Allopurinol augmentation in acute mania: A meta-analysis of placebo-controlled trials

Background: Allopurinol is a xanthine oxidase inhibitor commonly used in the treatment of gout. Recent studies have also shown its promise as an adjunctive treatment for manic episodes in bipolar 1 disorder, possibly through mechanisms involving the purinergic pathway. However, its efficacy across studies has been inconsistent, so we conducted a meta-analysis of the published controlled studies with the goal of determining the efficacy profile of allopurinol as an adjunctive treatment for mania in bipolar disorder. Methods: An online search was conducted using PubMed for placebo-controlled, randomized, double-blind, clinical trials (RCTs) using the terms "allopurinol," " bipolar," "mania," "manic," and "YMRS" and a meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. Results: Five studies met the criteria for inclusion. Three of the five studies were inpatient treatments, one study was outpatient treatment, and one study had a mixture of both. All studies used allopurinol as an adjunct in treating acute mania in bipolar disorder subjects. Four of the studies showed efficacy in the primary outcome measure between allopurinol vs. placebo groups with significantly reduced YMRS scores while one showed no significant effect size between the allopurinol and placebo groups. The overall effect size for the four studies is d = 0.294. No significant difference in side effects were found between groups for any of the studies. Conclusion: The data suggest that allopurinol may have some efficacy as an adjunct in reducing mania symptoms during acute manic episodes in patients with bipolar disorder. Adjunctive allopurinol efficacy may be related to the mood stabilizer used. Additional controlled trials with greater sample sizes, homogenous dosing, and consistent treatment modalities are needed to determine optimal clinical application.