Dopaminergic agents in the treatment of bipolar depression: a systematic review and meta-analysis

Objective: To systematically examine the effects of dopaminergic agents (modafinil, armodafinil, pramipexole, methylphenidate, and amphetamines) on bipolar depression outcomes. Methods: Meta-analysis of randomized controlled trials was performed to assess the efficacy and safety of treatment with dopaminergic agents in bipolar depression. In a secondary analysis, findings from both randomized controlled trials and high-quality observational studies were pooled by means of meta-analytic procedures to explore dopaminergic treatment-related new mania. Results: Nine studies (1716 patients) were included in our meta-analysis of randomized controlled trials. Treatment with dopaminergic agents for bipolar depression was associated with an increase in both response (1671 individuals, RR 1.25, 95% CI 1.05 to 1.50) and remission rates (1671 individuals, RR 1.40, 95% CI 1.14, 1.71). There was no evidence of an increased risk of mood switch associated with this treatment (1646 individuals, RR 0.96, 95% CI 0.49, 1.89). Our secondary analysis (1231 individuals) yielded a cumulative incidence of mood switch of 3% (95% CI 1.0, 5.0) during a mean follow-up period of 7.5 months. Conclusions: Preliminary findings suggest that dopaminergic agents may represent a useful alternative for the treatment of bipolar depression, with no evidence for a related increase in the risk of mood destabilization during short-term follow-up.