Melatonin May Treat Side Effects of Antipsychotics

NEW YORK (Reuters Health) - New study findings suggest that melatonin could
help ease the side effects of drugs used to treat schizophrenia.
These drugs, known as antipsychotics, produce a set of symptoms called
tardive dyskinesia (TD), which include involuntary movements of the limbs and
face, tremors and stiffness. There is currently no treatment for TD.

"To our knowledge, this is the first study to demonstrate clinically
meaningful improvement of TD symptoms with melatonin," study lead author Dr.
Eyal Shamir of Abarbanel Mental Health Center in Israel and his colleagues
write in the November issue of the Archives of General Psychiatry. Melatonin
is a hormone produced by the brain's pineal gland. Because it is released
into the bloodstream at night, the hormone is thought to play a role in
regulating sleep.

Schizophrenia, which affects 1% of the population, usually strikes in young
adulthood, causing disordered thinking and behavior.

With medication, therapy and rehabilitation, many people with schizophrenia
can live relatively normal lives, holding down a job and living
independently, experts agree. Yet the side effects associated with
antipsychotics cause many patients--as many as 40%--to stop taking the drugs,
according to a recent report in The New England Journal of Medicine.

To investigate melatonin as a potential TD treatment, Shamir and colleagues
studied 22 patients with schizophrenia. About half received 10 milligrams of
melatonin daily for 6 weeks, followed by another 6 weeks of treatment with an
inactive placebo drug. The other half were treated with the inactive drug
first, followed by melatonin. All patients had a 4-week "washout period," or
break, between treatments.

Overall, the study participants exhibited less severe symptoms after they
were treated with melatonin in comparison to after they received the inactive
therapy, the investigators report. This finding remained true regardless of
whether the patients were first treated with melatonin or the placebo.

What's more, seven people showed a more than 3-point reduction in TD symptom
severity--a clinically significant improvement. Nine patients had a 30% or
greater improvement in their symptoms after melatonin treatment, the report
indicates.

"It remains to be studied whether the efficacy of melatonin will further
increase with longer treatment or with larger doses of the hormone," the
researchers comment.

The exact mechanism of action for melatonin is not known, but Shamir's team
speculates that it may be related to melatonin's powerful antioxidant
properties, which have been shown to have a protective effect on nerve cells.

In a related editorial, Dr. William M. Glazer of Massachusetts General
Hospital and his colleagues write that melatonin may be suppressing TD
symptoms instead of treating them, based on its proposed mechanism of action.
They further point out that the 30% or more reduction in symptom severity is
"relatively weak," considering the 50% or more reduction in symptom severity
required before a treatment is assumed effective.

"From our perspective, the treatment value of melatonin for TD is
questionable," the editorialists write.

They add, however, that the hormone should not be ignored. "Although the
newer-generation antipsychotic agents may be diminishing the concern about
TD, there remain other safety concerns with these agents that might be helped
with antioxidants and other 'alternative' therapies," Glazer's team concludes.

SOURCE: Archives of General Psychiatry 2001;58:1049-1052, 1054-1055.