Melatonin treatment for tardive dyskinesia: a double-blind, placebo-controlled, crossover study

Arch Gen Psychiatry. 2001 Nov;58(11):1049-52. doi: 10.1001/archpsyc.58.11.1049.


Background: Antipsychotics remain the mainstay of drug intervention in the management of schizophrenia. However, long-term treatment with antipsychotics is associated with a variety of movement disorders, the most disabling of which is tardive dyskinesia (TD), which occurs in up to 50% of patients hospitalized with chronic schizophrenia. The pathophysiology of TD is still unclear and no definite treatment exists. Both dopamine receptor supersensitivity and oxidative stress-induced neurotoxicity in the nigrostriatal system are apparently implicated. The pineal hormone melatonin is a potent antioxidant and attenuates dopaminergic activity in the striatum and dopamine release from the hypothalamus. Thus, it may have a beneficial effect for both the treatment and prevention of TD.

Methods: Using a double-blind, placebo-controlled, crossover study, we evaluated the efficacy of 10 mg/d of melatonin for 6 weeks in 22 patients with schizophrenia and TD. The primary outcome measure was the change from baseline in Abnormal Involuntary Movement Scale (AIMS) score.

Results: The decrease (mean +/- SD) in AIMS score was 2.45 +/- 1.92 for the melatonin and 0.77 +/- 1.11 for the placebo treatment groups (P<.001). No adverse events or side effects were noted.

Conclusion: This is the first clinical evidence for efficacy of melatonin in the treatment of TD.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Antipsychotic Agents / adverse effects
  • Chronic Disease
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Cross-Over Studies
  • Dopamine / metabolism
  • Double-Blind Method
  • Dyskinesia, Drug-Induced / etiology
  • Dyskinesia, Drug-Induced / prevention & control*
  • Female
  • Humans
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Male
  • Melatonin / administration & dosage
  • Melatonin / pharmacology
  • Melatonin / therapeutic use*
  • Middle Aged
  • Schizophrenia / drug therapy


  • Antioxidants
  • Antipsychotic Agents
  • Melatonin
  • Dopamine