Clozapine helps reduce severity and duration of dyskinesias in severe Parkinson's disease
Clozapine (Clozaril) reduces the severity and duration of dyskinesias that result from long-term levodopa therapy in patients with Parkinson's disease, a French study shows.
Franck Durif, of the Gabriel Montpied Hospital in Clermont-Ferrand, and
colleagues examined the effects of the atypical antipsychotic agent in
a study of 50 patients with severe Parkinson’s disease.
The researchers point out that the abnormal involuntary movements (dyskinesias)
sometimes associated with changes in a patient’s levodopa regimen
are not always alleviated by increasing the daily dose of levodopa. “The
high daily doses of levodopa required can lead to chaotic dyskinesias
and severe [psychiatric] disorders.”
They add that interventions used to treat these levodopa-induced dyskinesias,
such as amantadine and surgical therapies, are not always appropriate.
In the 10-week, double-blind study, patients at five hospitals in France
were assigned to either clozapine or placebo. The duration and intensity
of dyskinesias were recorded by patients themselves using self-evaluations
of motor performance fluctuations every two weeks. The mean dose of clozapine,
taken once daily in the evening, was 39.4 mg/day.
Compared with placebo, the duration of levodopa-induced dyskinesias reported
by patients treated with clozapine was reduced by approximately two hours
each day.
In terms of adverse effects, no agranulocytosis was observed in the clozapine
group, but three patients (11.5 per cent) developed eosinophilia. This
resolved rapidly after clozapine was withdrawn.
The exact mechanism by which clozapine improves levodopa-induced dyskinesias
remains unclear. However, the researchers suggest that the improvement
seen in patients treated with clozapine could be related to the potency
with which the drug blocks D1 dopamine receptors (Neurology 2004;62:381).
The author of an accompanying editorial (ibid, p349) concludes: “The
use of [clozapine] must still be balanced by awareness of its relatively
high side effect profile, including the rare, but potentially fatal,
complication of agranulocytosis. However, as levodopa-induced dyskinesias
are potentially disabling for so many Parkinson’s
disease patients, this caveat should be considered a precaution, not
a prohibition, for the use of this otherwise useful medication.”
Clozaril is not currently licensed for the treatment of levodopa-induced
dyskinesias. |
The
Pharmaceutical Journal