Allopurinol as an adjunct to lithium and haloperidol for treatment of patients with acute mania: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE

Allopurinol, a hypouricemic agent, has been shown to present therapeutic effects in mania associated with hyperuricemia. This study assessed the efficacy and safety of risperidone as an adjunctive agent to lithium and haloperidol for the treatment of acute mania in hospitalized bipolar patients.

METHODS

Eighty-two patients aged between 18 and 49 were eligible to participate, as they met the DSM-IV criteria for a current manic episode, on the basis of a clinical interview by two academician psychiatrists. In addition, a score of at least 20 points on the Young Mania Rating Scale was required representing at least a moderate-to-severe mania. Forty-one patients were randomly allocated to lithium (1-1.2 mEq/L) + haloperidol (10 mg/day) + allopurinol (300 mg/day) (group A) or lithium (1-1.2 mEq/L) + haloperidol (10 mg/day) + placebo (group B) for an 8-week, double-blind, placebo-controlled study. Patients were assessed by a third-year resident of psychiatry at baseline and at 7, 14, 28, 42, and 56 days after the medication started. The mean decrease in the Young Mania Rating Scale score from baseline was used as the main outcome measure of response of mania to treatment. The extrapyramidal symptoms were assessed using the Extrapyramidal Symptoms Rating Scale (ESRS). Side effects were systematically recorded throughout the study and were assessed using a checklist.

RESULTS

Young Mania Rating Scale scores improved with allopurinol. The difference between the two protocols was significant as indicated by the effect of the group, the between-subjects factor (F = 5.22, df = 1, p = 0.008). The mean ESRS scores for the placebo group were higher than the allopurinol group. However, the differences were not significant over the trial. The difference between the two groups in the frequency of side effects was not significant except for agitation that was more often in the placebo group.

CONCLUSIONS

The efficacy of allopurinol to obtain a greater improvement in patients with mania seems to support the purinergic dysfunction in mania.