Abstract
The wars in Iraq and Afghanistan are associated with high rates of post-traumatic stress disorder (PTSD) and comorbid alcohol use disorders. The pharmacotherapy of these comorbid conditions has received relatively little study. The current study compared the serotonin uptake inhibitor, paroxetine, to the norepinephrine uptake inhibitor, desipramine. It also evaluated the adjunctive efficacy of the Food and Drug Administration (FDA)-approved alcoholism pharmacotherapy, naltrexone, relative to placebo. Four groups of predominately male veterans (n=88) meeting current diagnostic criteria for both alcohol dependence (AD) and PTSD were randomly assigned under double-blind conditions to one of four groups: paroxetine+naltrexone; paroxetine+placebo; desipramine+naltrexone; desipramine+placebo. Main outcome measures included standardized scales that assessed symptoms of PTSD and alcohol consumption. Paroxetine did not show statistical superiority to desipramine for the treatment of PTSD symptoms. However, desipramine was superior to paroxetine with respect to study retention and alcohol use outcomes. Naltrexone reduced alcohol craving relative to placebo, but it conferred no advantage on drinking use outcomes. Although the serotonin uptake inhibitors are the only FDA-approved medications for the treatment of PTSD, the current study suggests that norepinephrine uptake inhibitors may present clinical advantages when treating male veterans with PTSD and AD. However, naltrexone did not show evidence of efficacy in this population. This study was registered with ClinicalTrials.gov, registration number NCT00338962 and URL: http://clinicaltrials.gov/ct2/show/NCT00338962?term=desipramine+AND+alcohol+dependence+AND+depression&recr=Closed&rank=1.
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Acknowledgements
This study was conducted with the invaluable help of the VA VISN I MIRECC Study Group: Department of Psychiatry, Bedford VAMC: Marylee Losardo, MSPA, Barbara E Rofman, RN, MS; Department of Psychology, Bedford VAMC: Charles E Drebing, PhD; Department of Psychiatry, VA CT Healthcare, West Haven Campus: Kathryn Keegan, RN, Diana Limoncelli, BA, Colette McHugh-Strong, JD, Alison Oville, BA, Christine Sicignano, BA, J Serrita Jane, PhD, Erin O’Brien, PsyD. Support was provided by VISN I Mental Illness Research Education and Clinical Center (MIRECC; PI, Rounsaville), the VA Alcohol Center (PI, Krystal), and Clinical Neuroscience Division of the VA National Center for PTSD (PI, Krystal).
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Dr Ismene L Petrakis, Dr Elizabeth Ralevski, Dr Nitigna Desai, Dr Louis Trevisan, and Dr Ralitza Gueorguieva declare no conflict of interest. Dr John H Krystal (during the period 2008–2011) has served as a scientific consultant to the following companies (The Individual Consultant Agreements listed below are less than $10 000 per year): Aisling Capital, LLC AstraZeneca Pharmaceuticals, Biocortech, Brintnall & Nicolini, Easton Associates, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Lundbeck Research USA, Medivation, Merz Pharmaceuticals, MK Medical Communications, F Hoffmann-La Roche, SK Holdings, Sunovion Pharmaceuticals, Takeda Industries, Teva Pharmaceutical Industries. He is on the Scientific Advisory Board for the following companies: Abbott Laboratories, Bristol-Myers Squibb, Eisai, Eli Lilly, Forest Laboratories, Lohocla Research Corporation, Mnemosyne Pharmaceuticals, Naurex, Pfizer Pharmaceuticals, Shire Pharmaceuticals. He holds less than $150 in exercisable warrant options with Tetragenex Pharmaceuticals. He is on the Board of Directors: Coalition for Translational Research in Alcohol and Substance Use Disorders. He is President Elect: American College of Neuropsychopharmacology. He is the principal investigator of a multicenter study in which Janssen Research Foundation has provided drug and some support to the Department of Veterans Affairs. He is on the Editorial Board, Editor of Biological Psychiatry (Income Greater than $10 000). He has Patents and Inventions: 1) Seibyl JP, Krystal JH, Charney DS. Dopamine and noradrenergic reuptake inhibitors in treatment of schizophrenia. Patent number: 5 447 948, 5 September 1995; I am a co-inventor with Dr Gerard Sanacora on a filed patent application by Yale University related to targeting the glutamatergic system for the treatment of neuropsychiatric disorders (PCTWO06108055A1). Intranasal Administration of Ketamine to Treat Depression (pending).
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Petrakis, I., Ralevski, E., Desai, N. et al. Noradrenergic vs Serotonergic Antidepressant with or without Naltrexone for Veterans with PTSD and Comorbid Alcohol Dependence. Neuropsychopharmacol 37, 996–1004 (2012). https://doi.org/10.1038/npp.2011.283
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DOI: https://doi.org/10.1038/npp.2011.283
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