PRACTICE GUIDELINE FOR THE Treatment of Patients With Major Depressive Disorder Third Edition WORK GROUP ON MAJOR DEPRESSIVE DISORDER Alan J. Gelenberg, M.D., Chair Marlene P. Freeman, M.D. John C. Markowitz, M.D. Jerrold F. Rosenbaum, M.D. Michael E. Thase, M.D. Madhukar H. Trivedi, M.D. Richard S. Van Rhoads, M.D., Consultant INDEPENDENT REVIEW PANEL Victor I. Reus, M.D., Chair J. Raymond DePaulo, Jr., M.D. Jan A. Fawcett, M.D. Christopher D. Schneck, M.D. David A. Silbersweig, M.D. This practice guideline was approved in May 2010 and published in October 2010. A guideline watch, summarizing significant developments in the scientific literature since publication of this guideline, may be available at http://www.psychiatryonline.com/pracGuide/pracGuideTopic_7.aspx. Copyright 2010, American Psychiatric Association. APA makes this practice guideline freely available to promote its dissemination and use; however, copyright protections are enforced in full. No part of this guideline may be reproduced except as permitted under Sections 107 and 108 of U.S. Copyright Act. For permission for reuse, visit APPI Permissions & Licensing Center at http://www.appi.org/CustomerService/Pages/Permissions.aspx. FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST The Work Group on Major Depressive Disorder reports reports receiving honoraria from lectureships for Boeh- the following potentially competing interests for the pe- ringer Ingleheim, Bristol-Myers Squibb, Cyberonics, riod from May 2005 to May 2010: Forest Pharmaceuticals, Inc., Eli Lilly and Company, and Dr. Gelenberg reports consulting for Eli Lilly and Com- Schwartz Pharma. He was involved in the creation of pany, Pfizer, Best Practice, AstraZeneca, Wyeth, Cyber- the Massachusetts General Hospital Psychiatry Academy onics, Novartis, Forest Pharmaceuticals, Inc., GlaxoSmith- (MGH-PA) and has served as a panelist in four satellite Kline, ZARS Pharma, Jazz Pharmaceuticals, Lundbeck, broadcast programs. MGH-PA programs that have indus- Takeda Pharmaceuticals North America, Inc., eResearch try support are always multi-sponsored, and curriculum Technology, Dey Pharma, PGxHealth, and Myriad Genet- development by the Academy is independent of sponsor- ics. He reports serving on speakers bureaus for Pfizer, ship; the curricula from January 2005 to March 2009 in- GlaxoSmithKline, and Wyeth. He reports receiving re- cluded sponsorship support from AstraZeneca, Bristol- search grant funding from Eli Lilly and Company, Pfizer, Myers Squibb, Cephalon, Eli Lilly and Company, Forest and GlaxoSmithKline. He reports stock ownership in Pharmaceuticals, Inc., GlaxoSmithKline, Janssen Medical Healthcare Technology Systems. Affairs LLC, Ortho-McNeil Pharmaceutical, sanofi- Dr. Freeman reports that she received research support aventis, Shire, and Wyeth. He reports equity holdings in from the Meadows Foundation, the National Institute for Compellis Pharmaceuticals, MedAvante, and Somaxon. Mental Health, the U.S. Food and Drug Administration, Dr. Thase reports that he provided scientific consulta- the Institute for Mental Health Research, Forest, Glaxo- tion to AstraZeneca, Bristol-Myers Squibb, Eli Lilly & SmithKline and Eli Lilly and Company (investigator- Company, Forest Pharmaceuticals, Inc., Gerson Lehman initiated trials), and Pronova Biocare (research materials). Group, GlaxoSmithKline, Guidepoint Global, H. Lund- She received an honorarium for case-based peer-reviewed beck A/S, MedAvante, Inc., Neuronetics, Inc., Novartis, material for AstraZeneca’s website. She reports consulting Otsuka, Ortho-McNeil Pharmaceuticals, PamLab, L.L.C., for Ther-Rx, Reliant, and Pamlab. She reports receiving Pfizer (formerly Wyeth-Ayerst Laboratories), Schering- an honorarium for speaking at an APA continuing medical Plough (formerly Organon), Shire U.S., Inc., Supernus education program that was sponsored by Forest and an Pharmaceuticals, Takeda (Lundbeck), and Transcept Phar- honorarium for speaking at a continuing medication edu- maceuticals. He was a member of the speakers bureaus for cation program sponsored by KV Pharmaceuticals. She AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Com- reports receiving an honorarium from Leerink Swann for pany, GlaxoSmithKline, Pfizer (formerly Wyeth-Ayerst participating in a focus group. Laboratories), and Schering-Plough (formerly Organon). Dr. Markowitz reports consulting for Ono Pharma- He received grant funding from Eli Lilly and Company, ceutical Co., Ltd. (2005). He reports receiving research GlaxoSmithKline, the National Institute of Mental Health, support from Forest Pharmaceuticals, Inc. (2005). He re- the Agency for Healthcare Research and Quality, and ports receiving grant support from the National Institute Sepracor, Inc. He had equity holdings in MedAvante, Inc., of Mental Health (2005–2013), the National Alliance for and received royalty income from American Psychiatric Research in Schizophrenia and Depression (2005), and Publishing, Inc., Guilford Publications, Herald House, MINT: Mental Health Initiative (2005). He reports re- Oxford University Press, and W.W. Norton and Company. ceiving royalties from American Psychiatric Publishing, Inc. His wife was employed as the group scientific director for (2005–2010), Basic Books (2005–2010), Elsevier (2005– Embryon (formerly Advogent), which does business with 2010), and Oxford University Press (2007–2010). Bristol-Myers Squibb and Pfizer/Wyeth. Dr. Rosenbaum reports attending advisory boards for Dr. Trivedi reports that he was a consultant to or on Bristol-Myers Squibb, Cephalon, Cyberonics, Forest Phar- speaker bureaus for Abbott Laboratories, Inc., Abdi Ibra- maceuticals, Inc., Eli Lilly and Company, MedAvante, him, Akzo (Organon Pharmaceuticals, Inc.), AstraZeneca, Neuronetics, Inc., Novartis, Orexigen Therapeutics, Inc., Bristol-Myers Squibb Company, Cephalon, Inc., Cyber- Organon BioSciences, Pfizer, Roche Diagnostics, Sanofi- onics, Inc., Eli Lilly and Company, Evotec, Fabre Kramer aventis, Shire, and Wyeth. He reports consulting for Aus- Pharmaceuticals, Inc., Forest Pharmaceuticals, Glaxo- pex Pharmaceuticals, Compellis Pharmaceuticals, EPIX SmithKline, Janssen Pharmaceutica Products, L.P., Johnson Pharmaceuticals, Neuronetics, Inc., Organon BioSci- & Johnson P.R.D., Meade-Johnson, Medtronic, Neuro- ences, Somaxon, and Supernus Pharmaceuticals, Inc. He netics, Otsuka Pharmaceuticals, Parke-Davis Pharmaceuti- Copyright 2010, American Psychiatric Association. APA makes this practice guideline freely available to promote its dissemination and use; however, copyright protections are enforced in full. No part of this guideline may be reproduced except as permitted under Sections 107 and 108 of U.S. Copyright Act. For permission for reuse, visit APPI Permissions & Licensing Center at http://www.appi.org/CustomerService/Pages/Permissions.aspx. cals, Inc., Pfizer, Inc., Sepracor, Shire Development, Solvay competing interests. The Independent Review Panel re- Pharmaceuticals, VantagePoint, and Wyeth-Ayerst Labo- viewed this guideline to assess potential biases and found ratories. He received research support from the Agency for no evidence of influence from the industry and other re- Healthcare Research and Quality, Corcept Therapeutics, lationships of the Work Group disclosed above. The Inc., Cyberonics, Inc., Merck, National Alliance for Re- Steering Committee on Practice Guidelines also reviewed search in Schizophrenia and Depression, National Insti- this guideline and found no evidence of influence from tute of Mental Health, National Institute on Drug Abuse, these relationships. The development process for this Novartis, Pharmacia & Upjohn, Predix Pharmaceuticals guideline, including the roles of the Work Group, Inde- (Epix), Solvay Pharmaceuticals, Inc., and Targacept. pendent Review Panel, Steering Committee, APA Assem- Dr. Van Rhoads reports no competing interests. bly, and APA Board of Trustees is described in “Overview The Independent Review Panel, including Drs. Reus, of Guideline Development Process” on p. 11. DePaulo, Fawcett, Schneck, and Silbersweig, report no Copyright 2010, American Psychiatric Association. APA makes this practice guideline freely available to promote its dissemination and use; however, copyright protections are enforced in full. No part of this guideline may be reproduced except as permitted under Sections 107 and 108 of U.S. Copyright Act. For permission for reuse, visit APPI Permissions & Licensing Center at http://www.appi.org/CustomerService/Pages/Permissions.aspx. AMERICAN PSYCHIATRIC ASSOCIATION STEERING COMMITTEE ON PRACTICE GUIDELINES John S. McIntyre, M.D., Chair (1999–2009), Consultant (2009–2010) Joel Yager, M.D., Vice-Chair (2008–2009), Chair (2009–2010) Daniel J. Anzia, M.D. Thomas J. Craig, M.D., M.P.H. Molly T. Finnerty, M.D. Bradley R. Johnson, M.D. Francis G. Lu, M.D. James E. Nininger, M.D., Vice-Chair (2009–2010) Barbara Schneidman, M.D. Paul Summergrad, M.D. Sherwyn M. Woods, M.D., Ph.D. Michael J. Vergare, M.D. M. Justin Coffey, M.D. (fellow) Kristen Ochoa, M.D. (fellow) Jeremy Wilkinson, M.D. (fellow) Sheila Hafter Gray, M.D. (liaison) STAFF Robert Kunkle, M.A., Director, Practice Guidelines Project Robert M. Plovnick, M.D., M.S., Director, Dept. of Quality Improvement and Psychiatric Services Darrel A. Regier, M.D., M.P.H., Director, Division of Research MEDICAL EDITOR Laura J. Fochtmann, M.D. Copyright 2010, American Psychiatric Association. APA makes this practice guideline freely available to promote its dissemination and use; however, copyright protections