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Melatonin Treatment for Tardive Dyskinesia
A Double-blind, Placebo-Controlled, Crossover Study
Eyal Shamir, MD;
Yoram Barak, MD;
Irena Shalman, MD;
Moshe Laudon, PhD;
Nava Zisapel, PhD;
Ricardo Tarrasch, MA;
Avner Elizur, MD;
Ronit Weizman, MD
Arch Gen Psychiatry. 2001;58:1049-1052.
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.
From the Abarbanel Mental Health Center, Bat-Yam, Israel (Drs Shamir,
Barak, Shalman, and Elizur); Sackler Faculty of Medicine (Drs Shamir, Barak,
Shalman, Elizur, and Weizman), Department of Neurobiochemistry, Faculty of
Life Sciences (Dr Zisapel), and Department of Psychology (Mr Tarrasch), Tel
Aviv University, Neurim Pharmaceuticals Ltd (Drs Laudon and Zisapel), and
Tel Aviv Mental Health Center (Dr Weizman), Tel Aviv, Israel.
Corresponding author and reprints: Eyal Shamir, MD, Abarbanel Mental
Health Center, 15 KKL St, Bat-Yam 59100, Israel (e-mail: drshamir{at}hotmail.com).
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