Allopurinol as add-on treatment for mania symptoms in bipolar disorder: Systematic review and meta-analysis of randomised controlled trials

Background Since bipolar disorder seems to be associated with purinergic system dysfunction, allopurinol might be effective in treating symptoms of mania. Aims To estimate the efficacy and tolerability of allopurinol as adjunctive treatment for mania symptoms in people with bipolar affective disorder. Method We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effects of adjunctive allopurinol and placebo on mania symptom changes. Results Five RCTs were included in the meta-analysis. Participants with allopurinol augmentation had a significantly greater decrease in mania symptoms than those with placebo (SMD =70.34, P = 0.007), especially in people with the most severe forms of mania. Remission rates, although based on only two studies (n = 177), were significantly higher among individuals receiving allopurinol, whereas for discontinuation and side-effects no difference was found. Conclusions Our finding of a small to moderate effect size and overall low evidence for add-on allopurinol in reducing mania symptoms indicate that its use in routine practice needs further elucidation.