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href="/topics/tech-psychiatry">Technology & Psychiatry</a></li><li class=" text-left m-1 p-2 ml-8 hover:opacity-80 hover:underline hover:text-primary"><a class=" " href="/topics/transcranial-magnetic-stimulation">Transcranial Magnetic Stimulation</a></li></ul></div></div></div><div class="sm:flex w-full hidden text-sm border-menu-border"><p class="my-auto flex font-bold text-primary w-auto ">SPOTLIGHT <span class="font-normal">-</span></p><div id="" class="headers w-[90%] h-5 overflow-hidden flex flex-row flex-wrap undefined my-4 ml-0 z-[9999]"><div class=""><a class="block cursor-pointer text-primary hover:underline px-2 pb-3 hover:text-black border-l border-current pl-auto first:border-none first:pl-0 " href="/topics/major-depressive-disorder"> Major Depressive Disorder </a><div class="mt-4 max-w-[125px]"></div></div><div class=""><a class="block cursor-pointer text-primary hover:underline px-2 pb-3 hover:text-black border-l border-current pl-auto first:border-none first:pl-0 " href="/topics/schizophrenia"> | Schizophrenia/Psychosis </a><div class="mt-4 max-w-[125px]"></div></div><div class=""><a class="block cursor-pointer text-primary hover:underline px-2 pb-3 hover:text-black border-l border-current pl-auto first:border-none first:pl-0 " href="/topics/mental-health-awareness"> | Mental Health Awareness Month </a><div class="mt-4 max-w-[125px]"></div></div></div></div></div></nav><div id="navigating-major-depressive-disorder-mdd-the-role-of-glutamate" class="container mx-auto flex m-1 min-h-[57vh] px-4"><div class="flex-auto w-[calc(100%-300px)] pr-0 md:pr-6 mt-16 sm:mt-0"><div class="m-2 md:my-2 md:ml-2 md:pr-12"><div><div><a class="text-sm font-bold text-primary hover:underline" href="/dialogues/bridging-the-gap-in-mdd-care-rapid-acting-therapies-and-glutamate">Bridging the Gap in MDD Care: Rapid-Acting Therapies and Glutamate </a><span class="text-sm text-gray-500"> : Episode 1</span></div><div class="flex flex-wrap"><p class=" text-primary font-semibold">Opinion</p><div class="h-[16px] border-l-2 border-gray-400 mt-1 mx-1"></div><p class=" text-primary font-semibold">Video</p><div class="h-[16px] border-l-2 border-gray-400 mt-1 mx-1 "></div><time class="text-gray-500 " dateTime="2023-11-29T19:08:18.306">November 29, 2023</time></div><h1 class="text-[26px] font-medium leading-8">Navigating Major Depressive Disorder (MDD): The Role of Glutamate</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/gustavo-alva-md-dfapa">Gustavo Alva, MD, DFAPA</a><span class="mx-1">,</span></span><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/craig-chepke-md-fapa">Craig Chepke, MD, DFAPA, FAPA</a></span></div><button class="text-xs text-gray-500 flex items-center mt-2 xs:mt-0 xs:ml-2">+2 More<span class="ml-1"><svg stroke="currentColor" fill="currentColor" stroke-width="0" viewBox="0 0 512 512" height="1em" width="1em" xmlns="http://www.w3.org/2000/svg"><path d="M256 294.1L383 167c9.4-9.4 24.6-9.4 33.9 0s9.3 24.6 0 34L273 345c-9.1 9.1-23.7 9.3-33.1.7L95 201.1c-4.7-4.7-7-10.9-7-17s2.3-12.3 7-17c9.4-9.4 24.6-9.4 33.9 0l127.1 127z"></path></svg></span></button></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></div></div><div class=" lg:w-full flex flex-col lg:flex-row lg:items-center lg:justify-end"></div><p class="py-2 mb-2 text-sm italic text-gray-600">Experts discuss the significance of glutamate in major depressive disorder, highlighting its links to neuroplasticity and stress.</p><div class="py-2"><div class="blockText_blockContent__TbCXh"><p class="pb-2"></p><div class="relative"><div class="brightcove-fluid" autoplay=""></div></div><div class="pb-8"><div class="w-full flex"><div class="flex-none flex justify-center items-center cursor-pointer" style="width:40px"><svg stroke="currentColor" fill="currentColor" stroke-width="0" viewBox="0 0 512 512" class="text-2xl" height="30" width="30" xmlns="http://www.w3.org/2000/svg"><path d="M256 48C141.1 48 48 141.1 48 256s93.1 208 208 208 208-93.1 208-208S370.9 48 256 48zm43.4 289.1c7.5 7.5 7.5 19.8 0 27.3-3.8 3.8-8.7 5.6-13.6 5.6s-9.9-1.9-13.7-5.7l-94-94.3c-6.9-7.6-6.7-19.3.6-26.6l95.4-95.7c7.5-7.5 19.7-7.6 27.3 0 7.5 7.5 7.6 19.7 0 27.3l-81.9 81 79.9 81.1z"></path></svg></div><div class="flex-auto overflow-x-auto hide-scrollbar mt-4" id="gallery-container"><div id="gallery-inner-container" class="grid grid-rows-1" style="max-width:-80px;grid-template-columns:repeat(16, 0px)"><a href="/view/navigating-major-depressive-disorder-mdd-the-role-of-glutamate" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><div class="bg-black text-white text-xs w-auto px-1 absolute z-50 right-5 top-1">Now Viewing</div><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" 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="" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Faaa0626100191147c4489efc055a8b26f4e54a62-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Faaa0626100191147c4489efc055a8b26f4e54a62-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Faaa0626100191147c4489efc055a8b26f4e54a62-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 1.</span>Navigating Major Depressive Disorder (MDD): The Role of Glutamate</h2></a><a href="/view/glutamate-s-rapid-impact-a-new-approach-to-mdd-management" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" 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="" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F5cd86d1a450d3f62594e4f74f780ebcc8183185b-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F5cd86d1a450d3f62594e4f74f780ebcc8183185b-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F5cd86d1a450d3f62594e4f74f780ebcc8183185b-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 2.</span>Glutamate's Rapid Impact: A New Approach to MDD Management</h2></a><a href="/view/neurotransmitter-ballet-nmda-and-ampa-in-mdd-management" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" 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="" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Fd7cf12a1e3bfb3b6b4a7998aa4e998d1548ab79e-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Fd7cf12a1e3bfb3b6b4a7998aa4e998d1548ab79e-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Fd7cf12a1e3bfb3b6b4a7998aa4e998d1548ab79e-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 3.</span>Neurotransmitter Ballet: NMDA and AMPA in MDD Management</h2></a><a href="/view/cognitive-wellness-the-potential-of-glutamate-modulation-for-mdd" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" 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="" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F62251ea843678f047fcf1204834f4278805c1337-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F62251ea843678f047fcf1204834f4278805c1337-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F62251ea843678f047fcf1204834f4278805c1337-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 4.</span>Cognitive Wellness: The Potential of Glutamate Modulation for MDD</h2></a><a href="/view/targeting-glutamate-receptors-in-mdd-treatment" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" 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="" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Fcdeae9c4a5399f1d093cc5941ec124b84e317a3e-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Fcdeae9c4a5399f1d093cc5941ec124b84e317a3e-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Fcdeae9c4a5399f1d093cc5941ec124b84e317a3e-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 5.</span>Targeting Glutamate Receptors in MDD Treatment</h2></a><a href="/view/hopeful-horizons-the-potential-of-rapid-acting-therapies-in-mdd" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" 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="" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F03ab96d0bc8ed6f12983627bbba2e997e37db8a5-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F03ab96d0bc8ed6f12983627bbba2e997e37db8a5-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F03ab96d0bc8ed6f12983627bbba2e997e37db8a5-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 6.</span>Hopeful Horizons: The Potential of Rapid Acting Therapies in MDD</h2></a><a href="/view/shifting-paradigms-the-future-role-of-rapid-acting-antidepressants" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" 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="" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F2cd0ddcdadd4adab50a527b3bfd3c042ac904dd3-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F2cd0ddcdadd4adab50a527b3bfd3c042ac904dd3-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F2cd0ddcdadd4adab50a527b3bfd3c042ac904dd3-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 7.</span>Shifting Paradigms: The Future Role of Rapid Acting Antidepressants</h2></a><a href="/view/anhedonia-and-cognitive-dysfunction-glutamate-modulation-s-impact" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" 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="" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F91594413ccd75293585836d8d4b2e8769866986d-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F91594413ccd75293585836d8d4b2e8769866986d-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F91594413ccd75293585836d8d4b2e8769866986d-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 8.</span>Anhedonia and Cognitive Dysfunction: Glutamate Modulation's Impact</h2></a><a href="/view/current-landscape-of-rapid-acting-therapies-for-mdd" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" 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="" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Fa3c9831b0d6473fdf94e9a7e3b973c14d06d4454-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Fa3c9831b0d6473fdf94e9a7e3b973c14d06d4454-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Fa3c9831b0d6473fdf94e9a7e3b973c14d06d4454-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 9.</span>Current Landscape of Rapid-Acting Therapies for MDD</h2></a><a href="/view/examining-new-agents-for-mdd-treatment-axs-05-" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" 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="" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F752f2e440e295e4cf4f855916b95dfe35f88d441-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F752f2e440e295e4cf4f855916b95dfe35f88d441-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F752f2e440e295e4cf4f855916b95dfe35f88d441-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 10.</span>Examining New Agents for MDD Treatment (AXS-05)</h2></a><a href="/view/examining-new-agents-for-mdd-treatment-zuranolone-" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" 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="" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F8db9176cf8d0b100020ffdd4078c16504bfd761c-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F8db9176cf8d0b100020ffdd4078c16504bfd761c-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F8db9176cf8d0b100020ffdd4078c16504bfd761c-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 11.</span>Examining New Agents for MDD Treatment (Zuranolone)</h2></a><a href="/view/examining-new-agents-for-mdd-treatment-esketemine-" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" 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="" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F422b4673765b97c3a6b6cc31e495cfcd47d6207d-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F422b4673765b97c3a6b6cc31e495cfcd47d6207d-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F422b4673765b97c3a6b6cc31e495cfcd47d6207d-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 12.</span>Examining New Agents for MDD Treatment (Esketemine) </h2></a><a href="/view/clinical-insights-first-case-analysis-of-mdd" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" 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="" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Fe2ed83fa35ef183605481e56519aefaa4a93d7d3-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Fe2ed83fa35ef183605481e56519aefaa4a93d7d3-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Fe2ed83fa35ef183605481e56519aefaa4a93d7d3-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 13.</span>Clinical Insights: First Case Analysis of MDD</h2></a><a href="/view/responding-with-treatment-clinical-perspectives-on-first-mdd-case" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" 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="" srcSet="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Feafbeae9946c44f4751b1ee97993e1fade381d65-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Feafbeae9946c44f4751b1ee97993e1fade381d65-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Feafbeae9946c44f4751b1ee97993e1fade381d65-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 14.</span>Responding With Treatment: Clinical Perspectives on First MDD Case</h2></a><a href="/view/clinical-insights-second-case-analysis-of-mdd" class="pl-[5px] pr-[5px] text-center relative !no-underline !text-primary" style="width:0px cursor-pointer"><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=%27176%27%20height=%2799%27/%3e"/></span><img alt="" src="data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7" decoding="async" data-nimg="intrinsic" 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/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F5f46c97adc0fd2ef3e2fa4bca8bcaa7579361e87-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&q=75 2x" src="/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2F5f46c97adc0fd2ef3e2fa4bca8bcaa7579361e87-1280x720.jpg%3Ffit%3Dcrop%26auto%3Dformat&w=384&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><h2 class="w-full flex-wrap text-center text-sm text-gray-700"><span class="text-sm text-gray-600 mr-2 font-bold">EP: 16.</span>Final Pearls: Changing Possibilities in MDD Management</h2></a></div></div><div class="flex-none flex justify-center items-center cursor-pointer" style="width:40px"><svg stroke="currentColor" fill="currentColor" stroke-width="0" viewBox="0 0 512 512" class="text-2xl transition ease-in-out hover:scale-110" height="30" width="30" xmlns="http://www.w3.org/2000/svg"><path d="M48 256c0 114.9 93.1 208 208 208s208-93.1 208-208S370.9 48 256 48 48 141.1 48 256zm244.5 0l-81.9-81.1c-7.5-7.5-7.5-19.8 0-27.3s19.8-7.5 27.3 0l95.4 95.7c7.3 7.3 7.5 19.1.6 26.6l-94 94.3c-3.8 3.8-8.7 5.7-13.7 5.7-4.9 0-9.9-1.9-13.6-5.6-7.5-7.5-7.6-19.7 0-27.3l79.9-81z"></path></svg></div></div><style> /* Hide scrollbar for Chrome, Safari and Opera */ .hide-scrollbar::-webkit-scrollbar { display: none; } /* Hide scrollbar for IE, Edge and Firefox */ .hide-scrollbar { -ms-overflow-style: none; /* IE and Edge */ scrollbar-width: none; /* Firefox */ } </style></div><p class="pb-2"><strong>Transcript</strong></p><p class="pb-2"><strong>Gus Alva, MD, DFAPA:</strong> Welcome to this <em>Psychiatric Times</em> presentation titled, “Bridging the Gap in Major Depressive Disorder Care: Rapid-Acting Therapies and Glutamine. I’m Gus Alva. I’m the founder and medical director of ATP Clinical Research in Orange County, California. I am thrilled to be joined today by Craig Chepke, a board-certified psychiatrist at Excel Psychiatric Associates in Huntersville, North Carolina. We’ve got Greg Mattingly, a physician and principal investigator in clinical trials for Midwest Research Group in St. Charles, Missouri. Last but not least, Erin Crown, a certified physician assistant and managing member at Oasis LifeCare in State College, Pennsylvania. In today’s discussion, we will focus on the role of rapid-acting therapies, specifically NMDA receptor modulators, in the management of major depressive disorder. Our conversation will explore the mechanisms that distinguish rapid-acting treatments from traditional antidepressants and major depressive disorder management and foster a better understanding of treatment-resistant depression, and strategies for addressing it. Lastly, we will examine real patient cases, emphasizing the importance of considering individual patient experiences and tailoring care accordingly. Let’s begin. If we consider the fact that glutamate and its presence in the brain is heavily concentrated in different regions like the cortex, cerebellum, hippocampal region, thalamic nuclei, caudate nucleus, which one of you wants to lead off by telling us why it is that glutamate is where it is in the brain? Why does that matter?</p><p class="pb-2"></p><p class="pb-2"><strong>Greg Mattingly, MD:</strong> Glutamate’s the main excitatory chemical in the brain. For neural networks to turn on, glutamate pretty much has to fire. And, Craig, I think it’s like 98% of our synapses are modified by glutamate neurotransmission. The analogy I use quite a bit is it’s kind of like the gas pedal in your car. You can turn on the key, but if the gas pedal doesn’t go, you’re not going to get where you need to be. Glutamate turns on those neural networks and helps them to fire.</p><p class="pb-2"></p><p class="pb-2"><strong>Gus Alva, MD, DFAPA:</strong> Interesting.</p><p class="pb-2"></p><p class="pb-2"><strong>Craig Chepke, MD, DFAPA:</strong> To say where glutamate is in the brain, it’s everywhere. I mean, the whole cortex runs off of glutamate. It’s a glutamate machine, basically. That’s what does the work of the brain.</p><p class="pb-2"></p><p class="pb-2"><strong>Gus Alva, MD, DFAPA:</strong> Erin, your thoughts on that?</p><p class="pb-2"></p><p class="pb-2"><strong>Erin Crown, MHS, PA-C:</strong> A little bit of a different direction. It’s heavily influenced by stress, and we know that we all have a lot of stress in our lives in various ways, and it’s impacted by that. So, bottom line: It’s everywhere and highly impacted by stress and inflammation.</p><p class="pb-2"></p><p class="pb-2"><strong>Greg Mattingly, MD:</strong> Erin said something that’s fascinating, and this is why I went into psychiatry over 30 years ago. Glutamate starts that whole cascade of neural plasticity. So it’s a key component of turning on neural networks, but not just turning on your neural networks, but turning on the ability to survive under stress. Without that, our brain isn’t plastic. It doesn’t grow. It doesn’t sprout. It doesn’t connect with each other. So we’re turning on neural networks. We’re turning on neural plasticity. We’re allowing nerve cells to reach out and grow and connect with each other, especially in times of stress.</p><p class="pb-2"></p><p class="pb-2"><strong><em>Transcript was AI-generated and edited for clarity. </em></strong></p><p class="pb-2"></p></div></div><div class="flex items-center lg:w-3/4 mb-4 pb-12"></div><div class="jsx-19ede9f0a5a45918 py-4 relative bg-primary md:px-8 -ml-6 xs:ml-0 w-screen xs:w-auto"><div class="jsx-19ede9f0a5a45918 px-4 sm:px-0"><div class="flex justify-between items-center py-1 space-x-4 border-0 select-none sm:border-b border-secondary"><div class="text-3xl text-white text-lg sm:text-3xl">Related Videos</div></div></div><div style="scroll-snap-type:none" class="jsx-19ede9f0a5a45918 flex items-start overflow-x-auto space-x-4 py-4 relative mx-auto w-full pl-4"><a id="" class="w-[200px] h-fit space-y-3 flex-none select-none no-underline" style="scroll-snap-align:center;text-decoration:none" 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Here’s How to Cope. </a></p><div class="jsx-ad50481d5ee26850 authors flex-row wrap gap-[0.2rem]"><a class="jsx-ad50481d5ee26850 text-[#00ADEF] underline text-sm italic" href="/authors/james-phelps-md">James Phelps, MD</a></div><div class="jsx-ad50481d5ee26850 article-summary"><a class="jsx-ad50481d5ee26850" href="/view/differential-diagnosis-of-mixed-states-is-nearly-impossible-heres-how-to-cope?utm_source=www.psychiatrictimes.com&utm_medium=relatedContent"></a></div></div></div><div style="border-bottom:1px solid #CCCCCC" class="jsx-ad50481d5ee26850"></div></div></div></div></div><div class="pb-24"></div></div><script type="application/ld+json">{"@context":"https://schema.org","@type":"NewsArticle","headline":"Navigating Major Depressive Disorder (MDD): The Role of Glutamate","datePublished":"2023-11-29T19:08:18.306Z","dateModified":"2023-11-29T19:07:22Z","inLanguage":"en-US","image":"https://cdn.sanity.io/images/0vv8moc6/psychtimes/aaa0626100191147c4489efc055a8b26f4e54a62-1280x720.jpg?fit=crop&auto=format","mainEntityOfPage":{"@type":"WebPage","@id":"https://www.psychiatrictimes.com/view/navigating-major-depressive-disorder-mdd-the-role-of-glutamate"},"publisher":{"@type":"Organization","name":"Psychiatric Times","logo":{"@type":"ImageObject","url":"https://www.psychiatrictimes.com/PsychiatricTimesLogo.png"}},"keywords":"Rapid-acting therapies ,Major Depressive Disorder, Glutamate distribution ,Stress impact ,Personalized mental health","articleBody":"\n\n\n\nTranscript\n\nGus Alva, MD, DFAPA: Welcome to this Psychiatric Times presentation titled, “Bridging the Gap in Major Depressive Disorder Care: Rapid-Acting Therapies and Glutamine. I’m Gus Alva. I’m the founder and medical director of ATP Clinical Research in Orange County, California. I am thrilled to be joined today by Craig Chepke, a board-certified psychiatrist at Excel Psychiatric Associates in Huntersville, North Carolina. We’ve got Greg Mattingly, a physician and principal investigator in clinical trials for Midwest Research Group in St. Charles, Missouri. Last but not least, Erin Crown, a certified physician assistant and managing member at Oasis LifeCare in State College, Pennsylvania. In today’s discussion, we will focus on the role of rapid-acting therapies, specifically NMDA receptor modulators, in the management of major depressive disorder. Our conversation will explore the mechanisms that distinguish rapid-acting treatments from traditional antidepressants and major depressive disorder management and foster a better understanding of treatment-resistant depression, and strategies for addressing it. Lastly, we will examine real patient cases, emphasizing the importance of considering individual patient experiences and tailoring care accordingly. Let’s begin. If we consider the fact that glutamate and its presence in the brain is heavily concentrated in different regions like the cortex, cerebellum, hippocampal region, thalamic nuclei, caudate nucleus, which one of you wants to lead off by telling us why it is that glutamate is where it is in the brain? Why does that matter?\n\n\n\nGreg Mattingly, MD: Glutamate’s the main excitatory chemical in the brain. For neural networks to turn on, glutamate pretty much has to fire. And, Craig, I think it’s like 98% of our synapses are modified by glutamate neurotransmission. The analogy I use quite a bit is it’s kind of like the gas pedal in your car. You can turn on the key, but if the gas pedal doesn’t go, you’re not going to get where you need to be. Glutamate turns on those neural networks and helps them to fire.\n\n\n\nGus Alva, MD, DFAPA: Interesting.\n\n\n\nCraig Chepke, MD, DFAPA: To say where glutamate is in the brain, it’s everywhere. I mean, the whole cortex runs off of glutamate. It’s a glutamate machine, basically. That’s what does the work of the brain.\n\n\n\nGus Alva, MD, DFAPA: Erin, your thoughts on that?\n\n\n\nErin Crown, MHS, PA-C: A little bit of a different direction. It’s heavily influenced by stress, and we know that we all have a lot of stress in our lives in various ways, and it’s impacted by that. So, bottom line: It’s everywhere and highly impacted by stress and inflammation.\n\n\n\nGreg Mattingly, MD: Erin said something that’s fascinating, and this is why I went into psychiatry over 30 years ago. Glutamate starts that whole cascade of neural plasticity. So it’s a key component of turning on neural networks, but not just turning on your neural networks, but turning on the ability to survive under stress. Without that, our brain isn’t plastic. It doesn’t grow. It doesn’t sprout. It doesn’t connect with each other. So we’re turning on neural networks. We’re turning on neural plasticity. We’re allowing nerve cells to reach out and grow and connect with each other, especially in times of stress.\n\n\n\nTranscript was AI-generated and edited for clarity. \n\n","description":"Experts discuss the significance of glutamate in major depressive disorder, highlighting its links to neuroplasticity and stress.","author":[{"@type":"Person","name":"Gustavo Alva, MD, DFAPA"},{"@type":"Person","name":"Craig Chepke, MD, DFAPA, FAPA"},{"@type":"Person","name":"Greg Mattingly, MD"},{"@type":"Person","name":"Erin Crown, MHS, PA-C"}]}</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" 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I’m Gus Alva. I’m the founder and medical director of ATP Clinical Research in Orange County, California. I am thrilled to be joined today by Craig Chepke, a board-certified psychiatrist at Excel Psychiatric Associates in Huntersville, North Carolina. We’ve got Greg Mattingly, a physician and principal investigator in clinical trials for Midwest Research Group in St. Charles, Missouri. Last but not least, Erin Crown, a certified physician assistant and managing member at Oasis LifeCare in State College, Pennsylvania. In today’s discussion, we will focus on the role of rapid-acting therapies, specifically NMDA receptor modulators, in the management of major depressive disorder. Our conversation will explore the mechanisms that distinguish rapid-acting treatments from traditional antidepressants and major depressive disorder management and foster a better understanding of treatment-resistant depression, and strategies for addressing it. Lastly, we will examine real patient cases, emphasizing the importance of considering individual patient experiences and tailoring care accordingly. Let’s begin. If we consider the fact that glutamate and its presence in the brain is heavily concentrated in different regions like the cortex, cerebellum, hippocampal region, thalamic nuclei, caudate nucleus, which one of you wants to lead off by telling us why it is that glutamate is where it is in the brain? Why does that matter?","_key":"64c8c520fb743","_type":"span","marks":[]}],"_type":"block","style":"normal","_key":"57dd89752a64","upload_doc":null,"uploadAudio":null},{"style":"normal","_key":"9b661c8cb565","markDefs":[],"upload_doc":null,"uploadAudio":null,"medias":null,"children":[{"marks":[],"text":"","_key":"1eeaad8df5ea0","_type":"span"}],"_type":"block"},{"children":[{"_key":"8774f3d5519d0","_type":"span","marks":["strong"],"text":"Greg Mattingly, MD:"},{"_type":"span","marks":[],"text":" Glutamate’s the main excitatory chemical in the brain. For neural networks to turn on, glutamate pretty much has to fire. And, Craig, I think it’s like 98% of our synapses are modified by glutamate neurotransmission. The analogy I use quite a bit is it’s kind of like the gas pedal in your car. You can turn on the key, but if the gas pedal doesn’t go, you’re not going to get where you need to be. Glutamate turns on those neural networks and helps them to fire.","_key":"8774f3d5519d1"}],"_type":"block","style":"normal","_key":"36c75ad75b9a","upload_doc":null,"uploadAudio":null,"medias":null,"markDefs":[]},{"medias":null,"markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"033e73e094d90"}],"_type":"block","style":"normal","_key":"252f6f5acc84","upload_doc":null,"uploadAudio":null},{"uploadAudio":null,"medias":null,"markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Gus Alva, MD, DFAPA:","_key":"362c689899310"},{"_type":"span","marks":[],"text":" Interesting.","_key":"362c689899311"}],"_type":"block","style":"normal","_key":"f597ea9dc19f","upload_doc":null},{"_key":"af0d2aff499a","markDefs":[],"children":[{"marks":[],"text":"","_key":"f3c1247266370","_type":"span"}],"_type":"block","style":"normal","upload_doc":null,"uploadAudio":null,"medias":null},{"uploadAudio":null,"medias":null,"_type":"block","style":"normal","_key":"1d59998a1646","markDefs":[],"children":[{"text":"Craig Chepke, MD, DFAPA:","_key":"e3bf224427c80","_type":"span","marks":["strong"]},{"text":" To say where glutamate is in the brain, it’s everywhere. I mean, the whole cortex runs off of glutamate. It’s a glutamate machine, basically. That’s what does the work of the brain.","_key":"e3bf224427c81","_type":"span","marks":[]}],"upload_doc":null},{"style":"normal","upload_doc":null,"uploadAudio":null,"medias":null,"_key":"31e22d5163c9","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"5b0329ebc8100"}],"_type":"block"},{"medias":null,"_key":"a39141ff621f","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Gus Alva, MD, DFAPA:","_key":"b5cc757c99ec0"},{"_type":"span","marks":[],"text":" Erin, your thoughts on that?","_key":"b5cc757c99ec1"}],"_type":"block","style":"normal","upload_doc":null,"uploadAudio":null},{"_type":"block","style":"normal","upload_doc":null,"uploadAudio":null,"medias":null,"_key":"5f949aab8193","markDefs":[],"children":[{"marks":[],"text":"","_key":"42f19919947d0","_type":"span"}]},{"_key":"872f0b42bad6","markDefs":[],"children":[{"marks":["strong"],"text":"Erin Crown, MHS, PA-C:","_key":"116ce1c251600","_type":"span"},{"_type":"span","marks":[],"text":" A little bit of a different direction. It’s heavily influenced by stress, and we know that we all have a lot of stress in our lives in various ways, and it’s impacted by that. So, bottom line: It’s everywhere and highly impacted by stress and inflammation.","_key":"116ce1c251601"}],"_type":"block","upload_doc":null,"uploadAudio":null,"medias":null,"style":"normal"},{"_key":"13c287a78603","markDefs":[],"children":[{"text":"","_key":"8afe2e0a1d550","_type":"span","marks":[]}],"_type":"block","upload_doc":null,"uploadAudio":null,"medias":null,"style":"normal"},{"upload_doc":null,"uploadAudio":null,"medias":null,"style":"normal","_key":"2f012e540eb2","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Greg Mattingly, MD:","_key":"9bc2f4cd61190"},{"_type":"span","marks":[],"text":" Erin said something that’s fascinating, and this is why I went into psychiatry over 30 years ago. Glutamate starts that whole cascade of neural plasticity. So it’s a key component of turning on neural networks, but not just turning on your neural networks, but turning on the ability to survive under stress. Without that, our brain isn’t plastic. It doesn’t grow. It doesn’t sprout. It doesn’t connect with each other. So we’re turning on neural networks. We’re turning on neural plasticity. We’re allowing nerve cells to reach out and grow and connect with each other, especially in times of stress.","_key":"9bc2f4cd61191"}],"_type":"block"},{"_type":"block","style":"normal","_key":"19653284ec4e","upload_doc":null,"uploadAudio":null,"medias":null,"markDefs":[],"children":[{"text":"","_key":"5f5805ed3600","_type":"span","marks":[]}]},{"upload_doc":null,"uploadAudio":null,"medias":null,"children":[{"_type":"span","marks":["strong","em"],"text":"Transcript was AI-generated and edited for clarity. 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Patients were also excluded if they self-reported a history of epilepsy, experienced uncontrollable physical illness, developed a physical illness during the study, decided to discontinue ECT, or refused to sign the informed consent form.","_key":"e7e45bc0393b0"}],"_type":"block","style":"normal","_key":"57c6c2f7c5a6"},{"style":"normal","_key":"8f01c3fabfb3","markDefs":[],"children":[{"_type":"span","marks":[],"text":"A control group of 29 participants was gathered based on matching patient age, gender, and educational attainment. The control group reported no lifetime mental disorders among immediate family or a family history of psychiatric conditions.","_key":"55c4b5c5bba30"}],"_type":"block"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"Blood samples were taken at the beginning and end of the study to measure inflammatory markers (IL-1β, IL-6, IL-10). ECT was administered between 8 AM and 12 PM using the Thymatron DGx system, placing electrodes bilaterally on the temples. A low pulse width setting of 0.25 and a current of 0.9A was administered, with the initial energy adjusted to 50% of the participant’s age. Propofol (1.5-2 mg/kg) and succinylcholine (0.5-1 mg/ kg) were administered for anesthesia and muscle relaxation.","_key":"d7fefc2226150"}],"_type":"block","style":"normal","_key":"cd4690d2f472"},{"style":"normal","_key":"a2a6005935eb","markDefs":[],"children":[{"_type":"span","marks":[],"text":"The treatment lasted 2 weeks, starting patients with 3 to 4 days of daily treatment, then transitioning to treatments on alternating days with a 2-day break on weekends.","_key":"1c4fa27530cd0"}],"_type":"block"},{"_type":"block","style":"normal","_key":"3c6dd4a0be29","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"3b937488722b"}]},{"markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Results","_key":"17f39bb6e2830"}],"_type":"block","style":"normal","_key":"adc9df297356"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"Researchers found that after ECT, pro-inflammatory cytokines decreased significantly and anti-inflammatory cytokines increased. HAMD-17 scores of 63% of patients were reported as having decreased by 505b or more, classifying them as responders to treatment. The research shows responders exhibited greater reductions of IL-1β and IL-6 and higher IL-10 increases compared to patients considered nonresponders.","_key":"6f70c7d608560"}],"_type":"block","style":"normal","_key":"7dbe5a6f9bdf"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"“The mitigation of depressive symptoms exhibited a moderate correlation with post-treatments decrements in IL-1β and IL-6 levels, underscoring MDD’s intricacy and ECT’s comprehensive impact,”","_key":"06b67f33ec910"},{"_key":"61dee85ecfea","_type":"span","marks":["superscript"],"text":"2 "},{"marks":[],"text":"authors of the study concluded. Although initial cytokine levels did not predict response to ECT, posttreatment decreases in IL-1β and IL-6 could be used to predict clinical improvement.","_key":"bfdc5a44a891","_type":"span"}],"_type":"block","style":"normal","_key":"e526d79eceda"},{"style":"normal","_key":"1d179adcdfbc","markDefs":[],"children":[{"_type":"span","marks":[],"text":"The research suggests inflammation may be considered in part when treating MDD, particularly when treatment involves ECT. Elevated inflammatory markers in patients before beginning treatment may indicate a higher immune response activated by depression. 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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."}],"_type":"block","style":"normal","_key":"069af0e50d8d","markDefs":[]},{"_type":"block","style":"normal","_key":"7641e7f4c6d3","markDefs":[{"_key":"fe0f92d0923b","blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/32252567/"}],"children":[{"_type":"span","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. 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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":["strong"],"text":" ","_key":"285651f59c0a"},{"_type":"span","marks":[],"text":"Another option is lowbluelights.com.","_key":"46a5e7d06801"},{"_type":"span","marks":["strong"],"text":" ","_key":"11eb94fabb93"},{"_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"}]},{"_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","style":"normal"},{"_type":"block","style":"normal","_key":"59a191d00673","markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/15713707/","_key":"12575d5be836"}],"children":[{"_type":"span","marks":["strong"],"text":"CHRIS AIKEN","_key":"1a20ca278b3c0"},{"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":[]},{"marks":["12575d5be836"],"text":"pitch-dark room","_key":"390d3a981cbc","_type":"span"},{"_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"},{"marks":["superscript"],"text":"5","_key":"2599727d60a1","_type":"span"},{"_key":"555373281736","_type":"span","marks":[],"text":" So it’s not enough to have melatonin drizzled on the brain. 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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. 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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 ","_key":"248c11caaf5c1","_type":"span"},{"_type":"span","marks":["0ed721ba65fa"],"text":"born","_key":"7b881f4d97bb"},{"_type":"span","marks":[],"text":".","_key":"acda32c28c17"},{"marks":["superscript"],"text":"7","_key":"29d23936e285","_type":"span"}],"_type":"block","style":"normal","_key":"4e8d605914a3"},{"_key":"52ef0cf3e93f","markDefs":[],"children":[{"marks":["strong"],"text":"KN","_key":"28fdb6c254e70","_type":"span"},{"_key":"28fdb6c254e71","_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."}],"_type":"block","style":"normal"},{"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"},{"_type":"span","marks":["superscript"],"text":"8","_key":"065994221bfc"}],"_type":"block","style":"normal","_key":"78971994f42f"},{"_type":"block","style":"normal","_key":"390955093fb9","markDefs":[],"children":[{"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"},{"_key":"186d9f90286e","_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."}]},{"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"},{"text":"2","_key":"8839f67a375e","_type":"span","marks":["superscript"]}],"_type":"block"},{"style":"normal","_key":"cc6b6fdc0b3d","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"The Protocol","_key":"1394ceb614ae0"}],"_type":"block"},{"_key":"596761a4cde7","markDefs":[],"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"},{"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","style":"normal","_key":"0c4add95764a"},{"style":"normal","_key":"c3741b08e60d","markDefs":[],"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"},{"_type":"block","style":"normal","_key":"97b2fbfacdec","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"}]},{"markDefs":[],"children":[{"text":"CA","_key":"d49119795ed50","_type":"span","marks":["strong"]},{"_type":"span","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":"block","style":"normal","_key":"8273b2575cc1"},{"markDefs":[],"children":[{"marks":["strong"],"text":"KN","_key":"350baa9963580","_type":"span"},{"_type":"span","marks":[],"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":"block","style":"normal","_key":"be6037e19876"},{"markDefs":[],"children":[{"_type":"span","marks":[],"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":"block","style":"normal","_key":"4686c1580b2e"},{"style":"normal","_key":"e7257a6d8b9d","markDefs":[],"children":[{"marks":["strong"],"text":"CA","_key":"08f2c9b1d95b0","_type":"span"},{"_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"},{"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","_type":"span"}],"_type":"block"},{"_type":"block","style":"normal","_key":"b5c98c8d3194","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Dark Therapy for Insomnia","_key":"48c1d1ea6fac0"}]},{"_type":"block","style":"normal","_key":"e5c617dea0f8","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"KN","_key":"c513a824ead30"},{"_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"},{"_type":"span","marks":["superscript"],"text":"10-12","_key":"8e57359618ec"},{"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","_type":"span"},{"_type":"span","marks":["superscript"],"text":"11","_key":"0f8658398107"},{"_type":"span","marks":[],"text":" In the sleep studies, patients put the glasses on 1.5 to 2 hours before bedtime.","_key":"98a0034680a3"}]},{"markDefs":[],"children":[{"text":"Blue light blockers have been used successfully in jet lag, and they tend to help night owls fall asleep earlier.","_key":"fa05ef5e016d0","_type":"span","marks":[]}],"_type":"block","style":"normal","_key":"c7b0aabbd537"},{"_type":"block","style":"normal","_key":"5bbc20f2c723","markDefs":[],"children":[{"marks":["strong"],"text":"CA","_key":"08b9b8d0af4d0","_type":"span"},{"_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":[{"text":"Dark Therapy for Depression","_key":"e1c47995de9a0","_type":"span","marks":["strong"]}]},{"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"},{"marks":["superscript"],"text":"10","_key":"a07fecd7c3f5","_type":"span"},{"_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"},{"_key":"b361669caef5","_type":"span","marks":["superscript"],"text":"13"},{"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"},{"_type":"span","marks":["superscript"],"text":"14","_key":"489c274fec81"}],"_type":"block","style":"normal","_key":"d00277c9dd9f"},{"markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Warnings","_key":"8ef4c38d11c10"}],"_type":"block","style":"normal","_key":"95648ec7ee55"},{"_key":"0a03b0a2d077","markDefs":[],"children":[{"marks":["strong"],"text":"CA","_key":"e8037cb641160","_type":"span"},{"_key":"e8037cb641161","_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. Although you can see pretty clearly through the glasses, color vision is distorted so we don’t recommend them while driving."}],"_type":"block","style":"normal"},{"markDefs":[],"children":[{"marks":["strong"],"text":"KELLIE NEWSOME","_key":"8eabe01ecb250","_type":"span"},{"_type":"span","marks":[],"text":": We have links to recommended brands of blue-light blockers in the text to this podcast. 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","_key":"080d896164030"},{"_type":"span","marks":["9ffb957f4ad0"],"text":"Nocturnal light exposure impairs affective responses in a wavelength-dependent manner.","_key":"080d896164031"},{"_key":"080d896164032","_type":"span","marks":[],"text":" "},{"_type":"span","marks":["em"],"text":"J Neurosci. ","_key":"080d896164033"},{"_key":"080d896164034","_type":"span","marks":[],"text":"2013;33(32):13081-13087."}],"_type":"block","style":"normal","_key":"fa2d733e1e09","markDefs":[{"_type":"link","href":"https://www.ncbi.nlm.nih.gov/pubmed/23926261","_key":"9ffb957f4ad0"}]},{"markDefs":[{"_type":"link","href":"https://www.ncbi.nlm.nih.gov/pubmed/27226262","_key":"45124289dcea"}],"children":[{"_type":"span","marks":[],"text":"2. Henriksen TE, Skrede S, Fasmer OB, et al. ","_key":"f690684f295a0"},{"_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"},{"marks":[],"text":". 2016;18(3):221-232.","_key":"f690684f295a4","_type":"span"}],"_type":"block","style":"normal","_key":"b97351169646"},{"markDefs":[{"_key":"3884d6ee42b8","_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/32252567/"}],"children":[{"_type":"span","marks":[],"text":"3. Wang RR, Hao Y, Guo H, et al. ","_key":"9bd0c1b6373b0"},{"_key":"9bd0c1b6373b1","_type":"span","marks":["3884d6ee42b8"],"text":"Lunar cycle and psychiatric hospital admissions for schizophrenia: new findings from Henan province, China."},{"_type":"span","marks":[],"text":" ","_key":"9bd0c1b6373b2"},{"marks":["em"],"text":"Chronobiol Int","_key":"9bd0c1b6373b3","_type":"span"},{"_type":"span","marks":[],"text":". 2020;37(3):438-449.","_key":"9bd0c1b6373b4"}],"_type":"block","style":"normal","_key":"0998fad1e801"},{"_key":"5cb7b6d5d358","markDefs":[{"_key":"56e546bfed16","_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/15713707/"}],"children":[{"_key":"5c883b154b8e0","_type":"span","marks":[],"text":"4. Kayumov L, Casper RF, Hawa RJ, et al. "},{"_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"},{"marks":[],"text":" ","_key":"5c883b154b8e2","_type":"span"},{"_type":"span","marks":["em"],"text":"J Clin Endocrinol Metab","_key":"5c883b154b8e3"},{"text":". 2005;90(5):2755-2761.","_key":"5c883b154b8e4","_type":"span","marks":[]}],"_type":"block","style":"normal"},{"style":"normal","_key":"ace75fc73a52","markDefs":[{"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/32474993/","_key":"661b6401c265"}],"children":[{"_type":"span","marks":[],"text":"5. Quested DJ, Gibson JC, Sharpley AL, et al. Melatonin In Acute Mania Investigation (MIAMI-UK). ","_key":"e625229b6ed90"},{"_type":"span","marks":["661b6401c265"],"text":"A randomized controlled trial of add-on melatonin in bipolar disorder.","_key":"e625229b6ed91"},{"marks":[],"text":" ","_key":"e625229b6ed92","_type":"span"},{"marks":["em"],"text":"Bipolar Disord","_key":"e625229b6ed93","_type":"span"},{"_type":"span","marks":[],"text":". 2021;23(2):176-185.","_key":"e625229b6ed94"}],"_type":"block"},{"markDefs":[{"_key":"d792a216f0c0","_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/7512910/"}],"children":[{"marks":[],"text":"6. Barbato G, Barker C, Bender C, et al. ","_key":"94ff1ad30bae0","_type":"span"},{"_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"},{"text":" ","_key":"94ff1ad30bae2","_type":"span","marks":[]},{"marks":["em"],"text":"Electroencephalogr Clin Neurophysiol","_key":"94ff1ad30bae3","_type":"span"},{"marks":[],"text":". 1994;90(4):291-297.","_key":"94ff1ad30bae4","_type":"span"}],"_type":"block","style":"normal","_key":"a2db7ccafcdf"},{"children":[{"text":"7. Wehr TA, Turner EH, Shimada JM, et al. ","_key":"f8285e4742170","_type":"span","marks":[]},{"_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.","_key":"f8285e4742171"},{"_key":"f8285e4742172","_type":"span","marks":[],"text":" "},{"text":"Biol Psychiatry","_key":"f8285e4742173","_type":"span","marks":["em"]},{"_type":"span","marks":[],"text":". 1998;43(11):822-828.","_key":"f8285e4742174"}],"_type":"block","style":"normal","_key":"f3ff2e13b6ea","markDefs":[{"_key":"a8d7ad388575","_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/9611672/"}]},{"_type":"block","style":"normal","_key":"c9d938860932","markDefs":[{"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/17637502/","_key":"b6de4ee3a9d5"}],"children":[{"_key":"15cd6439011c0","_type":"span","marks":[],"text":"8. Phelps J. 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With these symptoms, bipolar mixed states overlap almost completely with those of ","_key":"4e5ff86c7daf0"},{"_key":"67ebf2a933fc","_type":"span","marks":["1ea498eb1a16"],"text":"posttraumatic stress disorder"},{"_type":"span","marks":[],"text":" (PTSD) with depression, generalized anxiety disorder (GAD) with depression, attention deficit disorder (ADD) with depression, and ","_key":"e2ed83948b3e"},{"_type":"span","marks":["6364a9ec098f"],"text":"borderline personality disorder","_key":"329ff50803c8"},{"_type":"span","marks":[],"text":".","_key":"2f62088f407c"}],"_type":"block","style":"normal","_key":"14a384419cc7","markDefs":[{"nofollow":true,"blank":true,"_type":"link","href":"https://www.psychiatrictimes.com/topics/ptsd","_key":"1ea498eb1a16"},{"blank":true,"_type":"link","href":"https://www.psychiatrictimes.com/topics/personality-disorders","_key":"6364a9ec098f","nofollow":true}]},{"_key":"a579010d1481","markDefs":[],"children":[{"marks":[],"text":"","_key":"7a378520683c0","_type":"span"}],"_type":"block","style":"normal"},{"_type":"block","style":"normal","_key":"409bec3037da","markDefs":[],"children":[{"_type":"span","marks":[],"text":"This essay presents 4 means of coping with the diagnostic uncertainty that results from this overlap.","_key":"f35dc399e7a80"}]},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"f8b63e5eab280"}],"_type":"block","style":"normal","_key":"08be638e487c"},{"children":[{"_type":"span","marks":["strong"],"text":"1. 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No diagnosis should be proffered until they are obtained and evaluated.","_key":"06da9a469a8d0"}],"_type":"block","style":"normal","_key":"4ec84dbf939c"},{"markDefs":[],"children":[{"text":"","_key":"a35b7b0349e60","_type":"span","marks":[]}],"_type":"block","style":"normal","_key":"7e8f74f43677"},{"_key":"424ec05c9df6","markDefs":[{"blank":true,"_type":"link","href":"https://www.psychiatrictimes.com/view/efficient-assessment-20-questions-about-bipolarity-moodcheck","_key":"1d4afd973797"}],"children":[{"_type":"span","marks":[],"text":"But the sheer volume of information one is expected to gather in an initial interview can interfere with establishing trust and rapport through open-ended questions and accurate reflective listening. Using questionnaires to gather some of this information is efficient but can be cumbersome: how much can you ask a patient to divulge before meeting you in person? For a short questionnaire designed to capture mood symptoms ","_key":"3d648a40293e0"},{"_key":"3d648a40293e1","_type":"span","marks":["em"],"text":"and"},{"_type":"span","marks":[],"text":" family history, age of onset, illness course, and response to antidepressants, consider “MoodCheck”, described in ","_key":"3d648a40293e2"},{"_type":"span","marks":["em"],"text":"Psychiatric Times","_key":"3d648a40293e3"},{"_type":"span","marks":[],"text":" in ","_key":"3d648a40293e4"},{"_type":"span","marks":["1d4afd973797"],"text":"2017","_key":"3d648a40293e5"},{"_type":"span","marks":[],"text":" and available for direct download (no profit or industry connections).","_key":"3d648a40293e6"},{"_type":"span","marks":["superscript"],"text":"3","_key":"fb27cc7d34d6"}],"_type":"block","style":"normal"},{"_type":"block","style":"normal","_key":"c6bfafb49464","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"24f6d130b6200"}]},{"markDefs":[],"children":[{"marks":["strong"],"text":"2. Recruit the Patient (And Perhaps Family)","_key":"4193a52422500","_type":"span"}],"_type":"block","style":"normal","_key":"e5f882a4b647"},{"_key":"9c1deae87048","markDefs":[],"children":[{"_type":"span","marks":[],"text":"Shared decision-making involves more than simply explaining treatment pros and cons. It includes understanding the patient’s beliefs and fears and social milieu. For example, is PTSD a preferred diagnosis because it places causality outside the patient? Is ADD preferred because it is a simple explanation for struggling in school? How much stigma is attached to the word bipolar, in the patient’s mind, and their family’s, and their community?","_key":"ee2c5548804d0"}],"_type":"block","style":"normal"},{"style":"normal","_key":"04848dcbb3b0","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"d44a0069a4170"}],"_type":"block"},{"style":"normal","_key":"08d4d5af8095","markDefs":[],"children":[{"marks":[],"text":"With these insights in hand or in development, a good clinician helps the patient (and perhaps family) understand the diagnostic challenge of mixed states. One might say “There are a couple of ways to explain your symptoms. No single diagnosis is obvious. We have to consider several” (enumerating those most likely, including bipolar without mania). Another variation: “You do not have bipolar disorder, but you do not have plain depression either. You may be somewhere in between.”","_key":"ffb23894da5a0","_type":"span"}],"_type":"block"},{"children":[{"text":"","_key":"e364a4bc28500","_type":"span","marks":[]}],"_type":"block","style":"normal","_key":"3f9b3c10f471","markDefs":[]},{"_type":"block","style":"normal","_key":"b9ae5a9e4f8c","markDefs":[],"children":[{"_type":"span","marks":[],"text":"When time is limited, especially in an initial interview, it is almost impossible to be this deliberate explaining a complex differential. But many patients, if they leave with limited information, will turn to the internet. Unguided searching can easily lead to misimpressions. You could create your own website, or a handout of recommended sites to direct your patients’ searches. For that list, consider a site built recently for patients with depression that emphasizes all the themes in the essay you are reading now (no profit, no advertising).","_key":"bd5f7bd5e02f0"},{"_type":"span","marks":["superscript"],"text":"4","_key":"16497d1efc3e"}]},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"01062a9426d70"}],"_type":"block","style":"normal","_key":"3c1600dc27b5"},{"children":[{"marks":["strong"],"text":"3. 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Psychotherapies have lower risks than medications, even if targeting the “wrong” diagnosis; indeed, several are likely to help even when misdirected.","_key":"1ac8ffc40373"}],"_type":"block","style":"normal"},{"children":[{"marks":[],"text":"","_key":"a8990d1b4beb0","_type":"span"}],"_type":"block","style":"normal","_key":"1a57a9fa4813","markDefs":[]},{"_key":"9c7e13d94e00","markDefs":[],"children":[{"_type":"span","marks":[],"text":"In the face of diagnostic uncertainty, you can offer or refer the patient to a psychotherapy specific for the most likely diagnosis, or therapy likely to benefit any of several diagnostic possibilities. For example, some therapies are PTSD-specific, focusing on trauma, while basic cognitive-behavioral therapy (CBT) may still be of benefit in PTSD through components such as stress management and mindfulness skills. Similarly, CBT is likely to help a patient whose depression is mixed, or even bipolar II depression. A meta-analysis of 409 trials found CBT equally effective as medications for depression in the short term, and better in the long term.","_key":"627ba31e9a3a0"},{"text":"5","_key":"d38313e2c465","_type":"span","marks":["superscript"]}],"_type":"block","style":"normal"},{"_key":"f9396c3b2c78","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"aa3bb1c3ab200"}],"_type":"block","style":"normal"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"Unfortunately, unless you have a solid referral network, it can be difficult to confidently refer patients for psychotherapy. The best local therapists are often not routinely taking new patients. For online therapy, some websites allow a patient to choose a particular kind of therapy, but you cannot control the quality.","_key":"69922eaa370b0"}],"_type":"block","style":"normal","_key":"4c21870797ce"},{"_key":"f8599a3ed871","markDefs":[],"children":[{"_key":"46b370ff497e0","_type":"span","marks":[],"text":""}],"_type":"block","style":"normal"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"Digital therapeutics (DTX) include websites and apps that provide a kind of psychotherapy. Web-based versions of CBT have been shown to be nearly as effective as a live therapist, particularly if guided with some minimal support.","_key":"ae7378618d4e0"},{"text":"6","_key":"af6584f9cf3c","_type":"span","marks":["superscript"]},{"marks":[],"text":" Online therapies for PTSD also have shown efficacy, although patients are more likely to drop out if the intervention focuses on stabilization (as do the majority of such programs) when they are looking for trauma-focused work.","_key":"b5daf72142f6","_type":"span"},{"_type":"span","marks":["superscript"],"text":"7","_key":"57dc2804b8da"}],"_type":"block","style":"normal","_key":"c3ad4a1af5f9"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"c750da621e810"}],"_type":"block","style":"normal","_key":"e6ed0303cf28"},{"markDefs":[],"children":[{"marks":[],"text":"Some of the best studied versions of online CBT rely on patient motivation to work through the modules.","_key":"6e1078fed0820","_type":"span"},{"marks":["superscript"],"text":"8","_key":"7a43e9df9599","_type":"span"},{"_type":"span","marks":[],"text":" Completion rates have been as low as 10% in some of these studies.","_key":"0d6304d98299"},{"_type":"span","marks":["superscript"],"text":"9","_key":"0597a5194280"},{"_type":"span","marks":[],"text":" By contrast, newer DTX programs “push” adherence with programmed messages and limited text-based support. With these, 1 industry-sponsored study demonstrated almost 90% adherence after 12 of 16 sessions.","_key":"fe48900dd3f1"},{"_key":"e95681bcae79","_type":"span","marks":["superscript"],"text":"10"}],"_type":"block","style":"normal","_key":"c2840482743d"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"ee4b5841248b0"}],"_type":"block","style":"normal","_key":"07943f40613a"},{"style":"normal","_key":"a8cd0a74de9d","markDefs":[],"children":[{"_type":"span","marks":[],"text":"In that industry-sponsored study, the absolute difference in the primary outcome measure (MADRS) vs an active control condition was small. But all patients were already on an antidepressant and the control was a very plausible version of the treatment app, perhaps limiting improvement and separation. Data from further research will be of great interest. In the meantime, it appears that the push technology represents a major advance vs older DTXs.","_key":"beaeefab38d60"}],"_type":"block"},{"_key":"7152a1da38ba","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"679b26ba5e450"}],"_type":"block","style":"normal"},{"markDefs":[],"children":[{"text":"As a final reason to more deeply consider adding DTX to your toolkit, note that Medicare and Medicaid Services have proposed new CPT codes that would pay for prescribing and managing these tools. (In an important twist, only “FDA-approved” programs would be allowed, thus excluding several existing programs that have not sought such approval). Code GMBT1 would allow clinicians to bill for giving DTX to patients and teaching them how to use it. The idea is to make DTX rather like giving a vaccine. Code GMBT2 covers the first 20 minutes of “monthly management services,” such as reviewing the data from the DTX device.","_key":"8f248968726f0","_type":"span","marks":[]},{"marks":["superscript"],"text":"11","_key":"de7dab8a8bfb","_type":"span"}],"_type":"block","style":"normal","_key":"c496c3cbbf2f"},{"children":[{"marks":[],"text":"","_key":"5fa46fc4153c0","_type":"span"}],"_type":"block","style":"normal","_key":"3305fa1be214","markDefs":[]},{"markDefs":[],"children":[{"marks":["strong"],"text":"4. Compare Treatment Risks","_key":"2fb32e6222360","_type":"span"}],"_type":"block","style":"normal","_key":"1a9e9ab3e57a"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"If beginning with a medication treatment rather than a psychotherapy, a fourth means of coping with diagnostic uncertainty is to help the patient compare the risks of treatment options associated with possible diagnoses. This approach is detailed in Part 3 of this series.","_key":"709ecdf704770"}],"_type":"block","style":"normal","_key":"0e1e0631dfde"},{"children":[{"_type":"span","marks":[],"text":"","_key":"50f0439333cd0"}],"_type":"block","style":"normal","_key":"340b73a3e070","markDefs":[]},{"markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Concluding Thoughts","_key":"6029913f51c40"}],"_type":"block","style":"normal","_key":"ec6f1eb38e1b"},{"markDefs":[],"children":[{"_key":"e692eaca9ba70","_type":"span","marks":[],"text":"Because of overlapping symptoms, distinguishing mixed states from other common presentations of depression can be nearly impossible. This essay describes 4 means of coping with that uncertainty, including respective clinical tools: "},{"_type":"span","marks":["em"],"text":"gathering data","_key":"e692eaca9ba71"},{"_type":"span","marks":[],"text":" using a broad but brief questionnaire; ","_key":"e692eaca9ba72"},{"_type":"span","marks":["em"],"text":"patient education","_key":"e692eaca9ba73"},{"marks":[],"text":", augmented with reliable internet sources; starting with a ","_key":"e692eaca9ba74","_type":"span"},{"text":"psychotherapy","_key":"e692eaca9ba75","_type":"span","marks":["em"]},{"_type":"span","marks":[],"text":", including DTX; and patient education ","_key":"e692eaca9ba76"},{"_type":"span","marks":["em"],"text":"comparing treatment risks","_key":"e692eaca9ba77"},{"_key":"e692eaca9ba78","_type":"span","marks":[],"text":"."}],"_type":"block","style":"normal","_key":"bceb3730b6f6"},{"style":"normal","_key":"52e6fed7438a","markDefs":[],"children":[{"marks":[],"text":"","_key":"56939e5608990","_type":"span"}],"_type":"block"},{"markDefs":[{"blank":true,"_type":"link","href":"https://wwnorton.com/books/A-Spectrum-Approach-to-Mood-Disorders/","_key":"ca2683fb96a4"},{"blank":true,"_type":"link","href":"https://wwnorton.com/books/Bipolar-Not-So-Much/","_key":"c778ff5bea03"}],"children":[{"_type":"span","marks":["strong"],"text":"Dr Phelps","_key":"ec89bee9541f0"},{"_type":"span","marks":[],"text":" ","_key":"ec89bee9541f1"},{"marks":["em"],"text":"is retiring from 30 years of treating complex mood disorders, and recently founded another website, DepressionEducation.org. 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Mitchell PB, Goodwin GM, Johnson GF, Hirschfeld RM. ","_key":"7a240a9e93da0"},{"_type":"span","marks":["c0d37f0aac4a"],"text":"Diagnostic guidelines for bipolar depression: a probabilistic approach.","_key":"7a240a9e93da1"},{"_type":"span","marks":[],"text":" ","_key":"bda32fe24155"},{"_type":"span","marks":["em"],"text":"Bipolar Disord","_key":"7a240a9e93da2"},{"_key":"7a240a9e93da3","_type":"span","marks":[],"text":". 2008;10(1 pt 2):144-152."}],"_type":"block","style":"normal","_key":"3ba195b3cb36"},{"style":"normal","_key":"f63d8051cf0a","markDefs":[{"href":"https://pubmed.ncbi.nlm.nih.gov/18199236/","_key":"b0fb3d72396b","blank":true,"_type":"link"}],"children":[{"_key":"76925323d1ba0","_type":"span","marks":[],"text":"2. Phelps J, Angst J, Katzow J, Sadler J. "},{"_type":"span","marks":["b0fb3d72396b"],"text":"Validity and utility of bipolar spectrum models.","_key":"76925323d1ba1"},{"_key":"76925323d1ba2","_type":"span","marks":["em"],"text":" Bipolar Disord."},{"_type":"span","marks":[],"text":" 2008;10(1 pt 2):179-193.","_key":"76925323d1ba3"}],"_type":"block"},{"children":[{"_type":"span","marks":[],"text":"3. MoodCheck. Depression Education. Accessed November 7, 2024. ","_key":"e3511d2120b90"},{"_type":"span","marks":["fdcdc08bbfc0"],"text":"https://depressioneducation.org/depression-section-page-1/questionnaire-moodcheck/","_key":"e3511d2120b91"}],"_type":"block","style":"normal","_key":"6f1c01ea31cc","markDefs":[{"blank":true,"_type":"link","href":"https://depressioneducation.org/depression-section-page-1/questionnaire-moodcheck/","_key":"fdcdc08bbfc0"}]},{"children":[{"_type":"span","marks":[],"text":"4. Depression Education. Accessed November 7, 2024. ","_key":"107d260e128d0"},{"text":"https://depressioneducation.org/","_key":"107d260e128d1","_type":"span","marks":["8c2129845eb1"]}],"_type":"block","style":"normal","_key":"e3804abe06c5","markDefs":[{"blank":true,"_type":"link","href":"https://depressioneducation.org/","_key":"8c2129845eb1"}]},{"_key":"1fd7d4367ef2","markDefs":[{"_key":"e9e8fd514891","blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/36640411/"}],"children":[{"_type":"span","marks":[],"text":"5. Cuijpers P, Miguel C, Harrer M, et al. ","_key":"a6931add4d130"},{"text":"Cognitive behavior therapy vs. control conditions, other psychotherapies, pharmacotherapies and combined treatment for depression: a comprehensive meta‐analysis including 409 trials with 52,702 patients.","_key":"a6931add4d131","_type":"span","marks":["e9e8fd514891"]},{"_type":"span","marks":[],"text":" ","_key":"c10fb1005472"},{"_type":"span","marks":["em"],"text":"World Psychiatry","_key":"a6931add4d132"},{"_type":"span","marks":[],"text":". 2023;22(1):105-115.","_key":"a6931add4d133"}],"_type":"block","style":"normal"},{"children":[{"_type":"span","marks":[],"text":"6. Karyotaki E, Efthimiou O, Miguel C, et al. ","_key":"c82b577c83010"},{"_type":"span","marks":["d9fde6da4e47"],"text":"Internet-based cognitive behavioral therapy for depression: a systematic review and individual patient data network meta-analysis.","_key":"c82b577c83011"},{"_type":"span","marks":[],"text":" ","_key":"a792071a4748"},{"_type":"span","marks":["em"],"text":"JAMA Psychiatry","_key":"c82b577c83012"},{"_type":"span","marks":[],"text":". 2021;78(4):361-371.","_key":"c82b577c83013"}],"_type":"block","style":"normal","_key":"524017ca8ba9","markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/33471111/","_key":"d9fde6da4e47"}]},{"markDefs":[{"href":"https://pubmed.ncbi.nlm.nih.gov/38533796/","_key":"3c43e2c30b6b","blank":true,"_type":"link"}],"children":[{"_type":"span","marks":[],"text":"7. Blackie M, De Boer K, Seabrook L, et al. ","_key":"fcfa04e73fb20"},{"marks":["3c43e2c30b6b"],"text":"Digital-based interventions for complex post-traumatic stress disorder: a systematic literature review.","_key":"fcfa04e73fb21","_type":"span"},{"_type":"span","marks":[],"text":" ","_key":"41a327581cd3"},{"_type":"span","marks":["em"],"text":"Trauma Violence Abuse.","_key":"fcfa04e73fb22"},{"_type":"span","marks":[],"text":" 2024;25(4):3115-3130.","_key":"fcfa04e73fb23"}],"_type":"block","style":"normal","_key":"ef7ab4584a17"},{"_type":"block","style":"normal","_key":"2d29d5d08fea","markDefs":[{"blank":true,"_type":"link","href":"https://www.moodgym.com.au/","_key":"07de12de1423"}],"children":[{"_type":"span","marks":[],"text":"8. MoodGym. Accessed November 7, 2024. ","_key":"a4e5bf4804460"},{"_key":"a4e5bf4804461","_type":"span","marks":["07de12de1423"],"text":"https://www.moodgym.com.au/"}]},{"children":[{"_type":"span","marks":[],"text":"9. Twomey C, O’Reilly G. ","_key":"807895b3aa170"},{"_key":"807895b3aa171","_type":"span","marks":["b43834a1f2a5"],"text":"Effectiveness of a freely available computerised cognitive behavioural therapy programme (MoodGYM) for depression: meta-analysis."},{"_type":"span","marks":[],"text":" ","_key":"4341916afd64"},{"_type":"span","marks":["em"],"text":"Aust N Z J Psychiatry","_key":"807895b3aa172"},{"_type":"span","marks":[],"text":". 2017;51(3):260-269.","_key":"807895b3aa173"}],"_type":"block","style":"normal","_key":"3e546b3afe8c","markDefs":[{"blank":true,"_type":"link","href":"https://pubmed.ncbi.nlm.nih.gov/27384752/","_key":"b43834a1f2a5"}]},{"style":"normal","_key":"11a417210fcb","markDefs":[{"blank":true,"_type":"link","href":"https://www.rejoynhcp.com/Clinician-Brief-Summary.pdf","_key":"6a02275e719a"}],"children":[{"_type":"span","marks":[],"text":"10. Rejoyn. Clinician brief summary. Otsuka America Pharmaceutical, Inc. 2024. Accessed November 7, 2024. ","_key":"80848561f9e60"},{"_type":"span","marks":["6a02275e719a"],"text":"https://www.rejoynhcp.com/Clinician-Brief-Summary.pdf","_key":"80848561f9e61"}],"_type":"block"},{"_type":"block","style":"normal","_key":"c9c6c37df511","markDefs":[{"blank":true,"_type":"link","href":"https://www.healthcare-brew.com/stories/2024/07/22/cms-proposed-reimbursement-codes-digital-therapeutics-industry","_key":"015bb7157e79"}],"children":[{"_type":"span","marks":[],"text":"11. Anderson M. What CMS’s proposed reimbursement codes could mean for the digital therapeutics industry. HealthCare Brew. July 22, 2024. Accessed November 7, 2024. ","_key":"ea9e67f514d50"},{"text":"https://www.healthcare-brew.com/stories/2024/07/22/cms-proposed-reimbursement-codes-digital-therapeutics-industry","_key":"ea9e67f514d51","_type":"span","marks":["015bb7157e79"]}]}],"gptSummary":"Bipolar mixed states share symptoms with PTSD, GAD, ADD, and borderline personality disorder, complicating diagnosis. Four strategies to manage this uncertainty include gathering comprehensive data, involving patients and families in decision-making, initiating psychotherapy (including digital therapeutics), and comparing treatment risks. Gathering data involves using tools like the \"MoodCheck\" questionnaire. Patient education and reliable internet resources are crucial. Digital therapeutics offer promising alternatives to traditional therapy, with new CPT codes proposed for reimbursement. These strategies aim to improve diagnostic accuracy and treatment outcomes in complex mood disorders.","taxonomyMapping":[{"parent":{"_rev":"uvXJooXtzvjNOyx50HTt8m","_updatedAt":"2023-03-31T19:15:59Z","_createdAt":"2020-03-26T06:11:21Z","parent":null,"_type":"taxonomy","name":"Topics","_id":"pst_taxonomy_53202_clinical","identifier":"topics","isMainTopic":true},"_createdAt":"2020-03-26T06:11:21Z","name":"Bipolar 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After 2 failed antidepressant trials, a different therapeutic modality might be beneficial, including TMS.","_key":"1d20b4e15a220"},{"marks":["superscript"],"text":"2","_key":"8d2023545ca0","_type":"span"}]},{"markDefs":[],"children":[{"marks":[],"text":"","_key":"343b05c8d4dc0","_type":"span"}],"_type":"block","style":"normal","_key":"0133f2f3183c"},{"_key":"be3c4a50b4db","markDefs":[],"children":[{"text":"The Inspire system allows clinicians to provide easy to use, cost effective, portable, high-power, air-cooling, back-to-back customizable TMS treatments. The Inspire system is built using Magstim TMS technology, which is cited in more than 20,000 peer reviewed research papers. It is used in hospitals, clinics, and research centers worldwide. The system also leverages intuitive preset clinical workflows to simplify the treatment process, and delivers precise results with no pulse decay, ensuring the correct dosage. Magstim’s air-cooled coil reduces downtime and eliminates additional cooling expenses. Furthermore, its advanced data analytics tools improve the efficacy of the treatment.","_key":"ca977f7168810","_type":"span","marks":[]}],"_type":"block","style":"normal"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"2775eb0637110"}],"_type":"block","style":"normal","_key":"e8a45ab03972"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"TMS is now mostly covered by insurance, including Medicare. Additionally, the range of clinicians available to utilize TMS has expanded: many states now permit both psychiatrists and psychiatric nurse practitioners to prescribe and treat patients with TMS.","_key":"3fcc15322f8a0"}],"_type":"block","style":"normal","_key":"feca110242a1"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"2364098bb5f80"}],"_type":"block","style":"normal","_key":"910fba3ea6b5"},{"_key":"e6aa08b46f4e","markDefs":[],"children":[{"_type":"span","marks":[],"text":"Earlier this year, the FDA granted clearance to Magstim’s TMS technology, Horizon 3.0 with StimGuide Pro, which is indicated for adults with MDD who failed to achieve improvement from prior antidepressant trials, and for adults with OCD. Horizon 3.0 with StimGuide Pro is the first integrated TMS system with navigation, adding new advanced camera technology designed to allow for precise treatment targeting and a central screen intended to reduce complexity. The Horizon 3.0 TMS Therapy System has also received prior clearance for decreasing comorbid anxiety symptoms in adults with MDD.","_key":"d8b277b433540"},{"_type":"span","marks":["superscript"],"text":"3","_key":"f3016e716505"}],"_type":"block","style":"normal"},{"_key":"1180f5f3f3a4","markDefs":[],"children":[{"text":"","_key":"c8c35265901d0","_type":"span","marks":[]}],"_type":"block","style":"normal"},{"markDefs":[],"children":[{"_key":"d3b3092165450","_type":"span","marks":[],"text":"“We are passionate about helping patients worldwide to improve their mental health,” said Stolec-Campo. “We worked with leading psychiatrists, clinicians, and researchers to develop this system, enabling advanced treatments and simplified practice workflows. 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We strive to provide the best technology for our patients.”","_key":"52d407ed17c80"},{"text":"3","_key":"dbcf56d89d93","_type":"span","marks":["superscript"]}],"_type":"block","style":"normal","_key":"c8b6c205010a","markDefs":[]},{"_key":"b3d33919e823","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"2ca4777b5db30"}],"_type":"block","style":"normal"},{"style":"normal","_key":"09ef262e3ef7","markDefs":[],"children":[{"_type":"span","marks":[],"text":"“Magstim engineered the very first commercially available TMS research technology, and we remain committed to our foundation of research,” said Stolec-Campo. “We are unique in the industry because we do not charge pay per use fees, we maintain a dedicated service and support team, and we manufacture our own technology.”","_key":"9bc265a7906e0"},{"_type":"span","marks":["superscript"],"text":"1","_key":"d5d95612d94e"}],"_type":"block"},{"_key":"cbaabaea23f8","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"cd374e6d440a0"}],"_type":"block","style":"normal"},{"_key":"88a4534699cd","markDefs":[],"children":[{"text":"References","_key":"a0665909f4ec0","_type":"span","marks":["strong"]}],"_type":"block","style":"normal"},{"_key":"e77efa96b8e9","markDefs":[{"href":"https://finance.yahoo.com/news/fda-clears-magstim-horizon-inspire-131100376.html?guccounter=1\u0026guce_referrer=aHR0cHM6Ly93d3cuZ29vZ2xlLmNvbS8\u0026guce_referrer_sig=AQAAADsGQh9CoEGLER07kXOIc75FwG-YYZHAb0JfFDPBsaE40Ac9rHzacpO2L9u5AYq1V4s6tA0AAuxdM5Gzb49f0MSl2D-OJjE871sltULYhbWs4bB_dM6oZ-3rkFjpTBTDAtvfTgvDRjHRJCdim5A5qN_X_JEII5G2g-6wWyevN3Ff","_key":"36d17c602377","blank":true,"_type":"link"}],"children":[{"_type":"span","marks":[],"text":"1. FDA clears Magstim Horizon INSPIRE transcranial magnetic stimulation system to treat depression, OCD, anxious depression. News release. November 12, 2024. ","_key":"f35b0ffa3e310"},{"_type":"span","marks":["36d17c602377"],"text":"https://finance.yahoo.com/news/fda-clears-magstim-horizon-inspire-131100376.html","_key":"f35b0ffa3e311"}],"_type":"block","style":"normal"},{"_key":"95eb06a076ed","markDefs":[{"blank":true,"_type":"link","href":"https://www.psychiatrictimes.com/view/rtms-for-antidepressant-nonresponders","_key":"a468a014ba90"}],"children":[{"_key":"3861811a31af0","_type":"span","marks":[],"text":"2. Miller B. rTMS for Antidepressant Nonresponders. "},{"_type":"span","marks":["em"],"text":"Psychiatric Times","_key":"3861811a31af1"},{"_type":"span","marks":[],"text":". October 21, 2024. ","_key":"3861811a31af2"},{"text":"https://www.psychiatrictimes.com/view/rtms-for-antidepressant-nonresponders","_key":"3861811a31af3","_type":"span","marks":["a468a014ba90"]}],"_type":"block","style":"normal"},{"_key":"a11207a97b0c","markDefs":[{"href":"https://www.psychiatrictimes.com/view/first-integrated-tms-system-for-major-depressive-disorder-obsessive-compulsive-disorder","_key":"212835582b5a","blank":true,"_type":"link"}],"children":[{"_type":"span","marks":[],"text":"3. Kuntz L. First integrated TMS system for major depressive disorder, obsessive-compulsive disorder. ","_key":"003570dc0fa70"},{"_type":"span","marks":["em"],"text":"Psychiatric Times","_key":"003570dc0fa71"},{"_type":"span","marks":[],"text":". January 30, 2024. 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customizable, portable, and cost-effective TMS treatments, supported by extensive research and advanced data analytics.\n\n• Magstim's Horizon 3.0 system features advanced navigation technology, enhancing treatment precision and simplifying clinical workflows.","articleType":"News","audioUrl":"https://s3.us-east-1.amazonaws.com/ai-generated-audios/www.psychiatrictimes.com/55de9bd1-c137-429f-90ab-a97e2e58d046_1731440583723.603a8c1b-461b-4c5f-9f6d-4715e7cee49c.mp3","authors":[{"displayName":"Leah Kuntz","url":"leah-kuntz"}],"documentGroup":null,"contentCategory":{"_type":"contentCategory","name":"Articles","_id":"8bdaa7fc-960a-4b57-b076-75fdce3741bb","_updatedAt":"2020-02-25T09:35:56Z","_createdAt":"2020-02-06T09:15:47Z","_rev":"snQqhhB4O8T5bi1viURsgs"},"_id":"55de9bd1-c137-429f-90ab-a97e2e58d046","_createdAt":"2024-11-12T19:42:54Z","title":"Newly FDA-Cleared TMS for Major Depressive Disorder, Obsessive-Compulsive Disorder, and Anxious 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","url":{"current":"differential-diagnosis-of-mixed-states-is-nearly-impossible-heres-how-to-cope","_type":"slug"},"thumbnail":{"_type":"mainImage","alt":"questions","caption":"sergign/AdobeStock","asset":{"_ref":"image-0ed42755e5073b545ec9cabf17e17101c1af23d2-4000x2667-jpg","_type":"reference"}},"published":"2024-11-12T15:00:00.000Z"}]},{"body":[{"disableTextWrap":false,"disableLightBox":true,"alt":"questions","imgcaption":[{"markDefs":[],"children":[{"marks":[],"text":"sergign/AdobeStock","_key":"74efa4830b5e0","_type":"span"}],"_type":"block","style":"normal","_key":"427f5aada048"}],"asset":{"_ref":"image-0ed42755e5073b545ec9cabf17e17101c1af23d2-4000x2667-jpg","_type":"reference"},"_key":"e018e0b3ac21","alignment":"left","widthP":50,"_type":"figure"},{"markDefs":[{"href":"https://www.psychiatrictimes.com/topics/ptsd","_key":"6feebe99dafd","nofollow":true,"blank":true,"_type":"link"}],"children":[{"_type":"span","marks":[],"text":"This first of 3 articles will demonstrate that bipolar mixed states are nearly impossible to differentiate from depression that is comorbid with ","_key":"44f622088b110"},{"marks":["6feebe99dafd"],"text":"posttraumatic stress disorder","_key":"fdd2b88018b6","_type":"span"},{"_type":"span","marks":[],"text":" (PTSD), or generalized anxiety disorder (GAD), or attention-deficit disorder (ADD). Parts 2 and 3 will present 4 ways of coping with uncertainty when faced with this difficult differential.","_key":"60436d9e5985"}],"_type":"block","style":"normal","_key":"1fb026c784ca"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"9deb883f27580"}],"_type":"block","style":"normal","_key":"894b98c5e77b"},{"markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"The Mixed Features Specifier","_key":"6127deb56eea0"}],"_type":"block","style":"normal","_key":"097dc5f3b014"},{"_type":"block","style":"normal","_key":"61b36b70f904","markDefs":[{"nofollow":true,"blank":true,"_type":"link","href":"https://www.psychiatrictimes.com/topics/major-depressive-disorder","_key":"c3f6fe514229"}],"children":[{"_type":"span","marks":[],"text":"In 2013, the ","_key":"30bf705385c30"},{"_type":"span","marks":["em"],"text":"DSM-5","_key":"30bf705385c31"},{"_type":"span","marks":[],"text":" extended the bipolar spectrum all the way to “unipolar” (","_key":"30bf705385c32"},{"_type":"span","marks":["c3f6fe514229"],"text":"major depressive disorder","_key":"c91cebd0f16c"},{"marks":[],"text":", MDD). The mixed features specifier means that individuals who do not have bipolar disorder can have manic symptoms. But which symptoms and how many? Broadening the answer broadens overlap with other conditions.","_key":"80056bfa6b54","_type":"span"}]},{"style":"normal","_key":"0f4f2c7bf720","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"3680c918333d0"}],"_type":"block"},{"style":"normal","_key":"3f53cb9fc7d5","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Which Symptoms?","_key":"48637dc11e5b0"}],"_type":"block"},{"markDefs":[],"children":[{"_key":"5fac634596b20","_type":"span","marks":[],"text":"In the words of some of the of the "},{"marks":["em"],"text":"DSM-5 ","_key":"5fac634596b21","_type":"span"},{"_type":"span","marks":[],"text":"crafters: “The mixed features specifier, it was decided, would define clinical entities … that merited clear and more precise definition—especially in order to ","_key":"5fac634596b22"},{"_type":"span","marks":["em"],"text":"establish clear entities for future outcome studies","_key":"5fac634596b23"},{"_type":"span","marks":[],"text":".”","_key":"5fac634596b24"},{"_type":"span","marks":["superscript"],"text":"1","_key":"a78fdb3fb139"},{"_type":"span","marks":[],"text":" [emphasis mine] In other words, the new criteria were more a research guideline than a clinical guideline.","_key":"440b4b104242"}],"_type":"block","style":"normal","_key":"49751ce53d5c"},{"_type":"block","style":"normal","_key":"762764c75e70","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"bf3aa43e992a0"}]},{"markDefs":[],"children":[{"text":"This helps explain the exclusion of some of the high-energy symptoms commonly observed in research on mixed states since 2013. According to three such studies,","_key":"90a8ddb8e7830","_type":"span","marks":[]},{"_key":"f07d368f97d2","_type":"span","marks":["superscript"],"text":"2-4"},{"_type":"span","marks":[],"text":" common symptoms of mixed states include:","_key":"20bf79f2973d"}],"_type":"block","style":"normal","_key":"59d2c6a123d3"},{"style":"normal","_key":"52313093d9a2","listItem":"bullet","markDefs":[],"children":[{"_key":"ec326abfbaf20","_type":"span","marks":[],"text":"Agitation, both psychic (anxiety) and physical"}],"level":1,"_type":"block"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"Irritability","_key":"53ef1f4683b30"}],"level":1,"_type":"block","style":"normal","_key":"436f140cdb65","listItem":"bullet"},{"markDefs":[],"children":[{"marks":[],"text":"Nonstop ideas and distractibility","_key":"87be4f9619ed0","_type":"span"}],"level":1,"_type":"block","style":"normal","_key":"a912666c4707","listItem":"bullet"},{"listItem":"bullet","markDefs":[],"children":[{"_type":"span","marks":[],"text":"Decreased sleep","_key":"91e2439ba3430"}],"level":1,"_type":"block","style":"normal","_key":"dee860043232"},{"_type":"block","style":"normal","_key":"a5b2bbb9b57e","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"d02f5f26a0960"}]},{"_key":"175235fd3736","markDefs":[],"children":[{"_type":"span","marks":[],"text":"Roger McIntyre, coauthor of one of those studies4 suggests these be remembered as “The 4 A’s”: anxiety, anger, agitation and attention problems. (Evidently including insomnia would ruin a good acronym).","_key":"6ee014f46e070"}],"_type":"block","style":"normal"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"1205afaf20b10"}],"_type":"block","style":"normal","_key":"eb3d2c02451d"},{"children":[{"marks":["strong"],"text":"How Many?","_key":"65a0e45587150","_type":"span"}],"_type":"block","style":"normal","_key":"7aa52566c9be","markDefs":[]},{"_key":"bfcb72eba6eb","markDefs":[{"nofollow":true,"blank":true,"_type":"link","href":"https://www.psychiatrictimes.com/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Ff1e3b9dd4ffeae34f537001797be01c2ea6cdc5e-690x482.png%3Ffit%3Dcrop%26auto%3Dformat\u0026w=1920\u0026q=75","_key":"70622a62e60c"}],"children":[{"marks":[],"text":"Three treatment guidelines for mixed states published since 2017 suggest that any admixture of manic and depressive symptoms is possible.","_key":"2eda03a95c9a0","_type":"span"},{"_type":"span","marks":["superscript"],"text":"5-7","_key":"98f9c926ee3a"},{"_type":"span","marks":[],"text":" This dimensional view is shown in the ","_key":"6d4cd368663a"},{"_type":"span","marks":["strong","70622a62e60c"],"text":"Figure","_key":"2eda03a95c9a1"},{"_type":"span","marks":[],"text":".","_key":"2eda03a95c9a2"},{"_type":"span","marks":["superscript"],"text":"8","_key":"d43be1daba0a"}],"_type":"block","style":"normal"},{"blank":true,"widthP":50,"disableTextWrap":false,"asset":{"_type":"reference","_ref":"image-f1e3b9dd4ffeae34f537001797be01c2ea6cdc5e-690x482-png"},"_type":"figure","alt":"Figure. A Dimensional View of Mixed States","alignment":"right","disableLightBox":true,"imgcaption":[{"children":[{"marks":["strong"],"text":"Figure.","_key":"e56fda3bddfa0","_type":"span"},{"_type":"span","marks":[],"text":" A Dimensional View of Mixed States","_key":"692fbf6cfc15"}],"_type":"block","style":"normal","_key":"e54c273880ac","markDefs":[]}],"_key":"e0919b735d37"},{"style":"normal","_key":"28a0f368cc73","markDefs":[],"children":[{"text":"In this view, there is no lower limit on the number of manic symptoms necessary to make an otherwise “unipolar” depression a mixed depression. This compounds the problem that the ","_key":"3a0ab0055d1f0","_type":"span","marks":[]},{"_type":"span","marks":["em"],"text":"DSM-5","_key":"3a0ab0055d1f1"},{"_key":"3a0ab0055d1f2","_type":"span","marks":[],"text":" authors were trying to avoid: overlapping symptoms."}],"_type":"block"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"09f283e8a5010"}],"_type":"block","style":"normal","_key":"4d699b15c278"},{"markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Overlap With Common Conditions","_key":"91fa4844cc2f0"}],"_type":"block","style":"normal","_key":"52328c735351"},{"markDefs":[{"nofollow":true,"blank":true,"_type":"link","href":"https://www.psychiatrictimes.com/_next/image?url=https%3A%2F%2Fcdn.sanity.io%2Fimages%2F0vv8moc6%2Fpsychtimes%2Fd030bfc505bdc5e912f1a3d8da755ba41dc254b9-624x304.png%3Ffit%3Dcrop%26auto%3Dformat\u0026w=1920\u0026q=75","_key":"00e550146000"}],"children":[{"_type":"span","marks":[],"text":"Several common conditions share nearly every symptom with bipolar mixed states, when the latter are defined as including the 4 A’s. These include depression with PTSD, GAD, or ADD, and borderline personality disorder. This overlap is shown in the ","_key":"3988f7f80a0e0"},{"_type":"span","marks":["strong","00e550146000"],"text":"Table","_key":"3988f7f80a0e1"},{"marks":[],"text":" (symptoms of MDD are shown in blue).","_key":"3988f7f80a0e2","_type":"span"}],"_type":"block","style":"normal","_key":"c3bff32ee2fd"},{"disableLightBox":true,"_type":"figure","alt":"Table. Overlap With Common Conditions","imgcaption":[{"style":"normal","_key":"dc79e72c720e","markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"Table. 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Response to previous treatments may be illuminating, but you might be the first provider.","_key":"e00ed7c5bee80","_type":"span"}]},{"markDefs":[],"children":[{"marks":[],"text":"","_key":"3cc206c717580","_type":"span"}],"_type":"block","style":"normal","_key":"dcb9e1884977"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"Is this “farewell to differential diagnosis,” as one author lamented?9 Not necessarily; rather, one can simply acknowledge that diagnostic certainty is almost impossible to attain in the face of depression with anxiety or anger or agitation or attention problems. When dealing with these symptoms, one must think of diagnoses in this context as ","_key":"ce646d5f4c280"},{"_type":"span","marks":["em"],"text":"tentative","_key":"ce646d5f4c281"},{"_type":"span","marks":[],"text":", holding open the possibility of alternative explanations until a good outcome is obtained.","_key":"ce646d5f4c282"}],"_type":"block","style":"normal","_key":"023ad74e5dc9"},{"_key":"161a6beed092","markDefs":[],"children":[{"marks":[],"text":"","_key":"108c8aea94a00","_type":"span"}],"_type":"block","style":"normal"},{"_type":"block","style":"normal","_key":"82b770c020ff","markDefs":[],"children":[{"text":"Coping With Diagnostic Uncertainty","_key":"213c27ec64940","_type":"span","marks":["strong"]}]},{"children":[{"marks":[],"text":"Here are 4 steps to take or consider before initiating treatment that can help manage diagnostic uncertainty.","_key":"3fed91887d020","_type":"span"}],"_type":"block","style":"normal","_key":"99f8b3e29e2b","markDefs":[]},{"markDefs":[],"children":[{"_key":"a474ebbea0ed0","_type":"span","marks":[],"text":"1. "},{"_type":"span","marks":["em"],"text":"Routinely gather data","_key":"a474ebbea0ed1"},{"_type":"span","marks":[],"text":" that differentiate bipolar and unipolar depressions: family history, age of onset of depression, illness course (episodic or postpartum), and response to treatment (especially adverse responses to antidepressants).","_key":"a474ebbea0ed2"}],"_type":"block","style":"normal","_key":"dd7ae6e4c1fd"},{"style":"normal","_key":"3551645b5866","markDefs":[],"children":[{"_type":"span","marks":[],"text":"2. ","_key":"ca62a65d4c200"},{"_type":"span","marks":["em"],"text":"Engage the patient","_key":"ca62a65d4c201"},{"_key":"ca62a65d4c202","_type":"span","marks":[],"text":" (and perhaps family) in shared decision-making through psychoeducation. Help them understand that the possibility of bipolar should be approached not as a categorical yes-or-no but dimensionally, as in “how much bipolarity might you have, if any?”"}],"_type":"block"},{"_key":"b17d06a2bbe9","markDefs":[],"children":[{"_type":"span","marks":[],"text":"3. ","_key":"1b5b081af7a70"},{"_type":"span","marks":["em"],"text":"Consider beginning with psychotherapy","_key":"1b5b081af7a71"},{"_type":"span","marks":[],"text":". If you do not offer psychotherapy yourself and cannot easily refer for it, there are now inexpensive digital therapies for depression, PTSD, anxiety, and ADD. There is also a simple initial behavioral therapy for bipolarity, social rhythm therapy.","_key":"1b5b081af7a72"}],"_type":"block","style":"normal"},{"style":"normal","_key":"c5d6f7477039","markDefs":[],"children":[{"_type":"span","marks":[],"text":"4. 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For example, though it may not be clear if a patient has a truly unipolar depression or a bipolar depression, the risks of antidepressants and lamotrigine are both relevant to an initial treatment decision.","_key":"d603061d42a82"}],"_type":"block"},{"style":"normal","_key":"697478050bb7","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"9df0ac389bf40"}],"_type":"block"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"More on each of these approaches follows in Part 2, including practical clinical tools for each.","_key":"26d77f1cb5ec0"}],"_type":"block","style":"normal","_key":"5fb041e0213b"},{"children":[{"_type":"span","marks":[],"text":"","_key":"2d34923151370"}],"_type":"block","style":"normal","_key":"51e87d5c7f48","markDefs":[]},{"style":"normal","_key":"9510c309631a","markDefs":[{"_type":"link","href":"https://wwnorton.com/books/A-Spectrum-Approach-to-Mood-Disorders/","_key":"5d71b04ccb28"},{"_type":"link","href":"https://wwnorton.com/books/Bipolar-Not-So-Much/","_key":"3a0716fd7b8a"}],"children":[{"_type":"span","marks":["strong"],"text":"Dr Phelps","_key":"a984a48aec0f0"},{"_type":"span","marks":[],"text":" ","_key":"a984a48aec0f1"},{"_type":"span","marks":["em"],"text":"is retiring from 30 years of treating complex mood disorders, and recently founded another website, DepressionEducation.org. 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