Is melatonin treatment effective for tardive dyskinesia?

Tardive dyskinesia is a severe and disabling side effect of conventional antipsychotic treatment, with incidence rates reaching a high of 50% in chronically institutionalized populations. On the basis of recent studies showing some benefit of antioxidants, we evaluated the effect of melatonin, the most potent naturally occurring antioxidant, on tardive dyskinesia in patients with chronic schizophrenia.

Nineteen patients (8 men, 11 women), aged a mean +/- SD 74.0+/-9.5 years with chronic DSM-IV schizophrenia of 31.3+/-7.0 years' duration, were randomly assigned in a double-blind, placebo-controlled, crossover trial to receive slow-release melatonin, 2 mg/day, or placebo for 4 weeks. After a 2-week washout period, the patients were switched to the other treatment arm for an additional 4 weeks. The Abnormal Involuntary Movement Scale (AIMS) was administered at baseline, 4 weeks, 6 weeks, and 10 weeks. Regular administration of antipsychotic and other medications was kept unchanged throughout the study.

Mean AIMS scores did not change significantly from baseline in either treatment arm. All patients completed the study, and there were no side effects or adverse events.

Supraphysiologic doses of melatonin do not positively affect tardive dyskinesia. Considering that melatonin is a safe drug, further studies are needed of higher doses and in patients with shorter disease duration before its use in the treatment of tardive dyskinesia is ruled out.