Conflict of interest: HM: full time employee at Reviva Pharmaceuticals and was a full time employee of Aptinyx. He also is the owner of Murck-Neuroscience LLC, which develops a patent in the area of major depression. MF: lifetime disclosures: Research Support: Abbott Laboratories; Acadia Pharmaceuticals; Alkermes, Inc.; American Cyanamid; Aspect Medical Systems; AstraZeneca; Avanir Pharmaceuticals; AXSOME Therapeutics; BioClinica, Inc; Biohaven; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Centrexion Therapeutics Corporation; Cephalon; Cerecor; Clarus Funds; Clexio Biosciences; Clintara, LLC; Covance; Covidien; Eli Lilly and Company;EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; FORUM Pharmaceuticals; Ganeden Biotech, Inc.; Gentelon, LLC; GlaxoSmithKline; Harvard Clinical Research Institute; Hoffman-LaRoche; Icon Clinical Research; Indivior; i3 Innovus/Ingenix; Janssen R&D, LLC; Jed Foundation; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Lundbeck Inc.; Marinus Pharmaceuticals; MedAvante; Methylation Sciences Inc; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Coordinating Center for Integrated Medicine (NiiCM); National Institute of Drug Abuse (NIDA); National Institutes of Health; National Institute of Mental Health (NIMH); Neuralstem, Inc.; NeuroRx; Novartis AG; Novaremed; Organon Pharmaceuticals; Otsuka Pharmaceutical Development, Inc.; PamLab, LLC.; Pfizer Inc.; Pharmacia-Upjohn; Pharmaceutical Research Associates., Inc.; Pharmavite® LLC; PharmoRx Therapeutics; Photothera; Praxis Precision Medicines; Premiere Research International; Protagenic Therapeutics, Inc.; Reckitt Benckiser; Relmada Therapeutics Inc.; Roche Pharmaceuticals; RCT Logic, LLC (formerly Clinical Trials Solutions, LLC); Sanofi-Aventis US LLC; Shenox Pharmaceuticals, LLC; Shire; Solvay Pharmaceuticals, Inc.; Stanley Medical Research Institute (SMRI); Synthelabo; Taisho Pharmaceuticals; Takeda Pharmaceuticals; Tal Medical; VistaGen; WinSanTor, Inc.; Wyeth- Ayerst Laboratories; Advisory Board/Consultant: Abbott Laboratories; Acadia; Aditum Bio Management Company, LLC; Affectis Pharmaceuticals AG; Alfasigma USA, Inc.; Alkermes, Inc.; Altimate Health Corporation; Amarin Pharma Inc.; Amorsa Therapeutics, Inc.; Ancora Bio, Inc.; Angelini S.p.A; Aptinyx Inc.; Arbor Pharmaceuticals, LLC; Aspect Medical Systems; Astella Pharma Global Development, Inc.; AstraZeneca; Auspex Pharmaceuticals; Avanir Pharmaceuticals; AXSOME Therapeutics; Bayer AG; Best Practice Project Management, Inc.; Biogen; BioMarin Pharmaceuticals, Inc.; BioXcel Therapeutics; Biovail Corporation; Boehringer Ingelheim; Boston Pharmaceuticals; BrainCells Inc; Bristol-Myers Squibb; Cambridge Science Corporation; CeNeRx BioPharma; Cephalon, Inc.; Cerecor; Clexio Biosciences; Click Therapeutics, Inc; CNS Response, Inc.; Compellis Pharmaceuticals; Cybin Corporation; Cypress Pharmaceutical, Inc.; DiagnoSearch Life Sciences (P) Ltd.; Dainippon Sumitomo Pharma Co. Inc.; Dr. Katz, Inc.; Dov Pharmaceuticals, Inc.; Edgemont Pharmaceuticals, Inc.; Eisai Inc.; Eli Lilly and Company; ElMindA; EnVivo Pharmaceuticals, Inc.; Enzymotec LTD; ePharmaSolutions; EPIX Pharmaceuticals, Inc.; Esthismos Research, Inc.; Euthymics Bioscience, Inc.; Evecxia Therapeutics, Inc.; ExpertConnect, LLC; FAAH Research Inc.; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; Forum Pharmaceuticals; Gate Neurosciences, Inc.; GenetikaPlus Ltd.; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH; Happify; H. Lundbeck A/S; Indivior; i3 Innovus/Ingenis; Intracellular; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc.; JDS Therapeutics, LLC; Johnson & Johnson Pharmaceutical Research & Development, LLC; Knoll Pharmaceuticals Corp.; Labopharm Inc.; Lorex Pharmaceuticals; Lundbeck Inc.; Marinus Pharmaceuticals; MedAvante, Inc.; Merck & Co., Inc.; Mind Medicine Inc.; MSI Methylation Sciences, Inc.; Naurex, Inc.; Navitor Pharmaceuticals, Inc.; Nestle Health Sciences; Neuralstem, Inc.; Neurocrine Biosciences, Inc.; Neuronetics, Inc.; NextWave Pharmaceuticals; Niraxx Light Therapeutics, Inc; Northwestern University; Novartis AG; Nutrition 21; Opiant Pharmecuticals; Orexigen Therapeutics, Inc.; Organon Pharmaceuticals; Osmotica; Otsuka Pharmaceuticals; Ovid Therapeutics, Inc.; Pamlab, LLC.; Perception Neuroscience; Pfizer Inc.; PharmaStar; PharmaTher Inc.; Pharmavite® LLC.; PharmoRx Therapeutics; Polaris Partners; Praxis Precision Medicines; Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc.; Protagenic Therapeutics, Inc; PPD; PThera, LLC; Purdue Pharma; Puretech Ventures; Pure Tech LYT, Inc.; PsychoGenics; Psylin Neurosciences, Inc.; RCT Logic, LLC ( formerly Clinical Trials Solutions, LLC); Relmada Therapeutics, Inc.; Rexahn Pharmaceuticals, Inc.; Ridge Diagnostics, Inc.; Roche; Sanofi-Aventis US LLC.; Sensorium Therapeutics; Sentier Therapeutics; Sepracor Inc.; Servier Laboratories; Schering-Plough Corporation; Shenox Pharmaceuticals, LLC; Solvay Pharmaceuticals, Inc.; Somaxon Pharmaceuticals, Inc.; Somerset Pharmaceuticals, Inc.; Sonde Health; Sunovion Pharmaceuticals; Supernus Pharmaceuticals, Inc.; Synthelabo; Taisho Pharmaceuticals; Takeda Pharmaceutical Company Limited; Tal Medical, Inc.; Tetragenex; Teva Pharmaceuticals; TransForm Pharmaceuticals, Inc.; Transcept Pharmaceuticals, Inc.; University of Michigan, Department of Psychiatry; Usona Institute,Inc.; Vanda Pharmaceuticals, Inc.; Versant Venture Management, LLC; VistaGen; Xenon Pharmaceuticals Inc.; Speaking/Publishing: Adamed, Co; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; AstraZeneca; Belvoir Media Group; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Cephalon, Inc.; CME Institute/Physicians Postgraduate Press, Inc.; Eli Lilly and Company; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Global Medical Education, Inc.; Imedex, LLC; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; Novartis AG; Organon Pharmaceuticals; Pfizer Inc.; PharmaStar; United BioSource,Corp.; Wyeth-Ayerst Laboratories; Equity Holdings: Compellis; Neuromity; Psy Therapeutics; Sensorium Therapeutics; Royalty/patent, other income: Patents for Sequential Parallel Comparison Design (SPCD), licensed by MGH to Pharmaceutical Product Development, LLC (PPD) (US_7840419, US_7647235, US_7983936, US_8145504, US_8145505); and patent application for a combination of Ketamine plus Scopolamine in Major Depressive Disorder (MDD), licensed by MGH to Biohaven. Patents for pharmacogenomics of Depression Treatment with Folate (US_9546401, US_9540691). Copyright: for the MGH Cognitive & Physical Functioning Questionnaire (CPFQ), Sexual Functioning Inventory (SFI), Antidepressant Treatment Response Questionnaire (ATRQ), Discontinuation-Emergent Signs & Symptoms (DESS), Symptoms of Depression Questionnaire (SDQ), and SAFER; Belvoir; Lippincott, Williams & Wilkins; Wolkers Kluwer; World Scientific Publishing Co. Pte. Ltd. CCF: nothing to disclose CC: personal fees from Janssen, Perception, and Takeda; and grants from Clexio, Livanova, AFSP, and the National Institute of Mental Health. MHT: research support from the Agency for Healthcare Research and Quality, Cyberonics Inc., National Alliance for Research in Schizophrenia and Depression, NIMH, National Institute on Drug Abuse, National Institute of Diabetes and Digestive and Kidney Diseases, and Johnson & Johnson; consulting and speaker fees from Abbott Laboratories Inc., Akzo (Organon Pharmaceuticals Inc.), Allergan Sales LLC, Alkermes, Astra Zeneca, Axon Advisors, Brintellix, Bristol-Myers Squibb Company, Cephalon Inc., Cerecor, Eli Lilly & Company, Evotec, Fabre Kramer Pharmaceuticals Inc., Forest Pharmaceuticals, GlaxoSmithKline, Health Research Associates, Johnson & Johnson, Lundbeck, MedAvante Medscape, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America Inc., MSI Methylation Sciences Inc., Nestle Health Science-PamLab Inc., Naurex, Neuronetics, One Carbon Therapeutics Ltd, Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals Inc., Pfizer Inc., PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products Ltd, Sepracor, SHIRE Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/ Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, and Wyeth- Ayerst Laboratories.
Tables 1 to 3 are available in the Supplementary Files section