Objective: To determine whether concurrent posttraumatic stress disorder (PTSD) should affect whether to augment or switch medications when major depressive disorder (MDD) has not responded to a prior antidepressant trial. Methods: Patients at 35 Veterans Health Administration medical centers from December 2012 to May 2015 with nonpsychotic MDD (N = 1,522) and a suboptimal response to adequate antidepressant treatment were randomly assigned to 3 “next step” treatments: switching to bupropion, augmenting the current antidepressant with bupropion, and augmenting with the antipsychotic aripiprazole. Blinded ratings with the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C16) determined remission and response by 12 weeks and relapse after remission. Survival analyses compared treatment effects in patients with concurrent PTSD diagnosed with the Mini-International Neuropsychiatric Interview (n = 717, 47.1%) and those without PTSD (n = 805, 52.9%). Results: Patients diagnosed with PTSD showed more severe depressive symptoms at baseline and were less likely to achieve either remission or response by 12 weeks. Augmentation with aripiprazole was associated with greater likelihood of achieving response (68.4%) than switching to bupropion (57.7%) in patients with PTSD (relative risk [RR] = 1.26; 95% CI, 1.01-1.59) as well as in patients without PTSD (RR = 1.29; 95% CI, 1.05-1.97) (78.9% response with aripiprazole augmentation vs 66.9% with switching to bupropion). Treatment comparisons with the group receiving augmentation with bupropion were not significant. There was no significant interaction between treatment group and PTSD on remission (P=.70), response (P=.98), or relapse (P=.15). Conclusions: Although PTSD was associated with poorer overall outcomes, the presence of concurrent PTSD among Veterans in this trial did not affect the comparative effectiveness of medications on response, remission, or relapse after initial remission.
|Journal||Journal of Clinical Psychiatry|
|State||Published - Aug 2020|
Bibliographical noteFunding Information:
Submitted: August 5, 2019; accepted January 2, 2020. Published online: June 23, 2020. Author contributions: Mr Johnson and Dr Sevilimedu had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All information and materials in the article are original. Potential conflicts of interest: Mr Johnson reports his spouse was an employee of and owns stock in Bristol-Myers Squibb. Dr Rao is on the speaker’s bureau of Janssen, Alkermes, Sunovion, and Otsuka-America and has consulted for Janssen and Alkermes. Dr Davis has been a consultant for Tonix, Otsuka, Lundbeck, and Janssen and has done funded research for Tonix, Otsuka, and Alkermes. Dr Thase reports no conflicts of interest specifically related to this research; prior to 2011, he was a consultant and speaker for and received research support from Bristol-Myers Squibb (aripiprazole) and GlaxoSmithKline (bupropion); in the past 3 years, he reports being an advisory/consultant for Acadia, Akili, Alkermes, Allergan (Forest, Naurex), Boehringer-Ingelheim, Clexio Biosciences, H. Lundbeck, Jazz, Janssen (Johnson & Johnson), Otsuka, Perception Neuroscience, Sage, Seelos and Takeda; has received grant support from Acadia, Allergan (Forest, Naurex), Axsome, Intra-Cellular, Johnson & Johnson (Janssen), Otsuka, and Takeda; has received royalties from American Psychiatric Press Incorporated, Guilford Publications, Herald House, and W. W. Norton & Company, Inc; and reports that his spouse is employed by Peloton Advantage, which does business with a number of pharmaceutical companies. Dr Zisook has consulted to Defender Pharmaceuticals and receives research support from COMPASS Pathways. Drs Mohamed, Sevilimedu, Hicks, Chen, Lauro, Jurjus, Pilkinton, Wilcox, Iranmanesh, Sapra, Aslam, and Michalets all report no conflicts of interest. Funding/support: This study was supported by the Cooperative Studies Program, Department of Veterans Affairs, Office of Research and Development. Bristol Myers Squibb provided aripiprazole (Abilify) for use in this study. Role of the sponsor: The Cooperative Studies Program, Department of Veterans Affairs, Office of Research and Development participated in the design and oversaw the conduct of the study including data collection and management and analysis. Disclaimer: Opinions expressed herein are those of the individual authors and the contents do not represent views of the Department of Veterans Affairs or the United States Government. Supplementary material: Available at PSYCHIATRIST.COM.
This study was supported by the Cooperative Studies Program, Department of Veterans Affairs, Office of Research and Development. Bristol Myers Squibb provided aripiprazole (Abilify) for use in this study.
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ASJC Scopus subject areas
- Psychiatry and Mental health