Mania associated with antidepressant treatment: comprehensive meta-analytic review

Acta Psychiatr Scand. 2010 Jun;121(6):404-14. doi: 10.1111/j.1600-0447.2009.01514.x. Epub 2009 Dec 2.

Abstract

Objective: To review available data pertaining to risk of mania-hypomania among bipolar (BPD) and major depressive disorder (MDD) patients with vs. without exposure to antidepressant drugs (ADs) and consider effects of mood stabilizers.

Method: Computerized searching yielded 73 reports (109 trials, 114 521 adult patients); 35 were suitable for random effects meta-analysis, and multivariate-regression modeling included all available trials to test for effects of trial design, AD type, and mood-stabilizer use.

Results: The overall risk of mania with/without ADs averaged 12.5%/7.5%. The AD-associated mania was more frequent in BPD than MDD patients, but increased more in MDD cases. Tricyclic antidepressants were riskier than serotonin-reuptake inhibitors (SRIs); data for other types of ADs were inconclusive. Mood stabilizers had minor effects probably confounded by their preferential use in mania-prone patients.

Conclusion: Use of ADs in adults with BPD or MDD was highly prevalent and moderately increased the risk of mania overall, with little protection by mood stabilizers.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Age Factors
  • Antidepressive Agents, Tricyclic / administration & dosage
  • Antidepressive Agents, Tricyclic / adverse effects*
  • Antimanic Agents / therapeutic use*
  • Bipolar Disorder* / chemically induced
  • Bipolar Disorder* / prevention & control
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / physiopathology
  • Depressive Disorder, Major / psychology
  • Humans
  • Lithium / therapeutic use*
  • Middle Aged
  • Models, Statistical
  • Risk Factors
  • Serotonin Uptake Inhibitors / administration & dosage
  • Serotonin Uptake Inhibitors / adverse effects*
  • Time Factors

Substances

  • Antidepressive Agents, Tricyclic
  • Antimanic Agents
  • Serotonin Uptake Inhibitors
  • Lithium