Naltrexone is associated with reduced drinking by alcohol dependent patients receiving antidepressants for mood and anxiety symptoms: Results from VA cooperative study no. 425, "naltrexone in the treatment of alcoholism"

John H. Krystal, Ralitza Gueorguieva, Joyce Cramer, Joseph Collins, Robert Rosenheck, K. Drexler, F. Mohammad, L. Siklosky, K. Walker, C. Arnold-Hunter, R. Head, J. Hermos, H. Behr, B. Kinne, D. Savage, J. Wickis, L. Rugle, O. Kausch, H. Zegarna, K. ContiH. Adkins, G. Harris, C. Cartier, B. Adinoff, L. Burney, J. Fields, B. Hudson, J. Corder, A. Quintero, J. Grabowski, R. Wancha, Y. Ruiz, S. Chermack, S. Fleming, K. Gamel, B. Sullivan, L. Madlock, R. Murray, J. Williams, R. Lewandowski, T. Owens, M. FeBornstein, J. Pena, B. Cotton-Brown, M. Cowie, A. Connelly, W. Hill, A. Holmes, J. Fiery, P. Casadonte, S. Kushner, S. Johnson, J. Siegris, N. Lynch, E. Richardson, A. Butcher, S. Nixon, C. Shaw, R. Joswick, D. Bertoch, H. Engebretson, L. Haynes-Tucker, L. Moffet, J. Weintraub, R. Lutz, S. Clinton, F. Pohlman, R. Royal, S. Harris, I. Maany, J. DeStefano, M. Andem, C. Hackett, J. McNeely, S. Dyanick, D. Torpey, S. Poole, E. Moeller, A. Scheamania, G. Kaplan, H. MacAskill, P. Charnley, C. Williams, C. Stock, P. Stevenson, S. Plumb, M. Dean, J. Hunter, P. Banys, I. Rhew, S. Staccone, J. Kelly, S. Shives, A. Saxon, M. Willey-Allen, J. Williams, K. Lunna, V. Ruscigno, S. Brown, K. Shaffer, J. Collins, S. Kilby, T. Burke, L. Linzy, C. Dalzell, M. Rhoads, J. Kelly, N. Banks, J. Arflin, D. Briones, W. Krol, M. Miller, C. Messick

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20 Scopus citations


Background: It is not clear whether naltrexone is effective in reducing alcohol consumption among patients with clinically significant mood symptoms and whether naltrexone favorably interacts with antidepressant medications when they are co-prescribed. Methods: This study reflects a secondary analysis of the first 13 weeks of VA CSP #425, a study that evaluated the efficacy of naltrexone 50 mg/d in 627 alcohol dependent military veterans receiving Twelve Step Facilitation therapy at 20 VA Medical Centers. This study included patients with comorbid mood and anxiety disorders, providing they did not need treatment for these comorbid conditions at the time of study entry. Sixty patients developed sufficiently severe mood symptoms while on study medication that they required antidepressant treatment. This analysis evaluated whether the efficacy of naltrexone and placebo was influenced by the prescription of antidepressant medications to some study patients for their mood and anxiety symptoms. Results: In patients randomized to placebo (n = 209), prescription of antidepressants was associated with a significantly higher percentage of drinking days (lsmean = 24.4, se = 4.85 vs. lsmean = 12.9, se = 1.69, p = 0.02). Although the group of patients receiving naltrexone (n = 418) was larger than the group assigned to placebo, there were no significant differences in drinking-related outcomes in the groups who did or did not receive antidepressants (lsmean = 11.5, se = 1.18 vs. lsmean = 12.9, se = 1.69, p = 0.47). Among the group of patients receiving antidepressants, naltrexone prescription was associated with a reduction in the percent drinking days compared to placebo [lsmean = 10.1, se = 3.47 vs. lsmean = 24.4, se = 4.85, F(1,556) = 5.84, p = 0.02]. Conclusions: Further investigation will be needed to determine whether naltrexone is efficacious among depressed alcohol dependent patients and whether naltrexone and antidepressant medications show interactive efficacy for treating alcohol dependence.

Original languageEnglish (US)
Pages (from-to)85-91
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Issue number1
StatePublished - Jan 2008


  • Alcohol Dependence
  • Antidepressants
  • Depression
  • Mood Disorder
  • Naltrexone
  • Treatment

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health


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