","marks":[],"text":" So it’s not enough to have melatonin drizzled on the brain. There are other biological effects involved in pumping out the brain’s indigenous melatonin that are necessary here.","_key":"555373281736"}],"_type":"block","style":"normal","_key":"59a191d00673","markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/15713707/","_key":"12575d5be836"}]},{"_type":"block","style":"normal","_key":"c7d38350dc8b","markDefs":[{"blank":true,"_type":"link","href":"https://www.psychiatrictimes.com/view/blue-light-depression-bipolar-disorder","_key":"c8e9043c10b4"}],"children":[{"_type":"span","marks":[],"text":"If you want to know more about the biological effects of light and darkness listen to our August 2nd podcast on ","_key":"c82b3a5ff5f60"},{"_key":"c82b3a5ff5f61","_type":"span","marks":["c8e9043c10b4"],"text":"Blue Light, Depression, and Bipolar Disorder"},{"_key":"c82b3a5ff5f62","_type":"span","marks":[],"text":". Now, let’s move on to the clinical research."}]},{"_key":"79f7a0caf625","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Origins of Dark Therapy","_key":"d63f0e30dbe20"}],"_type":"block","style":"normal"},{"style":"normal","_key":"d79872329c72","markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/7512910/","_key":"b2f2bf6e15cb"}],"children":[{"marks":["strong"],"text":"KN","_key":"d47c38c77a240","_type":"span"},{"text":": In the 1980s Thomas Wehr, MD, and Norman Rosenthal, MD, made a surprise discovery while working at the National Institute of Mental Health (NIMH). Some patients had worsened depression in the wintertime that improved with light therapy. Their research suggested that circadian rhythms played a strong role in mood disorders, something that was already hinted at by the high rates of insomnia in major depression and the fact that a night without sleep often triggered an episode of mania. So, Wehr turned his attention from morning light to evening darkness. He began with normal subjects and placed them in a pitch-dark room for 14 hours overnight, imitating a dark winter night where the sun goes down at 6 PM and rises at 8 AM. The subjects were a little sleep deprived before the experiment, getting about 7 hours per night, something Wehr thought might be due to the artificial evening light of modern life. After a few weeks in the dark bedroom, their ","_key":"d47c38c77a241","_type":"span","marks":[]},{"text":"sleep stabilized","_key":"5640001f0a8e","_type":"span","marks":["b2f2bf6e15cb"]},{"_type":"span","marks":[],"text":" to 8 hours and 15 minutes per night, closer to the recommended amount an adult needs.","_key":"78be0d17874c"},{"_type":"span","marks":["superscript"],"text":"6,7","_key":"456071b75d5a"}],"_type":"block"},{"children":[{"marks":["strong"],"text":"CA","_key":"248c11caaf5c0","_type":"span"},{"_key":"248c11caaf5c1","_type":"span","marks":[],"text":": Then in 1994 a man came to the NIMH seeking help for rapid cycling bipolar disorder. Most patients don’t call up the NIMH to get help, so we can imagine this man had a pretty bad case. He was a successful engineer with a hyperthymic temperament, but in his 40s he became depressed and started fluoxetine and nortriptyline. He got better on this combination, but then went into a 4-year bout of rapid cycling moods cycling in and out of depression and hypomania every 1 to 2 months. Mood stabilizers did not help, so he came to the NIMH. Wehr knew that sleep disruption could trigger rapid cycling, and he wondered if his super-dark room could stabilize it. He put the patient through the same protocol he used for sleep, placing him in a pitch dark room for 14 hours each night. With this dark therapy, he improved so rapidly that they eased the schedule from 14 hours of darkness to 10 hours each night (10:00 PM to 8:00 AM). He stayed well with that regimen, and that is how dark therapy was "},{"_type":"span","marks":["0ed721ba65fa"],"text":"born","_key":"7b881f4d97bb"},{"_type":"span","marks":[],"text":".","_key":"acda32c28c17"},{"_type":"span","marks":["superscript"],"text":"7","_key":"29d23936e285"}],"_type":"block","style":"normal","_key":"4e8d605914a3","markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/9611672/","_key":"0ed721ba65fa"}]},{"markDefs":[],"children":[{"marks":["strong"],"text":"KN","_key":"28fdb6c254e70","_type":"span"},{"_type":"span","marks":[],"text":": But the treatment didn’t really take off. First, it’s hard to get patients in a pitch-dark room overnight. We’re talking so dark that you can’t see your hands in front of your face. Second, we need more than an intriguing case report to put this into practice. The first problem was resolved in the early 2000s by James Phelps, MD.","_key":"28fdb6c254e71"}],"_type":"block","style":"normal","_key":"52ef0cf3e93f"},{"_key":"78971994f42f","markDefs":[],"children":[{"_type":"span","marks":[],"text":"Phelps was working in private practice in Oregon when he chanced upon 3 discoveries that would open up new therapeutic doors in bipolar disorder. First, he learned about Wehr’s research on dark therapy. Then he learned about the new photoreceptor, melanopsin, that set the circadian rhythm by responding to blue light. He wondered if dark therapy could be accomplished by blocking only the blue wavelength of light, and that brought him to the third piece of the puzzle: blue light filtering glasses. Other fields of medicine had already raised alarms about the hazards of evening blue light (such as increased risk of cancer and heart disease) and a company was manufacturing these to improve sleep and health. Phelps called this ","_key":"9749394b1d240"},{"_key":"9749394b1d241","_type":"span","marks":["em"],"text":"virtual darkness"},{"_type":"span","marks":[],"text":" and tried the glasses out on his patients. For some, the glasses did nothing, but about half of his patients reported their sleep was better when they wore the glasses 1 to 2 hours before bed.","_key":"9749394b1d242"},{"marks":["superscript"],"text":"8","_key":"065994221bfc","_type":"span"}],"_type":"block","style":"normal"},{"style":"normal","_key":"390955093fb9","markDefs":[],"children":[{"_type":"span","marks":[],"text":"He then discovered that welders used the same blue-light filters to protect their eyes at the local welding shop, and this opened the door to more treatments because these factory grade lenses were only $7. Phelps tested them and the fit the bill. ","_key":"03ea9e517e010"},{"_type":"span","marks":["em"],"text":"Consumer Reports ","_key":"572dbf06ea9e"},{"_type":"span","marks":[],"text":"later ran tests of blue light blockers and also concluded that the Uvex safety lenses he was using were among the strongest filters.","_key":"186d9f90286e"}],"_type":"block"},{"style":"normal","_key":"71ea429c2694","markDefs":[],"children":[{"_type":"span","marks":[],"text":"Phelps tested the waters, but the definitive study was a full-scale randomized trial in patients who were hospitalized for mania. In addition to treatment as usual, half wore amber lenses in the evening, and half wore (placebo) gray lenses, until sleeping in a pitch-dark room. The improvements were dramatic over the first week, with a large effect size of 1.9, while the control group barely changed.","_key":"fec10e0ca0740"},{"_type":"span","marks":["superscript"],"text":"2","_key":"8839f67a375e"}],"_type":"block"},{"markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"The Protocol","_key":"1394ceb614ae0"}],"_type":"block","style":"normal","_key":"cc6b6fdc0b3d"},{"children":[{"_type":"span","marks":[],"text":"You don’t need to be in the hospital to do this therapy. Phelps has had success using it in an outpatient practice, and we have as well. Here’s how you do it.","_key":"30bfbe3945da0"}],"_type":"block","style":"normal","_key":"596761a4cde7","markDefs":[]},{"style":"normal","_key":"0c4add95764a","markDefs":[],"children":[{"_type":"span","marks":[],"text":"The original protocol required manic patients to be in either pitch darkness or virtual darkness (that is, with the amber glasses on) for 14 hours, from 6:00 PM to 8:00 AM. It took about a week for the mania to improve, and as it did the protocol was relaxed a bit, from 14 hours per night to 10 hours per night. So instead of putting the glasses on at 6 PM, they’d put them on at 7:00 PM, then 8:00 PM, and for prevention thy would move it to 9 or 10 PM. They don’t wear the glasses while asleep. That’s what the pitch-dark bedroom is for. But they do put them on if they are awake and the lights are on.","_key":"4cd04c50e02d0"}],"_type":"block"},{"children":[{"_type":"span","marks":[],"text":"And the pitch darkness really does matter. Even light as dim as a nightlight on can interfere with melatonin secretion. In a large epidemiologic study of older adults, sleeping with a night light on doubled the risk of depression over 2 years compared to a pitch-dark bedroom.","_key":"da5c4ea963040"},{"_type":"span","marks":["superscript"],"text":"9","_key":"352455f41630"}],"_type":"block","style":"normal","_key":"c3741b08e60d","markDefs":[]},{"markDefs":[{"blank":true,"_type":"link","href":"http://www.shiftshade.com/","_key":"1ce054c35f5b"}],"children":[{"_type":"span","marks":[],"text":"But how do they get their bedroom pitch dark in this electric light world? ","_key":"e1b57027dcc10"},{"_type":"span","marks":["1ce054c35f5b"],"text":"Black out curtains","_key":"e1b57027dcc11"},{"_type":"span","marks":[],"text":", electrical tape over LEDs, towels or draft snakes under doors, or sleeping in the basement. If there is still stray light, patients can also sleep with a good eye mask.","_key":"e1b57027dcc12"}],"_type":"block","style":"normal","_key":"97b2fbfacdec"},{"_key":"8273b2575cc1","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"CA","_key":"d49119795ed50"},{"marks":[],"text":": One problem we run into is patients who feel they can’t sleep without the TV on. Usually the reason is depressive rumination. These patients rely on the TV to distract them from their negative, ruminating thoughts. If that’s the case, we recommend ambient music or boring audiobooks instead. Another problem is patients who are afraid of the dark, such as those with PTSD. Here we have a technological solution. They can use amber colored nightlights that don’t emit any blue light. They are available for around $12.","_key":"d49119795ed51","_type":"span"}],"_type":"block","style":"normal"},{"children":[{"_type":"span","marks":["strong"],"text":"KN","_key":"350baa9963580"},{"text":": One modification we don’t recommend is to rely on blue-light filters on laptops and cell phones. Most devices have a setting that turns down the blue in the evening, and no doubt this is certainly a good thing and we’d recommend it in conjunction with dark therapy, but it doesn’t filter 100% and it isn’t going to take care of the background lights. You can find this feature in your smart phone’s settings, or if you’re using a laptop try downloading f.lux (spell it out) for windows or Candlelight by Oliver Denman for Mac.","_key":"350baa9963581","_type":"span","marks":[]}],"_type":"block","style":"normal","_key":"be6037e19876","markDefs":[]},{"markDefs":[],"children":[{"text":"But what if your patient can’t put the glasses on at 6 PM? Remember the 14-hour protocol was used for hospitalized mania, and they loosened it up as the patient got better. In practice, you might use dark therapy for hypomania, mild mixed states or as an intervention for early signs of mania. In those cases, putting the glasses on 2 hours before bed might be enough.","_key":"4d197f0fc8a80","_type":"span","marks":[]}],"_type":"block","style":"normal","_key":"4686c1580b2e"},{"_type":"block","style":"normal","_key":"e7257a6d8b9d","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"CA","_key":"08f2c9b1d95b0"},{"_type":"span","marks":[],"text":": It’s also important to set up expectations. Tell your patient that dark therapy is going to help stabilize their mood, but it may not help them fall asleep. Here’s an interesting pearl from that controlled trial. The patients who got better with the dark therapy didn’t actually sleep more. They slept a little less than the placebo group, but their sleep did get more regular. It went from sleeping and waking at random times to a more steady, stable circadian pattern.","_key":"08f2c9b1d95b1"},{"_type":"span","marks":["superscript"],"text":"2","_key":"fdeda177bab5"},{"_type":"span","marks":[],"text":" A lot of times patients will give up on dark therapy because they think it is supposed to help them sleep.","_key":"a32bdea71870"}]},{"_key":"b5c98c8d3194","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Dark Therapy for Insomnia","_key":"48c1d1ea6fac0"}],"_type":"block","style":"normal"},{"style":"normal","_key":"e5c617dea0f8","markDefs":[],"children":[{"_key":"c513a824ead30","_type":"span","marks":["strong"],"text":"KN"},{"_type":"span","marks":[],"text":": Dark therapy improves mania, but what does it do to sleep? We found 3 randomized controlled trials that tested them out in insomnia, and they had a large effect, helping patients stay asleep longer, fall asleep earlier, and deepening sleep quality.","_key":"c513a824ead31"},{"marks":["superscript"],"text":"10-12","_key":"8e57359618ec","_type":"span"},{"_type":"span","marks":[],"text":" One of them used the blue light blockers as an adjunct to CBT-insomnia, where half the patients had the behavioral therapy with placebo glasses and half used the blue-light blockers. Not only did sleep improve with the blockers, but so did anxiety and depression.10 Another study looked at performance on cognitive tests after wearing the glasses, and that got better as well, probably because the patients were sleeping better.","_key":"cd9d39970f97"},{"text":"11","_key":"0f8658398107","_type":"span","marks":["superscript"]},{"_type":"span","marks":[],"text":" In the sleep studies, patients put the glasses on 1.5 to 2 hours before bedtime.","_key":"98a0034680a3"}],"_type":"block"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"Blue light blockers have been used successfully in jet lag, and they tend to help night owls fall asleep earlier.","_key":"fa05ef5e016d0"}],"_type":"block","style":"normal","_key":"c7b0aabbd537"},{"style":"normal","_key":"5bbc20f2c723","markDefs":[],"children":[{"text":"CA","_key":"08b9b8d0af4d0","_type":"span","marks":["strong"]},{"_type":"span","marks":[],"text":": I wear them myself and I can attest to that. I’m more patient and have better attention, a little quicker on my feet, the next day if I wore them before bed.","_key":"08b9b8d0af4d1"}],"_type":"block"},{"style":"normal","_key":"8e7e003f8d09","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Dark Therapy for Depression","_key":"e1c47995de9a0"}],"_type":"block"},{"_type":"block","style":"normal","_key":"d00277c9dd9f","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"KN","_key":"1a8bcf789c6c0"},{"_type":"span","marks":[],"text":": Blue light blockers have a big effect in mania and rapid cycling, and for sleep they deepen sleep quality and turn night owls into morning people. But can they help depression? We know from animal studies and epidemiologic studies that blue light causes depression, but when it comes to clinical studies using blue light blockers to treat depression the results are mixed. In that CBT-insomnia study, they did improve depressive symptoms, but those patients had clinical insomnia, not clinical depression.","_key":"1a8bcf789c6c1"},{"_type":"span","marks":["superscript"],"text":"10","_key":"a07fecd7c3f5"},{"_type":"span","marks":[],"text":" Beyond that, we have only 2 controlled trials, 1 positive, 1 negative. The positive one was small (n = 27) and centered on postpartum depression, where nocturnal awakening is the norm. Women who used blue-light blockers and low-blue light bulbs had greater improvements than those who used placebo glasses and bulbs.","_key":"6e47b195828e"},{"_type":"span","marks":["superscript"],"text":"13","_key":"b361669caef5"},{"_type":"span","marks":[],"text":" The negative study was also small (n = 20) and included depressed patients with insomnia. The investigators suspected that the glasses might not have worked because the patients found them uncomfortable and did not wear them as much as they should.","_key":"28351afde38b"},{"_type":"span","marks":["superscript"],"text":"14","_key":"489c274fec81"}]},{"style":"normal","_key":"95648ec7ee55","markDefs":[],"children":[{"text":"Warnings","_key":"8ef4c38d11c10","_type":"span","marks":["strong"]}],"_type":"block"},{"markDefs":[],"children":[{"marks":["strong"],"text":"CA","_key":"e8037cb641160","_type":"span"},{"_type":"span","marks":[],"text":": When worn at night, blue light filters have beneficial, biological effects, but can they have side effects? Nothing major showed up in the studies. Possibly headaches, and there are reports of depression in some patients. This usually improves by putting the glasses on later, say, 7 PM or 8 PM instead of 6 PM. 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","_key":"f690684f295a0","_type":"span","marks":[]},{"_type":"span","marks":["45124289dcea"],"text":"Blue-blocking glasses as additive treatment for mania: a randomized placebo-controlled trial.","_key":"f690684f295a1"},{"_type":"span","marks":[],"text":" ","_key":"f690684f295a2"},{"_type":"span","marks":["em"],"text":"Bipolar Disord","_key":"f690684f295a3"},{"text":". 2016;18(3):221-232.","_key":"f690684f295a4","_type":"span","marks":[]}],"_type":"block","style":"normal"},{"_type":"block","style":"normal","_key":"0998fad1e801","markDefs":[{"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/32252567/","_key":"3884d6ee42b8"}],"children":[{"_type":"span","marks":[],"text":"3. Wang RR, Hao Y, Guo H, et al. 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","_key":"5c883b154b8e0"},{"_type":"span","marks":["56e546bfed16"],"text":"Blocking low-wavelength light prevents nocturnal melatonin suppression with no adverse effect on performance during simulated shift work.","_key":"5c883b154b8e1"},{"text":" ","_key":"5c883b154b8e2","_type":"span","marks":[]},{"text":"J Clin Endocrinol Metab","_key":"5c883b154b8e3","_type":"span","marks":["em"]},{"text":". 2005;90(5):2755-2761.","_key":"5c883b154b8e4","_type":"span","marks":[]}],"_type":"block","style":"normal","_key":"5cb7b6d5d358","markDefs":[{"href":"https://pubmed.ncbi.nlm.nih.gov/15713707/","_key":"56e546bfed16","_type":"link"}]},{"_type":"block","style":"normal","_key":"ace75fc73a52","markDefs":[{"_key":"661b6401c265","_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/32474993/"}],"children":[{"_type":"span","marks":[],"text":"5. Quested DJ, Gibson JC, Sharpley AL, et al. Melatonin In Acute Mania Investigation (MIAMI-UK). 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","_key":"94ff1ad30bae0"},{"_type":"span","marks":["d792a216f0c0"],"text":"Extended sleep in humans in 14 hour nights (LD 10:14): relationship between REM density and spontaneous awakening.","_key":"94ff1ad30bae1"},{"_type":"span","marks":[],"text":" ","_key":"94ff1ad30bae2"},{"_key":"94ff1ad30bae3","_type":"span","marks":["em"],"text":"Electroencephalogr Clin Neurophysiol"},{"_type":"span","marks":[],"text":". 1994;90(4):291-297.","_key":"94ff1ad30bae4"}],"_type":"block","style":"normal","_key":"a2db7ccafcdf"},{"style":"normal","_key":"f3ff2e13b6ea","markDefs":[{"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/9611672/","_key":"a8d7ad388575"}],"children":[{"_type":"span","marks":[],"text":"7. Wehr TA, Turner EH, Shimada JM, et al. ","_key":"f8285e4742170"},{"_key":"f8285e4742171","_type":"span","marks":["a8d7ad388575"],"text":"Treatment of rapidly cycling bipolar patient by using extended bed rest and darkness to stabilize the timing and duration of sleep."},{"_type":"span","marks":[],"text":" ","_key":"f8285e4742172"},{"text":"Biol Psychiatry","_key":"f8285e4742173","_type":"span","marks":["em"]},{"_key":"f8285e4742174","_type":"span","marks":[],"text":". 1998;43(11):822-828."}],"_type":"block"},{"_type":"block","style":"normal","_key":"c9d938860932","markDefs":[{"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/17637502/","_key":"b6de4ee3a9d5"}],"children":[{"_type":"span","marks":[],"text":"8. Phelps J. ","_key":"15cd6439011c0"},{"_type":"span","marks":["b6de4ee3a9d5"],"text":"Dark therapy for bipolar disorder using amber lenses for blue light blockade.","_key":"15cd6439011c1"},{"_type":"span","marks":[],"text":" ","_key":"15cd6439011c2"},{"_type":"span","marks":["em"],"text":"Med Hypotheses. ","_key":"15cd6439011c3"},{"_key":"15cd6439011c4","_type":"span","marks":[],"text":"2008;70(2):224-229."}]},{"children":[{"_type":"span","marks":[],"text":"9. Obayashi K, Saeki K, Kurumatani N. ","_key":"5b92afa3ece60"},{"_type":"span","marks":["6b047725a205"],"text":"Bedroom light exposure at night and the incidence of depressive symptoms: a longitudinal study of the heijo-kyo cohort.","_key":"5b92afa3ece61"},{"_type":"span","marks":[],"text":" ","_key":"5b92afa3ece62"},{"text":"Am J Epidemiol","_key":"5b92afa3ece63","_type":"span","marks":["em"]},{"_key":"5b92afa3ece64","_type":"span","marks":[],"text":". 2018;187(3):427-434."}],"_type":"block","style":"normal","_key":"d5589aa2a9de","markDefs":[{"_type":"link","href":"https://www.ncbi.nlm.nih.gov/pubmed/28992236","_key":"6b047725a205"}]},{"_type":"block","style":"normal","_key":"498c3a744878","markDefs":[{"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/31752544/","_key":"8cd871f52d20"}],"children":[{"text":"10. Janků K, Šmotek M, Fárková E, Kopřivová J. ","_key":"c142486ddec20","_type":"span","marks":[]},{"_type":"span","marks":["8cd871f52d20"],"text":"Block the light and sleep well: Evening blue light filtration as a part of cognitive behavioral therapy for insomnia","_key":"c142486ddec21"},{"marks":[],"text":". ","_key":"c142486ddec22","_type":"span"},{"text":"Chronobiol Int","_key":"c142486ddec23","_type":"span","marks":["em"]},{"_type":"span","marks":[],"text":". 2020;37(2):248-259.","_key":"c142486ddec24"}]},{"children":[{"_type":"span","marks":[],"text":"11. Zimmerman ME, Kim MB, Hale C, et al. ","_key":"75da9db6e8c70"},{"text":"Neuropsychological function response to nocturnal blue light blockage in individuals with symptoms of insomnia: A pilot randomized controlled study.","_key":"75da9db6e8c71","_type":"span","marks":["608d36064d48"]},{"_type":"span","marks":[],"text":" ","_key":"75da9db6e8c72"},{"marks":["em"],"text":"J Int Neuropsychol Soc","_key":"75da9db6e8c73","_type":"span"},{"_type":"span","marks":[],"text":". 2019;25(7):668-677.","_key":"75da9db6e8c74"}],"_type":"block","style":"normal","_key":"5eccf8ceb5d9","markDefs":[{"_key":"608d36064d48","_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/30890197/"}]},{"_key":"b8ae923cc3cc","markDefs":[{"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/29101797/","_key":"19d4af5d4c8c"}],"children":[{"_type":"span","marks":[],"text":"12. Shechter A, Kim EW, St-Onge MP, Westwood AJ. 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","drugMentions":"{\"drug_mentions\": [\"ketamine\", \"benzodiazepine\", \"atypical antipsychotic\", \"antidepressants\", \"SSRI antidepressants\"]}","gptSummary":"In a post-hoc analysis of the ELEKT-D trial, ketamine showed greater efficacy than electroconvulsive therapy (ECT) for outpatients and those with less severe depressive symptoms in treatment-resistant depression (TRD). Inpatients with severe symptoms initially responded better to ECT, but outcomes were similar by treatment end. Baseline characteristics, such as comorbid PTSD and higher premorbid intelligence, favored ECT. Higher BMI was linked to better ketamine response, possibly due to inflammation. Access to treatment, rather than baseline characteristics, may influence the choice between ketamine and ECT.","contentCategory":{"_rev":"snQqhhB4O8T5bi1viURsgs","_type":"contentCategory","name":"Articles","_id":"8bdaa7fc-960a-4b57-b076-75fdce3741bb","_updatedAt":"2020-02-25T09:35:56Z","_createdAt":"2020-02-06T09:15:47Z"},"published":"2024-12-04T16:00:00.000Z","body":[{"asset":{"_ref":"image-a4265bf84e03a48782ce54886f1d4472c34fe99f-1820x1024-jpg","_type":"reference"},"imgcaption":[{"children":[{"_type":"span","marks":[],"text":"Justlight/AdobeStock","_key":"2db5f2366ee40"}],"_type":"block","style":"normal","_key":"24dbc128590a","markDefs":[]}],"alignment":"left","disableTextWrap":false,"disableLightBox":true,"_type":"figure","alt":"depression","widthP":50,"_key":"c892f966d55b"},{"style":"normal","_key":"19e8a58f8ec2","markDefs":[],"children":[{"_key":"e1df7963acee0","_type":"span","marks":[],"text":"Outpatients and those with less severe depressive symptoms improved more with ketamine than electroconvulsive therapy (ECT) in a post-hoc analysis of the ELEKT-D trial"},{"_type":"span","marks":["superscript"],"text":"1","_key":"14f0f39ffeaf"},{"text":" of the interventions for patients with treatment-resistant depression (TRD). Inpatients with more severe symptoms demonstrated greater initial improvement with ECT than ketamine, but those responses were comparable by the end of treatment.","_key":"047948d6e77c","_type":"span","marks":[]}],"_type":"block"},{"style":"normal","_key":"786f970ff63c","markDefs":[],"children":[{"_key":"13e735299fe70","_type":"span","marks":[],"text":""}],"_type":"block"},{"markDefs":[],"children":[{"text":"\"There is decisional uncertainty for patients with TRD and clinicians when selecting between ketamine and ECT,\" observed Manish Jha, MBBS, Center for Depression Research and Clinical Care, Department of Psychiatry, the University of Texas Southwestern Medical Center, Dallas, and colleagues.","_key":"5091d2ac3c9e0","_type":"span","marks":[]}],"_type":"block","style":"normal","_key":"c441dbec6686"},{"markDefs":[],"children":[{"text":"","_key":"63f74561ac590","_type":"span","marks":[]}],"_type":"block","style":"normal","_key":"f4c63e3b4f68"},{"_type":"block","style":"normal","_key":"a5d980b43b22","markDefs":[],"children":[{"_type":"span","marks":[],"text":"\"Therefore, identifying baseline, ie, pretreatment, features that may be associated with differential improvement with ketamine vs ECT may be helpful in shared decision-making approaches for patients with TRD,\" they explained.","_key":"bd8db34c977f0"}]},{"markDefs":[],"children":[{"marks":[],"text":"","_key":"441ffcdb0af60","_type":"span"}],"_type":"block","style":"normal","_key":"f5ff4648eac5"},{"_type":"block","style":"normal","_key":"534519e09716","markDefs":[{"_type":"link","href":"https://www.psychiatrictimes.com/topics/ptsd","_key":"5c10d9412d25","nofollow":true,"blank":true}],"children":[{"_key":"2ce46b8b06ec0","_type":"span","marks":[],"text":"The investigators considered a range of patient characteristics, from previous studies suggesting their potential for differential response to the interventions, including depression severity, cognitive functioning, concurrent use of benzodiazepine or of an atypical antipsychotic, obesity, history of attempted suicide, inpatient vs outpatient status at first treatment, and presence of anxious features or of comorbid "},{"_type":"span","marks":["5c10d9412d25"],"text":"posttraumatic stress disorder","_key":"50fc6c73840a"},{"marks":[],"text":".","_key":"d8d3b0a598b8","_type":"span"}]},{"style":"normal","_key":"7443b666657f","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"2f5d4ddee8960"}],"_type":"block"},{"_key":"ec995720c004","markDefs":[],"children":[{"_type":"span","marks":[],"text":"In discussing the study with ","_key":"185e1bfc58150"},{"_type":"span","marks":["em"],"text":"Psychiatric Times","_key":"185e1bfc58151"},{"_type":"span","marks":[],"text":", Jha explained that the distinction between inpatient and outpatient status reflected more than different levels of symptom severity.","_key":"185e1bfc58152"}],"_type":"block","style":"normal"},{"style":"normal","_key":"ccadd9f3508d","markDefs":[],"children":[{"text":"","_key":"6606db9aeae10","_type":"span","marks":[]}],"_type":"block"},{"markDefs":[],"children":[{"marks":[],"text":"\"I believe that they are overlapping but not redundant, as inpatient hospitalization is often preferred for those with concern for safety risk, such as imminent risk of suicide,” Jha commented. \"However, it is important to recognize that only 10% of the sample in the ELEKT-D study were inpatients, which likely reflects the practice of ECT in the US, where most courses of ECT for non-psychotic, treatment-resistant depression are initiated in outpatient setting.\"","_key":"aa61b027324d0","_type":"span"}],"_type":"block","style":"normal","_key":"5985b9cd7ec1"},{"_type":"block","style":"normal","_key":"c59e0b7968f0","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"3efe1a8690ad0"}]},{"_key":"cc5441bb4403","markDefs":[],"children":[{"_key":"0437e2c0f68e0","_type":"span","marks":["strong"],"text":"Distinguishing Between Responders"}],"_type":"block","style":"normal"},{"_key":"91cd9a6e90f8","markDefs":[],"children":[{"_type":"span","marks":[],"text":"Among the 365 participants in the analysis, 195 were randomized to receive ketamine and 170 to ECT. All had inadequate response to at least 2 courses of antidepressants and had initially been referred for possible ECT. Participants met criteria for major depressive disorder without psychotic features, with the current episode of at least 4 weeks duration and severity corresponding to Montgomery-Åsberg Depression Rating Scale (MADRS) score of \u003e20.","_key":"6a77870751940"}],"_type":"block","style":"normal"},{"markDefs":[],"children":[{"_key":"f8e4cc7897fa0","_type":"span","marks":[],"text":""}],"_type":"block","style":"normal","_key":"512663e1f2b5"},{"_type":"block","style":"normal","_key":"bb2b96a33b39","markDefs":[],"children":[{"_type":"span","marks":[],"text":"The course of ketamine comprised a total of 6 infusions over 3 weeks, with each infusion over 40 minutes containing a subanesthetic dose of 0.5 mg/kg body weight. ECT was administered as a right unilateral ultrabrief pulse width at 6 times the seizure threshold (determined during titration at first visit), in 3 treatments per week for a total of 9 over 3 weeks. The ketamine dosage, and the settings and electrode placements in ECT could be modified as clinically indicated.","_key":"429ccf9631ff0"}]},{"_type":"block","style":"normal","_key":"0e2b7a6a8b38","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"17ee292fe5570"}]},{"_key":"cddd62d692fc","markDefs":[],"children":[{"_type":"span","marks":[],"text":"The primary outcome of the ELEKT-D trial was change from baseline on the Quick Inventory of Depressive Symptomatology (QIDS-SR16). Response was defined as a decrease of at least 50% from baseline at the end of treatment visit, and remission corresponded to a QIDS-SR16 score of \u003c5 and MADRS of \u003c10.","_key":"4b8982eabaf60"}],"_type":"block","style":"normal"},{"_key":"12bd415c45fc","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"322bdd1d5f190"}],"_type":"block","style":"normal"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"The investigators reported that those with less severe symptoms at baseline, corresponding to QIDS-SR16 of \u003c20, and those starting treatment as outpatients had greater score reduction with ketamine (-7.7 and -8.4, respectively) than with ECT (-5.6 and-6.2 respectively). Conversely, inpatients with more severe symptoms marked by higher QIDS-SR15 at baseline responded better initially to ECT (-8.4) than ketamine (-6.7), but the measured improvement with each intervention was similar at the end-of-treatment visit (-9.0 and-9.9, respectively).","_key":"5a5821c585570"}],"_type":"block","style":"normal","_key":"f5a90b6c9a64"},{"children":[{"_key":"92d103895f8b0","_type":"span","marks":[],"text":""}],"_type":"block","style":"normal","_key":"9ec0e291fe75","markDefs":[]},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"Additional characteristics which appeared to favor improvement with ECT over ketamine included comorbid PTSD diagnosis and higher premorbid intelligence, estimated with the North American Adult Reading Test-35 (NAART-35).","_key":"8d8967723f450"}],"_type":"block","style":"normal","_key":"ed8d1f94ba63"},{"style":"normal","_key":"36a68fda674a","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"d7054d9a88040"}],"_type":"block"},{"style":"normal","_key":"edbc5a0c12bc","markDefs":[],"children":[{"text":"\"While ketamine always had numerically higher response and remission rates compared with ECT, the difference between these 2 treatment groups was lower among those with an NAART-35 score of 85 or more,” the investigators reported.","_key":"c1100c32a1d00","_type":"span","marks":[]}],"_type":"block"},{"_type":"block","style":"normal","_key":"56c85a65943c","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"47598b53cf810"}]},{"_key":"92c09aefb4ac","markDefs":[],"children":[{"text":"Among nonstatistically significant, but intriguing numerical trends of differential response was higher BMI, related to obesity, associated with higher likelihood of remission with ketamine. In their mixed-effects model analyses, a higher BMI was also associated with greater reduction in both the QIDS-SR16 and the MADRS with ketamine.","_key":"cb23eb80684d0","_type":"span","marks":[]}],"_type":"block","style":"normal"},{"children":[{"marks":[],"text":"","_key":"f13e2f267e440","_type":"span"}],"_type":"block","style":"normal","_key":"eeaf54d0749b","markDefs":[]},{"_type":"block","style":"normal","_key":"612cfb190768","markDefs":[],"children":[{"marks":[],"text":"\"Given that obesity, as indexed by BMI, is associated with a pro-inflammatory state, I would like to see if elevated c-reactive protein (CRP)—an easy-to-measure and clinically available biomarker of inflammation—is associated with response to ketamine,\" Jha remarked. \"We and others have previously shown","_key":"e91b2a07fc400","_type":"span"},{"_type":"span","marks":["superscript"],"text":"2","_key":"51c1b19984e6"},{"marks":[],"text":" that elevated levels of CRP are associated with poorer outcomes with SSRI antidepressants.\"","_key":"d4bc41344230","_type":"span"}]},{"_type":"block","style":"normal","_key":"5fad4bfd9b11","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"7820d6acad940"}]},{"_type":"block","style":"normal","_key":"ddc9e0930b06","markDefs":[],"children":[{"_key":"58c70156848a0","_type":"span","marks":[],"text":"In the final analysis, choosing between the 2 interventions for patients with TRD may rest more on differences in access than in baseline characteristics, Jha acknowledged. \"In my personal experience, the strongest consideration in making this choice in clinical practice is the availability of off-label IV ketamine infusions at academic medical centers and their coverage by insurance.”"}]},{"_type":"block","style":"normal","_key":"3ef265e1beed","markDefs":[],"children":[{"_key":"1829254ac6730","_type":"span","marks":[],"text":""}]},{"markDefs":[],"children":[{"_key":"082831b17f740","_type":"span","marks":["strong"],"text":"Dr Bender"},{"_type":"span","marks":["em"],"text":" reports on medical innovations and advances in practice and edits presentations for news and professional education publications. 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Marissa's symptoms suggest mixed depression or depression with PTSD, complicating diagnosis and treatment decisions.\n\n• Antidepressants and lamotrigine are considered, with lamotrigine offering better tolerability but less obvious applicability.\n\n• Antidepressant withdrawal and lamotrigine allergy risks are compared, influencing treatment choice.\n\n• Patient education and weighing treatment risks are crucial when diagnosis is uncertain.","body":[{"disableTextWrap":false,"alt":"bipolar","imgcaption":[{"markDefs":[],"children":[{"text":"matiasdelcarmine/AdobeStock","_key":"5027ca70270e0","_type":"span","marks":[]}],"_type":"block","style":"normal","_key":"6cb0638d0561"}],"widthP":48,"alignment":"left","asset":{"_ref":"image-7466224b747025da7c84318fef9678a0f34e2c49-3673x2960-jpg","_type":"reference"},"disableLightBox":true,"_type":"figure","_key":"106a481d4f62"},{"_type":"block","style":"normal","_key":"a22f563e8565","markDefs":[{"_type":"link","href":"https://www.psychiatrictimes.com/topics/major-depressive-disorder","_key":"edf0ac03a5bc","nofollow":true,"blank":true},{"nofollow":true,"blank":true,"_type":"link","href":"https://www.psychiatrictimes.com/topics/sleep-disorders","_key":"4965cd747f01"}],"children":[{"text":"“Marissa” has a history of trauma and ","_key":"7e795a6e1eae0","_type":"span","marks":[]},{"_type":"span","marks":["edf0ac03a5bc"],"text":"major depressive disorder","_key":"5427360ce6b1"},{"text":" (MDD). She reports feeling anxious and struggling with ","_key":"4f0759149411","_type":"span","marks":[]},{"text":"insomnia","_key":"b95fad16d960","_type":"span","marks":["4965cd747f01"]},{"_type":"span","marks":[],"text":". Her partner gently notes that Marissa can be pretty angry sometimes. Marissa could have comorbid MDD and posttraumatic stress disorder (PTSD), or she could have a depressive mixed state (and perhaps PTSD as well). As described in the first essay in this 3-part series, Marissa’s symptoms alone will not differentiate these diagnoses. The last of 4 ways of coping with this diagnostic uncertainty discussed in Part 2, comparing the risks of treatment options, is presented here through Marissa’s case.","_key":"6533e3775a3b"}]},{"_key":"0fba996494ae","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"1ba3bee70f700"}],"_type":"block","style":"normal"},{"style":"normal","_key":"ad2f46951b26","markDefs":[{"_type":"link","href":"https://www.psychiatrictimes.com/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F6516fcf6196099be52f4e555fd8cdbe9b9e604b8-1430x424.jpg%3Ffit%3Dcrop%26auto%3Dformat\u0026w=3840\u0026q=75","_key":"f19d03b3a1df","nofollow":true,"blank":true}],"children":[{"_key":"ecb9243cb3330","_type":"span","marks":[],"text":"The "},{"_type":"span","marks":["strong","f19d03b3a1df"],"text":"Figure","_key":"ecb9243cb3331"},{"_key":"ecb9243cb3332","_type":"span","marks":[],"text":" presents the spectrum of mixed states,"},{"_type":"span","marks":["superscript"],"text":"1","_key":"5d4ecb3a1e11"},{"text":" the diagnostic dilemma, and a way of thinking about treatment options.","_key":"bd12760aed44","_type":"span","marks":[]}],"_type":"block"},{"blank":true,"_type":"figure","_key":"2ca7a4d73fcb","asset":{"_ref":"image-6516fcf6196099be52f4e555fd8cdbe9b9e604b8-1430x424-jpg","_type":"reference"},"disableTextWrap":false,"alt":"Figure. The Spectrum of Mixed States","alignment":"right","disableLightBox":true,"imgcaption":[{"_type":"block","style":"normal","_key":"24f40f8d3240","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Figure. ","_key":"2a364c834dd20"},{"_type":"span","marks":[],"text":"The Spectrum of Mixed States","_key":"cdb60e349dd9"}]}],"widthP":60},{"children":[{"marks":[],"text":"","_key":"92aacbdd3c6c0","_type":"span"}],"_type":"block","style":"normal","_key":"b2deed03ef4f","markDefs":[]},{"children":[{"text":"Suppose Marissa, who is 28 years old, has a cousin with possible bipolar disorder, had her first episode of depression at age 20 and 2 episodes since, one of which occurred shortly after the birth of her 2-year-old daughter. Sertraline made her insomnia much worse, so she stopped it. These features raise the probability of bipolarity, but only weakly vs (for example) a strong family history, earlier age of onset, more frequent episodes, and a more adverse response to sertraline. The diagnostic question remains: mixed depression or depression with ","_key":"36e5351be6e30","_type":"span","marks":[]},{"_type":"span","marks":["c72c831c2bda"],"text":"PTSD","_key":"9cbd42080cbf"},{"_type":"span","marks":[],"text":"?","_key":"f83d429f5c34"}],"_type":"block","style":"normal","_key":"29f6fcdbaca3","markDefs":[{"href":"https://www.psychiatrictimes.com/topics/ptsd","_key":"c72c831c2bda","nofollow":true,"blank":true,"_type":"link"}]},{"_type":"block","style":"normal","_key":"fca1ef6e806c","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"011ba4469c3e0"}]},{"_key":"c723e6fccf17","markDefs":[],"children":[{"_type":"span","marks":[],"text":"After patient education (discussed in Part 2), Marissa understands this differential and prefers a medication approach over psychotherapy (even after digital options are presented). A direct comparison of treatment approaches is warranted.","_key":"2fbdbd75a7e00"}],"_type":"block","style":"normal"},{"style":"normal","_key":"fa84f41ebd4c","markDefs":[],"children":[{"_key":"87cf5f9f67cc0","_type":"span","marks":[],"text":""}],"_type":"block"},{"children":[{"_key":"ad5e1574e2b70","_type":"span","marks":["strong"],"text":"Antidepressants or Lamotrigine?"}],"_type":"block","style":"normal","_key":"2a939ed1a45e","markDefs":[]},{"style":"normal","_key":"03e8bc05f80e","markDefs":[],"children":[{"marks":[],"text":"Antidepressants are an obvious option for Marissa. They have modest benefits in both depression","_key":"543efd4c87450","_type":"span"},{"marks":["superscript"],"text":"2","_key":"2be77bca8ff7","_type":"span"},{"text":" and PTSD.","_key":"6cc301ed211a","_type":"span","marks":[]},{"_type":"span","marks":["superscript"],"text":"3","_key":"bde495c2ec7a"},{"marks":[],"text":" Lamotrigine is not so obvious. Here’s the logic.","_key":"7bdfbeb80edf","_type":"span"}],"_type":"block"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"7bda3815a6030"}],"_type":"block","style":"normal","_key":"43af0cf913eb"},{"_key":"1f193cab6eb9","markDefs":[],"children":[{"_type":"span","marks":[],"text":"Treatment guidelines for mixed states","_key":"806dbdc007950"},{"_type":"span","marks":["strikethrough"],"text":"4","_key":"f4fdb1e69bbd"},{"_type":"span","marks":[],"text":" are based primarily on efficacy in short-term RCTs funded by pharmaceutical companies in their pursuit of US Food and Drug Administration approval. Older medications are less studied. No randomized trials have been conducted for broadly defined mixed states (see Part 1).","_key":"cb53f95426f8"}],"_type":"block","style":"normal"},{"children":[{"_key":"dbf1d41106e50","_type":"span","marks":[],"text":""}],"_type":"block","style":"normal","_key":"b73e150b5645","markDefs":[]},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"Tolerability (adverse effects and long-term risks) frequently determines patients’ choice, rather than highest efficacy, particularly if symptoms are chronic not acute. Lamotrigine has the best tolerability amongst the mood stabilizers with antidepressant effects. (Lurasidone lacks decades of use to fully understand its long-term risks; likewise for lumateperone, cariprazine, and iloperidone. Quetiapine can cause insulin resistance, which appears to contribute to treatment resistance.","_key":"b13a437632a10"},{"_type":"span","marks":["superscript"],"text":"5","_key":"019ccde9bdcb"},{"_key":"2edc7e75dde3","_type":"span","marks":[],"text":" Even low doses of lithium can cause hypothyroidism."},{"_type":"span","marks":["superscript"],"text":"6","_key":"8742b382f81a"},{"text":")","_key":"6a4399bcb80a","_type":"span","marks":[]}],"_type":"block","style":"normal","_key":"03b178c94582"},{"_type":"block","style":"normal","_key":"c69636a57931","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"fc5c7007498e0"}]},{"markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Extrapolating Treatment Options","_key":"8e91f866e7cc0"}],"_type":"block","style":"normal","_key":"cd783dba1c29"},{"_type":"block","style":"normal","_key":"cc6a6ebd7b49","markDefs":[{"href":"https://www.psychiatrictimes.com/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F6516fcf6196099be52f4e555fd8cdbe9b9e604b8-1430x424.jpg%3Ffit%3Dcrop%26auto%3Dformat\u0026w=3840\u0026q=75","_key":"b08e775e8ebd","nofollow":true,"blank":true,"_type":"link"}],"children":[{"marks":[],"text":"As shown in the ","_key":"6aa1edca5d450","_type":"span"},{"_key":"6aa1edca5d451","_type":"span","marks":["strong","b08e775e8ebd"],"text":"Figure"},{"marks":[],"text":", by extrapolating from experience in MDD, antidepressants can be considered for mixed depressions. Likewise, by extrapolating from experience in bipolar II, lamotrigine can also be considered.","_key":"6aa1edca5d452","_type":"span"}]},{"markDefs":[],"children":[{"text":"","_key":"5deb7c538fed0","_type":"span","marks":[]}],"_type":"block","style":"normal","_key":"66ef1f58aae4"},{"_key":"d5b7da354092","markDefs":[],"children":[{"_type":"span","marks":[],"text":"Many practitioners are hesitant to consider lamotrigine unless a history of hypomania or mania is obtained. Indeed, while it makes sense to consider antidepressants for depression comorbid with PTSD or generalized anxiety disorder; there is no obvious reason to consider lamotrigine for these conditions—","_key":"476898db106a0"},{"_key":"476898db106a1","_type":"span","marks":["em"],"text":"except when a depressive mixed state is"},{"_type":"span","marks":[],"text":" ","_key":"476898db106a2"},{"_type":"span","marks":["em"],"text":"equally likely the correct diagnosis","_key":"476898db106a3"},{"_key":"476898db106a4","_type":"span","marks":[],"text":"."}],"_type":"block","style":"normal"},{"_key":"0c404d5d9731","markDefs":[],"children":[{"text":"Marissa has surely heard of antidepressants. The patient education discussed in Part 2 will help her understand why lamotrigine is also an option. Now, compare their risks.","_key":"91f1e5526fb70","_type":"span","marks":[]}],"_type":"block","style":"normal"},{"_type":"block","style":"normal","_key":"d83c9a09f76f","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"1e114e8abd5a0"}]},{"style":"normal","_key":"1393f71c02e9","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Comparing Major Risks","_key":"05edbe0d4a570"}],"_type":"block"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"The efficacy of antidepressants vs lamotrigine in broadly defined mixed states has not been studied. But two tolerability concerns are well known: antidepressant withdrawal and lamotrigine allergy. Understanding these risks may have a strong impact on treatment choice when diagnosis is uncertain.","_key":"44a536ceab3e0"}],"_type":"block","style":"normal","_key":"f4ef953c49dd"},{"children":[{"_type":"span","marks":[],"text":"","_key":"90419e037c460"}],"_type":"block","style":"normal","_key":"5b2d958b5eda","markDefs":[]},{"_type":"block","style":"normal","_key":"20ffdaacc454","markDefs":[],"children":[{"text":"Patients often weigh these risks very differently. For some, hearing the risk of Stevens-Johnson Syndrome (SJS) precludes any further consideration, regardless of how one explains its incidence. For others who may have known someone who struggled to discontinue their antidepressant, concerns about withdrawal might strongly affect their treatment choice.","_key":"d125a9d56d260","_type":"span","marks":[]}]},{"style":"normal","_key":"b5ad5791878c","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"61369c75509e0"}],"_type":"block"},{"style":"normal","_key":"af347c3875db","markDefs":[],"children":[{"marks":["strong"],"text":"Incidence of Severe Antidepressant Withdrawal","_key":"db6bafd86f7c0","_type":"span"}],"_type":"block"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"Different sources estimate very different rates of severe withdrawal. In one podcast interview, academic psychiatrist Michael Thase suggested an incidence of 1% to 2%.","_key":"da877787f1940"},{"_type":"span","marks":["superscript"],"text":"7","_key":"3772e72c011d"},{"_type":"span","marks":[],"text":" Other authors, including those of a review of data published through 2022,","_key":"48aad7c98ca9"},{"_type":"span","marks":["superscript"],"text":"8","_key":"8791886a2187"},{"marks":[],"text":" believe the rate is much higher, at least 10% (Mark Horowitz, personal communication). That review notes important effects of dose, duration of treatment, and differences between antidepressants. Obviously, the definition of “severe” also affects rates.","_key":"f41020550da7","_type":"span"}],"_type":"block","style":"normal","_key":"4e99b7b89be1"},{"children":[{"_type":"span","marks":[],"text":"","_key":"7e8abe0f298e0"}],"_type":"block","style":"normal","_key":"36bf88991a3c","markDefs":[]},{"_key":"1ffc088e8e34","markDefs":[],"children":[{"marks":[],"text":"A 2024 review of 79 studies found a 3% rate of severe withdrawal (higher for venlafaxine, desvenlafaxine and escitalopram).","_key":"be355eecfa340","_type":"span"},{"text":"9","_key":"57374b827bec","_type":"span","marks":["superscript"]},{"marks":[],"text":" Lastly, a post-hoc analysis of a recent randomized trial of antidepressant discontinuation found a rate of significant withdrawal of 16% (4 or more emergent symptoms, but not necessarily “severe”; see Response to a Comment by Horowitz).","_key":"cbd52f6a3b5b","_type":"span"},{"_type":"span","marks":["superscript"],"text":"10","_key":"6e6dace49d60"}],"_type":"block","style":"normal"},{"style":"normal","_key":"096653bbb12c","markDefs":[],"children":[{"text":"","_key":"1f972ea23ec60","_type":"span","marks":[]}],"_type":"block"},{"_type":"block","style":"normal","_key":"6a044b590b38","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Withdrawal vs Stevens-Johnson Syndrome","_key":"1520ab2300ba0"}]},{"_key":"f3e70f58d6b1","markDefs":[],"children":[{"_type":"span","marks":[],"text":"Comparing antidepressant withdrawal and extreme allergic reactions to lamotrigine is obviously like comparing apples and oranges. Nevertheless, for a very rough impression of relative risk, comparing their rates may be useful. Consider first their lowest respective estimates: 1% for withdrawal; a 0.05% incidence of SJS","_key":"1ccc36d511040"},{"_type":"span","marks":["superscript"],"text":"11","_key":"56960fd8153e"},{"_type":"span","marks":[],"text":"; and a 0.05% incidence of death among patients with SJS.","_key":"938fe3ddbf8e"},{"marks":["superscript"],"text":"12","_key":"b9dd11684154","_type":"span"},{"_key":"79cc2f2f0f2c","_type":"span","marks":[],"text":" Using these figures, the rate of severe antidepressant withdrawal is 20 times that of SJS and 400 times the SJS death rate."}],"_type":"block","style":"normal"},{"_type":"block","style":"normal","_key":"66bcb625881c","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"da1b073d72160"}]},{"_type":"block","style":"normal","_key":"2382edceedf9","markDefs":[],"children":[{"text":"Or consider the highest respective estimates: 10% for severe withdrawal, and 1% for SJS (inaccurate, but oft cited on internet sites). Using these figures, severe withdrawal is 100 times more common than SJS and 500 times the SJS death rate. Severe withdrawal has been associated with suicidal ideation, but not death by suicide.","_key":"d84da16105020","_type":"span","marks":[]},{"_key":"54b2dde04a8f","_type":"span","marks":["superscript"],"text":"13"},{"marks":[],"text":" On the other hand, very severe withdrawal can be life-limiting for months to years, as attested by thousands of online accounts.","_key":"b22c4b2610a0","_type":"span"},{"_key":"0792677bf0d5","_type":"span","marks":["superscript"],"text":"14"}]},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"d1245bfe2e6e0"}],"_type":"block","style":"normal","_key":"24d667ac5bc6"},{"style":"normal","_key":"27dcfd896a12","markDefs":[],"children":[{"_type":"span","marks":[],"text":"Marissa has yet to make her decision between these 2 options. 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Stahl SM, Morrissette DA, Faedda G, et al. ","_key":"08c068792bd00"},{"text":"Guidelines for the recognition and management of mixed depression.","_key":"08c068792bd01","_type":"span","marks":["9b26d8748925"]},{"_type":"span","marks":[],"text":" ","_key":"f302efca0013"},{"marks":["em"],"text":"CNS Spectr","_key":"08c068792bd02","_type":"span"},{"_type":"span","marks":[],"text":". 2017;22(2):203-219.","_key":"08c068792bd03"}],"_type":"block","style":"normal","_key":"dceb60e768b1"},{"_type":"block","style":"normal","_key":"b1a15ee73baf","markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/29477251/","_key":"408441d8ddfb"}],"children":[{"_type":"span","marks":[],"text":"2. Cipriani A, Furukawa TA, Salanti G, et al. ","_key":"00fa1fc2fc320"},{"_type":"span","marks":["408441d8ddfb"],"text":"Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.","_key":"00fa1fc2fc321"},{"text":" ","_key":"a20a729eaf83","_type":"span","marks":[]},{"text":"Lancet","_key":"00fa1fc2fc322","_type":"span","marks":["em"]},{"_type":"span","marks":[],"text":". 2018;391(10128):1357-1366.","_key":"00fa1fc2fc323"}]},{"style":"normal","_key":"995a0c827b5e","markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/38869978/","_key":"643d4d15c6c8"}],"children":[{"text":"3. Guidetti C, Feeney A, Hock RS, et al. ","_key":"e0fa411b9d820","_type":"span","marks":[]},{"_type":"span","marks":["643d4d15c6c8"],"text":"Antidepressants in the acute treatment of post-traumatic stress disorder in adults: a systematic review and meta-analysis.","_key":"e0fa411b9d821"},{"marks":[],"text":" ","_key":"f17e3a426898","_type":"span"},{"_key":"e0fa411b9d822","_type":"span","marks":["em"],"text":"Int Clin Psychopharmacol"},{"_type":"span","marks":[],"text":". 2024.","_key":"e0fa411b9d823"}],"_type":"block"},{"_key":"e9e7365f118a","markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/35053835/","_key":"8c739eb8922f"}],"children":[{"text":"4. Natale A, Mineo L, Fusar-Poli L, et al. ","_key":"4eb6be63d1640","_type":"span","marks":[]},{"text":"Mixed depression: a mini-review to guide clinical practice and future research developments.","_key":"4eb6be63d1641","_type":"span","marks":["8c739eb8922f"]},{"_type":"span","marks":[],"text":" ","_key":"8a6883cd96da"},{"_type":"span","marks":["em"],"text":"Brain Sci","_key":"4eb6be63d1642"},{"_type":"span","marks":[],"text":". 2022;12(1):92.","_key":"4eb6be63d1643"}],"_type":"block","style":"normal"},{"markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/35120288/","_key":"ad9727862d87"}],"children":[{"marks":[],"text":"5. Calkin CV, Chengappa KR, Cairns K, et al. ","_key":"39a3f4bdecae0","_type":"span"},{"text":"Treating insulin resistance with metformin as a strategy to improve clinical outcomes in treatment-resistant bipolar depression (the TRIO-BD Study): a randomized, quadruple-masked, placebo-controlled clinical trial.","_key":"39a3f4bdecae1","_type":"span","marks":["ad9727862d87"]},{"text":" ","_key":"f8d36a48ed08","_type":"span","marks":[]},{"_key":"39a3f4bdecae2","_type":"span","marks":["em"],"text":"J Clin Psychiatry"},{"marks":[],"text":". 2022;83(2):21m14022.","_key":"39a3f4bdecae3","_type":"span"}],"_type":"block","style":"normal","_key":"1a16d566767d"},{"style":"normal","_key":"e978bf17a068","markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/37704933/","_key":"5982e74453aa"}],"children":[{"marks":[],"text":"6. Phelps J, Coskey OP. ","_key":"d5b024649e080","_type":"span"},{"_type":"span","marks":["5982e74453aa"],"text":"Low and very low lithium levels: thyroid effects are small but still require monitoring.","_key":"d5b024649e081"},{"_type":"span","marks":[],"text":" ","_key":"ccf7ce065454"},{"_type":"span","marks":["em"],"text":"Bipolar Disord","_key":"d5b024649e082"},{"text":". 2024;26(2):129-135.","_key":"d5b024649e083","_type":"span","marks":[]}],"_type":"block"},{"_key":"87080d705305","markDefs":[],"children":[{"_type":"span","marks":[],"text":"7. Thase M. Webinar, Psychopharmacology Institute. Response to Listener Question. May 7, 2020.","_key":"40755f243fb20"}],"_type":"block","style":"normal"},{"_key":"e89f4f4e6cb7","markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/36513909/","_key":"bd468ed062b3"}],"children":[{"_type":"span","marks":[],"text":"8. Horowitz MA, Framer A, Hengartner MP, et al. ","_key":"9fb2053bb80f0"},{"text":"Estimating risk of antidepressant withdrawal from a review of published data.","_key":"9fb2053bb80f1","_type":"span","marks":["bd468ed062b3"]},{"_type":"span","marks":[],"text":" ","_key":"1a4f8c802cc8"},{"_type":"span","marks":["em"],"text":"CNS Drugs","_key":"9fb2053bb80f2"},{"_type":"span","marks":[],"text":". 2023;37(2):143-157.","_key":"9fb2053bb80f3"}],"_type":"block","style":"normal"},{"markDefs":[{"_type":"link","href":"https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(24)00133-0/fulltext","_key":"d6033e1948a1","blank":true}],"children":[{"_type":"span","marks":[],"text":"9. Henssler J, Schmidt Y, Schmidt U, et al. ","_key":"bb782159fc360"},{"_type":"span","marks":["d6033e1948a1"],"text":"Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis.","_key":"bb782159fc361"},{"text":" Lancet Psychiatry.","_key":"bb782159fc362","_type":"span","marks":["em"]},{"_type":"span","marks":[],"text":" 2024;11(7):526-535.","_key":"bb782159fc363"}],"_type":"block","style":"normal","_key":"2282445ded56"},{"children":[{"text":"10. Kendrick T, Stuart B, Bowers H, et al. ","_key":"99f12ec223830","_type":"span","marks":[]},{"_type":"span","marks":["1de45711ba0a"],"text":"Internet and telephone support for discontinuing long-term antidepressants: the REDUCE cluster randomized trial.","_key":"99f12ec223831"},{"_type":"span","marks":[],"text":" ","_key":"91599962f418"},{"_type":"span","marks":["em"],"text":"JAMA Netw Open.","_key":"99f12ec223832"},{"_type":"span","marks":[],"text":" 2024;7(6):e2418383.","_key":"99f12ec223833"}],"_type":"block","style":"normal","_key":"2009c0d00aac","markDefs":[{"blank":true,"_type":"link","href":"https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820202#google_vignette","_key":"1de45711ba0a"}]},{"markDefs":[{"href":"https://pubmed.ncbi.nlm.nih.gov/28225977/","_key":"bdb6bb48ad81","blank":true,"_type":"link"}],"children":[{"_type":"span","marks":[],"text":"11. Bloom R, Amber KT. ","_key":"b1309b9e34740"},{"marks":["bdb6bb48ad81"],"text":"Identifying the incidence of rash, Stevens-Johnson syndrome and toxic epidermal necrolysis in patients taking lamotrigine: a systematic review of 122 randomized controlled trials.","_key":"b1309b9e34741","_type":"span"},{"_key":"21cbca0aca7a","_type":"span","marks":[],"text":" "},{"text":"An Bras Dermatol. ","_key":"b1309b9e34742","_type":"span","marks":["em"]},{"marks":[],"text":"2017;92(1):139-141.","_key":"b1309b9e34743","_type":"span"}],"_type":"block","style":"normal","_key":"3e8601caaa40"},{"_type":"block","style":"normal","_key":"e7f5a966f0c9","markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/27039263/","_key":"10b35fc637fd"}],"children":[{"text":"12. Hsu DY, Brieva J, Silverberg NB, Silverberg JI. ","_key":"bae383e28fa70","_type":"span","marks":[]},{"_key":"bae383e28fa71","_type":"span","marks":["10b35fc637fd"],"text":"Morbidity and mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis in United States adults."},{"_type":"span","marks":[],"text":" ","_key":"e8fdcc158bad"},{"_key":"bae383e28fa72","_type":"span","marks":["em"],"text":"J Invest Dermatol"},{"_type":"span","marks":[],"text":". 2016;136(7):1387-1397.","_key":"bae383e28fa73"}]},{"style":"normal","_key":"a2ac89e04cf8","markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/38270549/","_key":"6e48007f1402"}],"children":[{"_key":"0827733d682d0","_type":"span","marks":[],"text":"13. Kostic M, Plöder M, Hengartner M, Buzejic J. 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","_key":"ac5f8527d5a10"},{"_type":"span","marks":["7977f3f7de1d"],"text":"https://www.survivingantidepressants.org","_key":"ac5f8527d5a11"}],"_type":"block","style":"normal","_key":"9b630e834357","markDefs":[{"blank":true,"_type":"link","href":"https://www.survivingantidepressants.org","_key":"7977f3f7de1d"}]}],"_id":"d6ba6b71-6f80-43bf-8395-883a2728f7bb","documentGroup":null,"gptSummary":"Marissa's case highlights the diagnostic challenges in distinguishing between mixed depression and depression with PTSD. Her history suggests potential bipolarity, complicating treatment decisions. Antidepressants and lamotrigine are considered, with the latter offering better tolerability but less obvious applicability without hypomania history. The risks of antidepressant withdrawal and lamotrigine allergy, particularly Stevens-Johnson Syndrome, are compared. The article emphasizes the importance of patient education and weighing treatment risks, especially when diagnosis is uncertain. Clinicians should remain open to alternative explanations until effective outcomes are achieved.","audioUrl":"https://s3.us-east-1.amazonaws.com/ai-generated-audios/www.psychiatrictimes.com/d6ba6b71-6f80-43bf-8395-883a2728f7bb_1731357840116.d3bbde24-0373-4319-9cbb-92d3c5c1db5e.mp3","factCheckAuthorMapping":null,"title":"Coping with Diagnostic Uncertainty in Mixed States: Comparing Treatment Risks","articleType":"News","contentCategory":{"_rev":"snQqhhB4O8T5bi1viURsgs","_type":"contentCategory","name":"Articles","_id":"8bdaa7fc-960a-4b57-b076-75fdce3741bb","_updatedAt":"2020-02-25T09:35:56Z","_createdAt":"2020-02-06T09:15:47Z"},"drugMentions":"{\"drug_mentions\": [\"Sertraline\", \"Lamotrigine\", \"Lurasidone\", \"lumateperone\", \"cariprazine\", \"iloperidone\", \"Quetiapine\", \"lithium\", \"venlafaxine\", \"desvenlafaxine\", \"escitalopram\", \"metformin\"]}","url":"coping-with-diagnostic-uncertainty-in-mixed-states-comparing-treatment-risks","_updatedAt":"2024-11-21T16:16:56Z","summary":"Let’s compare treatment risks when managing mixed states. 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