Effects of Exogenous Melatonin Administration and Withdrawal
in Five Patients With Rapid-Cycling Bipolar Disorder

Ellen Leibenluft, M.D., Susana Feldman-Naim, M.D., Erick H. Turner, M.D.,
Thomas A. Wehr, M.D., and Norman E. Rosenthal, M.D.

Background: The ready availability of exogenous melatonin means that its use in patients with mood disorders is probably not uncommon. Nonetheless, few controlled trials of exogenous melatonin in these patients have been conducted.

Method: Five patients with rapid-cycling DSM-III-R bipolar disorder were treated with melatonin 10 mg q.d. at 10:00 p.m. for 12 weeks. Melatonin was added to a stable regimen of medication and administered in a double-blind,
placebo-controlled fashion.

Results: Melantonin administration had no positive effects. One patient developed a free-running (unentrained) sleep-wake cycle after melatonin withdrawal. In addition, in both this and a second patient, there is evidence that the administration of exogenous melatonin may have suppressed the secretion of endogenous melatonin.

Conclusion: The administration of melatonin had no significant effects on mood or sleep.
However, melatonin withdrawal delayed sleep onset time and may have had some mild mood-elevating effects.

(J Clin Psychiatry 1997;58:383_388)