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Letter
Published Online: 1 November 1998

Should Risperidone Be Used in Parkinson's Disease?

Publication: The Journal of Neuropsychiatry and Clinical Neurosciences
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 experiences2,3,7 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.

References

1.
Workman RH Jr, Orengo CA, Bakey AA, et al: The use of risperidone for psychosis and agitation in demented patients with Parkinson's disease. J Neuropsychiatry Clin Neurosci 1997; 9:594–597
2.
Rich S, Friedman JH, Ott BR: Risperidone versus clozapine for the treatment of drug-induced psychosis in Parkinson's patients. J Clin Psychiatry 1995; 56:556–559
3.
Ford B, Lynch T, Greene P: Risperidone and Parkinson's disease. Lancet 1994; 344:681
4.
Åsberg M, Cronholm B, Sjoquist F, et al: Correlation of subjective side effects with plasma concentrations of nortriptyline. British Medical Journal 1970; 4:18–21
5.
Olanow CW, Koller WC: An algorithm (decision tree) for the management of Parkinson's disease: treatment guidelines. Neurology 1998; 50(suppl 3):S41–S47
6.
Factor SA, Molho ES, Podskalny GD, et al: Parkinson's disease: drug-induced psychiatric states, in Behavioral Neurology of Movement Disorders, edited by Weiner WJ, Lang AE (Advances in Neurology, vol 65). New York, Raven, 1995, pp 115–138
7.
Meco G, Allesandri A, Giustini P, et al: Risperidone in levodopa-induced psychosis in advanced Parkinson's disease: an open label long-term study. Mov Disord 1997; 12:610–612
8.
Tran PV, Hamilton SH, Kuntz AJ, et al: Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders. J Clin Psychopharmacol 1997; 17:407–418
9.
Rosebush PI, Mazurek M: Extrapyramidal side-effects of risperidone. Neurology 1997; 48:A325–A326
10.
Knable MB, Heinz A, Raedler T, et al: Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels. Psychiatry Res 1997; 17:407–418
11.
Wolter E, Jansen ENH, Tuynman-Qua HG, et al: Olanzapine in the treatment of dopaminetic psychosis in patients with Parkinson's disease. Neurology 1996; 47:1085–1087
12.
Friedman JH, Goldstein S: Olanzapine in Parkinson's psychosis. Neurology (in press)
13.
Friedman JH, Goldstein S, Jacques C: Changing clozapine to olanzapine in stable PD patients treated for drug-induced psychosis. Clin Neuropharmacol (in press)
14.
Juncos JL, Evatt ML, Denny J. Long-term effect of quetiapine fumarate in parkinsonism complicated by psychosis. Neurology (in press). Presented at 50th American Academy of Neurology, April 1998
15.
Parkinson's Study Group: Low dose clozapine for the treatment of drug-induced psychosis in Parkinson's disease: results of a placebo-controlled double-blind trial. Neurology (in press). Presented at 50th American Academy of Neurology meeting, April 1998

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Go to The Journal of Neuropsychiatry and Clinical Neurosciences
Go to The Journal of Neuropsychiatry and Clinical Neurosciences
The Journal of Neuropsychiatry and Clinical Neurosciences
Pages: 473 - 474
PubMed: 9813797

History

Published online: 1 November 1998
Published in print: November 1998

Authors

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Joseph H. Friedman, M.D.
Brian R. Ott, M.D.
Department of Clinical Neurosciences, Brown University School of Medicine, Providence, RI

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