Relief from levodopa's herky-jerky movements

The schizophrenia drug clozapine helps reduce dyskinesias in Parkinson's patients. Half better is better than not better at all

By S H Cyr

Levodopa remains the standard treatment for Parkinson's disease, yet the side effects of the drug can sometimes mirror the symptoms of the disease itself. Eventually, sustained levodopa use can produce involuntary, jerky movements, or dyskinesias, in patients. It's one of the most common forms of drug-induced movement disorder.

A French trial suggests that dyskinesias associated with long-term levodopa in severe cases of Parkinson's disease, may be amenable to treatment with the drug clozapine, normally used to treat schizophrenia. The research is published in the February 10 issue of Neurology.

"Dyskinesias are normally very difficult to treat and pose a serious side effect of levodopa therapy, the most common treatment for Parkinson's patients," says lead study author Franck Durif, of the Hôpital Gabriel Montpied in Clermont-Ferrand. "Our study supports previous preliminary findings that low dose clozapine can reduce dyskinesias by around 50% in some patients."

Fifty patients participated in the 10-week, double-blind clinical trial performed at five hospitals in France. The patients performed self-evaluations of their motor performance fluctuations, every two weeks, by means of a diary where they noted duration and intensity of dyskinesias. An acute levodopa challenge was also performed at the beginning and end of the study.

The principal measure of success was the amount of 'on' time during which patients experienced levodopa-induced dyskinesias during waking hours. The clozapine group went from an average of 5.68 hours per day of 'on' time at the study's outset to 3.98 hours on day 70. The placebo group actually worsened, from 4.54 hours on day zero to 5.28 hours on day 70. The total absence of a placebo effect meant that the partial improvement seen with clozapine was enough to achieve the generally accepted level of statistical significance.

Five clozapine patients and seven placebo patients withdrew from treatment. Of the five clozapine patients, three had developed eosinophilia, which rapidly resolved after withdrawal of the drug.

Levodopa-induced dyskinesias are thought to result from increased transmission of dopamine in the brain. Clozapine may be able to mitigate the transmission of toxically high levels of levodopa and lessen the severity and duration of dyskinesias, according to Dr Durif. "Overstimulation of D1 dopaminergic receptors is believed to be one of the most important mechanisms underlying levodopa-induced dyskinesias in Parkinson's disease," he says.

Oddly, clozapine when given for schizophrenia can sometimes cause dyskinesias, though this side effect is much rarer with clozapine than with older antipsychotics.