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Symptoms can lead to significant disability, which result in impairments in overall quality of life. Though there are many approved antidepressant treatments for depression\u2014including selective serotonin reuptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors\u2014about a third of patients do not respond to these medications. Therefore, it is imperative for drug discovery to continue towards the development of novel and rapidly acting compounds, especially for patients with treatment-resistant depression. After a brief review of the efficacy of approved antidepressant therapies, we will discuss experimental medication treatments for depression. Specifically, we examine novel medications that are thought to primarily modulate the glutamatergic, cholinergic and opioid systems to achieve antidepressant efficacy. We also give examples of anti-inflammatories, neurokinin-1 modulators, vasopressin antagonists and neurogenesis enhancers that may have a therapeutic role in treatment-resistant depression. The current pipeline of antidepressant treatments is shifting towards medications with novel mechanisms, which may lead to important, life-changing discoveries for patients with severe disease.<\/jats:p>","DOI":"10.1038\/tp.2017.33","type":"journal-article","created":{"date-parts":[[2017,3,21]],"date-time":"2017-03-21T22:45:10Z","timestamp":1490136310000},"page":"e1068-e1068","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Experimental medication treatment approaches for depression"],"prefix":"10.1038","volume":"7","author":[{"given":"D F","family":"Ionescu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G I","family":"Papakostas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,21]]},"reference":[{"key":"BFtp201733_CR1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.4088\/JCP.14m09298","volume":"76","author":"PE Greenberg","year":"2015","unstructured":"Greenberg PE, Fournier AA, Sisitsky T, Pike CT, Kessler RC . 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Lundbeck A\/S, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Novartis Pharma AG, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Shire Pharmaceuticals, Sunovion Pharmaceuticals, Takeda Pharmaceutical Company, Theracos and Wyeth. GIP has received honoraria from Abbott Laboratories, AstraZeneca PLC, Avanir Pharmaceuticals, Bristol-Myers Squibb Company, Brainsway, Cephalon, Dey Pharma, L.P., Eli Lilly, Evotec AG, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, H. Lundbeck A\/S, Novartis Pharma AG, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics, Shire Pharmaceuticals, Sunovion Pharmaceuticals, Takeda Pharmaceutical Company, Theracos, Titan Pharmaceuticals and Wyeth. GIP has received research support from AstraZeneca PLC, Bristol-Myers Squibb Company, Forest Pharmaceuticals, the National Institute of Mental Health, PAMLAB LLC, Pfizer, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Sunovion Pharmaceuticals and Theracos. GIP has served (not currently) on the speaker\u2019s bureau for BristolMyersSquibb and Pfizer. DFI has received research funding from a Young Investigator Award through the Brain and Behavior Research Foundation, KL2\/CMeRIT Award from the Harvard Catalyst, the NIMH\/NIH (K23MH107776-01) and from the Executive Committee on Research at Massachusetts General Hospital. DFI has received reimbursement from the FDA to attend meetings as part of the Psychopharmacologic Drugs Advisory Committee (PDAC).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}