Antidepressant pretreatment for the prevention of interferon alfa-associated depression: a systematic review and meta-analysis

Psychosomatics. May-Jun 2014;55(3):221-34. doi: 10.1016/j.psym.2013.06.015. Epub 2013 Sep 5.


Background: Depression is a major complication during treatment with interferon alfa (IFN-α).

Aim: The aim of this study was to clarify whether preemptive antidepressant treatment can reduce the incidence and severity of IFN-associated depression.

Method: Based on a systematic review of the literature up to July 2012, a meta-analysis of the data from 8 trials investigating patients with malignant melanoma or hepatitis C was performed. The influence of antidepressants on the incidence of major depression and depression severity was defined as the primary outcome and the influence of somatic disorder, psychiatric comorbidity, type of antidepressants, type of IFN, and possible effects on treatment outcome as secondary outcome criteria.

Results: Antidepressant pretreatment reduced the overall incidence of major depression during IFN treatment in all patients (odds ratio = 0.42; 95% confidence interval, 0.26-0.68; p < 0.001, n = 589) and was associated with lower mean depression scores after 12 weeks of IFN treatment (g = -0.37; 95% confidence interval -0.59 to -0.18; p < 0.001, n = 375). For patients with hepatitis C virus infection, antidepressants reduced the incidence of major depression (odds ratio = 0.38; 95% confidence interval 0.22-0.66; p < 0.001, n = 549) and the mean depression scores after 24 weeks of IFN treatment (g = -0.50; 95% confidence interval -0.70 to -0.29; p < 0.001, n = 335). The effects of selective serotonin reuptake inhibitors on the incidence and severity of depression were not dependent on pre-existing psychiatric disorders.

Conclusion: Antidepressant pretreatment with selective serotonin reuptake inhibitors lowers the incidence and severity of IFN-associated depression in patients with chronic hepatitis C infection or malignant melanoma.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antidepressive Agents / therapeutic use*
  • Antiviral Agents / adverse effects*
  • Chemoprevention
  • Depressive Disorder / chemically induced
  • Depressive Disorder / prevention & control
  • Depressive Disorder, Major / chemically induced
  • Depressive Disorder, Major / prevention & control*
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon-alpha / adverse effects*
  • Melanoma / drug therapy*
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Treatment Outcome


  • Antidepressive Agents
  • Antiviral Agents
  • Interferon-alpha
  • Serotonin Uptake Inhibitors