Pharmacological interventions for prevention of depression in high risk conditions: Systematic review and meta-analysis

J Affect Disord. 2020 May 15:269:58-69. doi: 10.1016/j.jad.2020.03.024. Epub 2020 Mar 7.


Background: Background Depressive disorders account for almost half of all Disability Adjusted Life Years caused by psychiatric disorders but efficacy of pharmacological interventions to prevent depressive disorders is not known. We aimed to assess efficacy of pharmacological treatments in prevention of depression.

Methods: We searched PubMed, Psych Info, EMBASE, and CINHAL from 1980 to January 2020 and bibliographies of relevant systematic reviews. We selected randomised controlled trials (RCTs) that used a pharmacological intervention to prevent the onset of the new depressive episode in adult population. Study selection, data extraction and reporting was done following PRISMA guidelines. Data were pooled using random-effects meta-analysis.

Results: 28 trials (2745 participants) were included in meta-analysis. Antidepressants (22 studies), Selenium, Hormone Replacement Therapy Omega-3 fatty acids and Melatonin were used to prevent depression, mostly in physical conditions associated with high risk of depression. All pharmacological interventions [pooled Odds Ratios (OR) 0.37 CI (0.25-0.54)], and antidepressants (OR 0.29, 95% CI: 0.18, 0.46) were significantly more effective than placebo in preventing depression. Antidepressants were significantly better than placebo in trials that had low risk of bias (n = 16; OR 0.43 [0.30, 0.60]), in preventing post stroke depression (OR = 0.16, 95% CI: 0.05, 0.55) and depression associated with Hepatitis C (OR = 0.56, 95% CI: 0.31, 1.02). Limitations include small number of studies focussed only on high risk conditions and short follow up in most studies.

Conclusions: Prevention of depression may be possible in patients who have high-risk conditions such as stroke but the strategy requires complete risk and benefits analysis before it can be considered for clinical practice.

Keywords: Depression; Depressive illness; Drugs; Meta-analysis; Pharmacological agents; Prevention.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Antidepressive Agents* / therapeutic use
  • Depression* / prevention & control
  • Humans


  • Antidepressive Agents