Objective:  The prevalence, characteristics, and possible risk factors associated with antidepressant‐induced mania remain poorly described. The present review sought to identify published rates of antidepressant‐induced mania and describe risk factors for its emergence.

Methods:  A MedLine search was conducted of journals that focused on mania or hypomania associated with recent antidepressant use. Data from published reports were augmented with relevant findings from recent clinical trials presented at scientific conferences.

Results:  Antidepressant‐induced manias have been reported with all major antidepressant classes in a subgroup of about 20–40% of bipolar patients. Lithium may confer better protection against this outcome when compared with other standard mood stabilizers, although switch rates have been reported with comparable frequencies on or off mood stabilizers. Evidence across studies most consistently supports an elevated risk in patients with (i) previous antidepressant‐induced manias, (ii) a bipolar family history, and (iii) exposure to multiple antidepressant trials.

Conclusion:  About one‐quarter to one‐third of bipolar patients may be inherently susceptible to antidepressant‐induced manias. Bipolar patients with a strong genetic loading for bipolar illness whose initial illness begins in adolescence or young adulthood may be especially at risk. Further efforts are needed to better identify high‐vulnerability subgroups and differentiate illness‐specific from medication‐specific factors in mood destabilization.