Title: Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study
Authors: Vanina Popova, M.D., Ella J. Daly, M.D., Madhukar Trivedi, M.D., Kimberly Cooper, M.S., Rosanne Lane, M.A.S., Pilar Lim, Ph.D., Christine Mazzucco, M.Sc., David Hough, M.D., Michael E. Thase, M.D., Richard C. Shelton, M.D., Patricio Molero, M.D., Ph.D., Eduard Vieta, M.D., Ph.D., Malek Bajbouj, M.D., Husseini Manji, M.D., Wayne C. Drevets, M.D., Jaskaran B. Singh, M.D.
Affiliations: Janssen Research and Development, Beerse, Belgium (V.P.), Titusville, N.J. (E.J.D., R.L., P.L., D.H., H.M., W.C.D.), Spring House, Pa. (K.C.), and San Diego (J.B.S.); University of Texas Southwestern Medical Center, Dallas (M.T.); Janssen Inc. Canada, Toronto (C.M.); Perelman School of Medicine, University of Pennsylvania, Philadelphia (M.E.T.); University of Alabama School of Medicine, Birmingham (R.C.S.); Clinica Universidad de Navarra, Pamplona, Spain (P.M.); Institute of Neuroscience, University of Barcelona, Barcelona, Spain (E.V.); Charité Universitätsmedizin Berlin, Berlin (M.B.).
Disclosures: Dr. Popova, Dr. Daly, Ms. Cooper, Ms. Lane, Dr. Lim, Ms. Mazzucco, Dr. Hough, Dr. Manji, Dr. Drevets, and Dr. Singh are employees of Janssen Research and Development and hold company equity. Dr. Trivedi has consulted for or served on advisory boards of AcademyHealth, Acadia Pharmaceuticals, Akili Interactive, Alkermes, Allergan Pharmaceuticals, Avanir Pharmaceuticals, Axsome Therapeutics, Boehringer Ingelheim, Brintellix Global, Bristol-Myers Squibb, Caudex, Cerecor, Forest Pharmaceuticals, Global Medical Education, Health Research Associates, Insys, Janssen Pharmaceutical, Jazz Pharmaceutical, Johnson & Johnson Pharmaceutical Research and Development, Lilly Research Laboratories, Lundbeck Research USA, Medscape, Merck, Mitsubishi Pharma, MSI Methylation Sciences, Navitor, One Carbon Therapeutics, Otsuka America Pharmaceutical, Oxford Pharmagenesis, Pamlab, Pfizer, Sage Therapeutics, and Takeda Global Research; he has received royalties from Janssen Research and Development; he has received research support from the Agency for Healthcare Research and Quality, the Cancer Prevention and Research Institute of Texas, Janssen Research and Development, Johnson & Johnson, the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, NIDA, NIMH, and the Patient-Centered Outcomes Research Institute; he has author agreements from Janssen Asia Pacific and Oxford University Press; and he has received editorial compensation from Engage Health Media, Healthcare Global Village, and Oxford University Press. Dr. Thase has served as a consultant or independent contractor to Acadia, Akili, Alkermes, Allergan (Forest, Naurex), AstraZeneca, Axsome, Cerecor, Eli Lilly, Fabre-Kramer, Gerson Lehrman Group, Guidepoint Global, Lundbeck, Johnson & Johnson, MedAvante, Merck, Moksha8, Nestlé (Pamlab), Neuralstem, Novartis, Otsuka, Pfizer, Shire, Sage, Sunovion, and Takeda; he has received grant or research support from Acadia, the Agency for Healthcare Research and Quality, Alkermes, Allergan (Forest), AssureRx Health, Avanir, Axsome, Intracellular, Janssen Pharmaceuticals, Johnson & Johnson (including for the present study), NIMH, Otsuka, the Patient-Centered Outcomes Research Institute, and Takeda; he has received royalties from the American Psychiatric Foundation, Guilford Publications, Herald House, and W.W. Norton & Company; his spouse is employed by Peloton Advantage, which does business with a number of pharmaceutical companies. Dr. Shelton has served as a consultant to Acadia Pharmaceuticals, Allergan, Cerecor, Janssen Pharmaceutica, MSI Methylation Sciences, Naurex, and Takeda Pharmaceuticals; he has received grant support from Acadia Pharmaceuticals, the Agency for Healthcare Research and Quality, Alkermes, Allergan, Avanir Pharmaceuticals, Cerecor, Genomind, Intracellular Therapies, Janssen Pharmaceutica, Myriad Genetics, Navitor Pharmaceuticals, NeuroRx, NIMH, Novartis, Otsuka Pharmaceuticals, the Patient-Centered Outcomes Research Institute, Sage Therapeutics, and Takeda Pharmaceuticals. Dr. Molero is supported by Clínica Universidad de Navarra and has received research grants from the Ministry of Education (Spain), the Government of Navarra (Spain), the Spanish Foundation of Psychiatry and Mental Health, and AstraZeneca; he is a clinical consultant for MedAvante-ProPhase and has received lecture honoraria from or has been a consultant for AB-Biotics, Janssen, Novumed, Roland Berger, and Scienta. Dr. Vieta has received grants from and/or served as consultant, adviser, or CME speaker for AB-Biotics, Allergan, Angelini, AstraZeneca, the Brain and Behavior Foundation, Bristol-Myers Squibb, Dainippon Sumitomo, Farmindustria, Ferrer, Forest Research Institute, Gedeon Richter, the Generalitat de Catalunya (2014 SGR 398), GlaxoSmithKline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, Sage, Sanofi-Aventis, Servier, the Seventh European Framework Programme (ENBREC), Shire, the Spanish Ministry of Science and Innovation, the Stanley Medical Research Institute, Sunovion, and Takeda. Dr. Bajbouj has received research grants from the Deutsche Forschungsgemeinschaft, the German Federal Ministry for Education and Research, and the Germany Ministry of Health; he has served as a consultant on or advisory boards for Parexel, Janssen, and Johnson & Johnson; and he has received lecture support from Servier. Dr. Manji is named on a patent, which is assigned to Icahn School of Medicine at Mount Sinai, Yale University, and NIH; no financial benefit was received from this patent.
Discussion of unapproved or investigational use of products*: No.
*APA policy requires disclosure by CME authors of unapproved or investigational use of products discussed in CME programs. Off-label use of medications by individual physicians is permitted and common. Decisions about off-label use can be guided by scientific literature and clinical experience.
Ned H. Kalin, M.D. (Editor-in-Chief, AJP); Carolyn Rodriguez, M.D., Ph.D. (Deputy Editor, AJP); Michael D. Roy (Editorial Director, AJP); Michael A. Pogachar (Online Content Manager, Journals). Dr. Kalin has served as a consultant to the Board of Scientific Advisors, the Pritzker Neuropsychiatric Disorders Research Consortium, and the Skyland Trail Advisory Board and as Councilor, Society of Biological Psychiatry. Dr. Rodriguez has served as a consultant to Allergan, Blackthorn, Epiodyne, and Rugen. Mr. Roy and Mr. Pogachar report no financial relationships with commercial interests.