SSRI antidepressants should not be first choice for treating depression with comorbid alcohol use disorders


All mental health professionals are well aware that depression and alcohol misuse frequently go hand in hand. One condition often complicates and affects the outcome of the other.

NICE guidelines recommend treating the alcohol problems first and then after 3-4 weeks of abstinence focus on treating the comorbid mental illness if it’s still present.

This meta-analysis conducted by a team from Harvard Medical School set out to examine the efficacy of antidepressants in patients with unipolar major depressive disorder (MDD) and/or dysthymic disorder with comorbid alcohol use disorders and to compare antidepressant and placebo response rates between depressed patients with or without comorbid alcohol use disorders.

The researchers found 195 randomised, double-blind, placebo-controlled trials to include in their review. All of the trials looked at antidepressant monotherapy versus placebo for acute treatment of depression or dysthymia in patients with or without alcohol use disorders. Eleven of the RCTs focused specifically on patients with comorbid alcohol use disorders.

Here’s what they found:

  • Antidepressants were better than placebo for patients with comorbid alcohol use disorders (risk ratio of response = 1.336; P = .021)
  • Selective serotonin reuptake inhibitor (SSRI) antidepressants when examined alone, were not better then placebo (P > .05)
  • When looking at all of the studies together, there was no significant difference in the relative efficacy of antidepressants versus placebo (P = .973)

The authors conclude:

These results support the utility of certain antidepressants (tricyclics, nefazodone) in treating depression in patients with comorbid alcohol use disorders. More data on the use of newer antidepressants, including the SSRIs, for this select patient population are needed.

This leaves something of a dilemma for mental health professionals as it clearly shows that SSRIs should not be the first choice treatment for people with depression and alcohol use disorders. However, the older tricyclic antidepressants are associated with more cardiotoxic side effects when mixed with alcohol.

New trials that investigate the effectiveness and safety of new antidepressants with mixed serotonergic and noradrenergic activity are now urgently needed.


Iovieno N, Tedeschini E, Bentley KH, Evins AE, Papakostas GI. Antidepressants for major depressive disorder and dysthymic disorder in patients with comorbid alcohol use disorders: a meta-analysis of placebo-controlled randomized trials. J Clin Psychiatry. 2011 Aug;72(8):1144-51. Epub 2011 Apr 19. [PubMed abstract]

NICE depression pathway

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