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Research Summary

Treatment with SSRIs May Improve Depression in Patients with Substance Abuse Disorders

There is a high prevalence of comorbid depression and substance use disorders (SUDs), yet optimal depression treatment and response rates are not well-defined. This observational subgroup analysis of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial compared the treatment efficacy of 12 weeks of citalopram for major depressive disorder (MDD) among patients with and without SUDs. Eligible participants (those with inadequate prior response to depression treatment) were recruited from primary-care and psychiatric sites. Approximately 29% of the 2876 participants had SUDs (19% had an alcohol-use disorder, 5.5% had a drug-use disorder, and 5% had both disorders).

  • Self-reported rates of remission were similar among participants with MDD only (33%) and those with a comorbid alcohol or drug use disorder (36% and 28%, respectively), but lower among participants with both SUDs (22.5%) (p=0.02). Time to remission was also longer in participants with both SUDs than in those with MDD only.
  • Participants with SUDs were more likely to have a serious psychiatric event (5% of participants with 2 SUDS, 4.5% with drug use, 2.4% with alcohol use, and 1% with no SUD [p=0.002]) or to be hospitalized for psychiatric reasons (5.1% with 2 SUDS, 3.2% with drug use, 2.1% with alcohol use, and 1.2% with no SUD [p=0.001]).
  • Three deaths occurred (none by suicide) among participants with SUDs, while none occurred among those with MDD only (p=0.02).


Although patients with SUDs respond to MDD treatment with SSRIs, those with both alcohol and drug use disorders may have a lower and slower response than those with only 1 SUD. Patients with SUDs were more likely to have psychiatric events or hospitalizations. However, since this study was a retrospective observational subgroup analysis and did not include a comparison arm, these results should be considered preliminary for this complex population. Hillary Kunins, MD, MPH, MS


Davis LL, Wisniewski SR, Howland RH, et al. Does comorbid substance use disorder impair recovery from major depression with SSRI treatment? An analysis of the STAR*D level one treatment outcomes. Drug Alcohol Depend. 2010;107(2–3):161–70.