Allopurinol as adjunctive treatment for acute mania in hospitalized bipolar patients

Shahin Akhondzadeh, Mehdi Rafiee Milajerdi, Homayoun Amini, Mahdieh Moin, Fattaneh Sadat Bathaei and Abbas Kamlipour

Objective: Mania is frequently associated with behavioral disturbances that can have serious consequences for patients and those in contact with them. Rapid control is important, even though many patients may be uncooperative. For many, the effectiveness of current treatments for acute bipolar mania is suboptimal. It has been reported that the abnormalities observed during mania seem to be associated with some pathophysiologic changes in the purinergic system. Recently, allopurinol, a hypouricemic agent, has been shown to present therapeutic effects in mania associated with hyperuricemia. The objective of this double-blind, placebo-controlled study was to investigate the efficacy and tolerability of allopurinol as an adjunct to lithium and haloperidol for treatment of acute mania in hospitalized bipolar patients. Methods: A total of 82 patients between the ages of 8 to 49 years and who met the Diagnostic and Statistical Manual of Mental Disorders IV criteria for a current manic episode, on the basis of a clinical interview by an academician psychiatrist were eligible for the trial. 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. A total of 41 patients were randomly allocated to lithium in two groups where Group A: (1–1.2mEq/l) + haloperidol (10 mg/day) + allopurinol (300 mg/day) or Group B: lithium (1–1.2 mEq/l) + haloperidol (10 mg/day) + placebo for a 6-week, double-blind, placebo-controlled study. Patients were assessed by a third year resident of psychiatry at baseline and at 7, 14, 28 and 42 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. Extrapyramidal symptoms were assessed using the Extrapyramidal Symptoms Rating Scale. Side effects were systematically recorded throughout the study and 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; d.f. = 1; p = 0.02), thus implying that the mean Extrapyramidal Symptoms Rating Scale 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 a purinergic dysfunction in the disorder.