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


CONCLUSIONS
This is the first clinical evidence for efficacy of melatonin in the treatment of TD.
Shamir
E
E
Abarbanel Mental Health Center, 15 KKL St, Bat-Yam 59100, Israel. drshamir@hotmail.com
Barak
Y
Y
Shalman
I
I
Laudon
M
M
Zisapel
N
N
Tarrasch
R
R
Elizur
A
A
Weizman
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects; D002908:Chronic Disease; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D004298:Dopamine / Q000378:metabolism; D004311:Double-Blind Method; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy
D000975:Antioxidants; D014150:Antipsychotic Agents; D008550:Melatonin; D004298:Dopamine