Should Risperidone Be Used in Parkinson's Disease?

SIR: We were interested in the report by Workman et al.¹ on the use of risperidone in patients with Parkinson's disease (PD). Their results are so contrary to our own² and those of other PD specialists³ that we feel the need to present a dissenting opinion.

Workman et al. prospectively evaluated 9 psychiatric patients treated with risperidone who had a diagnosis of PD. They noted improvement in psychiatric function without worsening parkinsonism after a mean of 37 hospital days. They also noted no change in the dose or number of anti-PD medications used.

We note the following problems. No mention was made as to how risperidone was chosen as the antipsychotic. Were all psychotic PD patients put on this drug, or were drug choices made in a special manner? Three patients had been taking “typical” neuroleptics; discontinuation of the antipsychotic should have resulted in improvement in parkinsonism, confounding interpretation of the reported mean score on their measure of parkinsonism of all 9 patients. Four patients had Alzheimer's disease, 1 had PD dementia, and 1 was schizophrenic. How was Alzheimer's distinguished from PD dementia or diffuse Lewy body disease? Were the Alzheimer's patients, who may have had mild parkinsonism due to the Alzheimer's, misdiagnosed on account of typical neuroleptic effects? How was haloperidol/loxapine-exacerbated PD distinguished from pure drug-induced parkinsonism? The authors wrote that “side effects were measured with the RSSE [Rating Scale for Side Effects], which is neither the most sensitive nor the most specific measure of extrapyramidal side effects.” They should have pointed out that the RSSE is an 11-item scale that contains a single item, tremor, that is possibly an extrapyramidal sign.⁴ The other 10 items are not. In short, they did not measure parkinsonism.

Finally, Workman's patients were treated in a manner that most Parkinson's disease specialists would find unsettling. Four were taking anticholinergics and 2 were on selegiline. Two were not on levodopa. (What were they taking?) Yet the anticholinergics and selegiline were not stopped. Why not? This runs counter to the current management approaches,^5,6 which would first stop anticholinergics and selegiline before initiating an antipsychotic.

There is only one other report of risperidone's beneficial effect in PD.⁷ However, this publication involved only 10 subjects and was presumably considered a success despite a 70% dropout rate, because only 2 of the 7 terminators discontinued risperidone as a result of worsened parkinsonism. However, 1 of the 3 who remained on risperidone suffered a minor increase in parkinsonism, offset by a higher dose of anti-PD medications. These disappointing experiences^2,3,7 should prompt consideration of other antipsychotics with fewer parkinsonian side effects.

In our experience risperidone is misclassified. We believe it is not an atypical neuroleptic. It causes increased prolactin secretion, like typical neuroleptics.⁸ It induces every type of extrapyramidal syndrome and, in most cases, worsens motor function in PD patients. In some reports, risperidone has caused side effects equal to or greater than those caused by haloperidol,^9,10 and it blocks the dopamine D₂ receptors equally.¹⁰ We believe risperidone should not be used in PD. Sufficient experience has demonstrated that it worsens PD. Olanzapine may be more benign,¹¹ although it too may exacerbate parkinsonism.^12,13 Quetiapine appears promising,¹⁴ and clozapine has been demonstrated in several hundred PD patients⁶ and one double-blind placebo-controlled trial¹⁵ to improve psychosis without worsening parkinsonism.