Olanzapine Shows Promise in Treating Psychosis in Parkinson Patients
ABSTRACT & COMMENTARY
Source: Wolters E Ch, et al. Olanzapine in the treatment of dopaminomimetic psychosis in patients with Parkinson's disease. Neurology 1996;47:1085-1087.
Psychosis resulting from dopaminergic therapy for Parkinson's Disease (PD) may be effectively treated using the novel neuroleptic olanzapine (Zyprexa, Eli Lilly), according to a small open-label study carried out by clinical researchers at the Free University in The Netherlands. Olanzapine is the latest of the novel neuroleptics to be approved by the FDA for use in the management of psychotic disorders. It has combined effects on dopaminergic and serotonin type-2 receptors but does not produce granulocytopenia, as do related compounds such as clozapine.
Wolters and colleagues prescribed olanzapine to 15 PD patients without dementia presenting with symptoms of psychosis in the context of receiving one or more standard antiparkinsonian medications (levodopa, pergolide, or bromocriptine). Dose reduction of dopaminergic agents preceded neuroleptic administration, but once olanzapine titration was completed, patients were rechallenged 7-8 weeks later with dopaminomimetic agents to improve their motor symptoms. Responses were evaluated in terms of remission of psychosis and severity of parkinsonism at doses of olanzapine of ranging from 1 to 15 mg/d (mean, 6.5 mg/d) in a single dosing. One patient died during the trial of unrelated causes, but in the 14 other cases, significant reduction in hallucinations, delusions, paranoia, and other symptoms of psychosis was observed 2-5 weeks after initiating olanzapine. No significant neuroleptic-related exacerbation of parkinsonism was observed, and all but one patient treated with olanzapine was able to tolerate reinstitution of antiparkinsonian medications without the return of psychotic symptoms. Two patients who had been treated previously with clozapine without response showed improvement on olanzapine. The total sleep time of these patients increased significantly during olanzapine treatment, but no other significant side effects were observed. The authors conclude that olanzapine may be useful for treating drug-induced psychosis in non-demented PD patients.
COMMENTARY
While conventional neuroleptics tend to exacerbate parkinsonian symptoms in direct relation to their potency, the newer class of neuroleptics such as clozapine have comparable anti-psychotic activity with fewer extrapyramidal side effects. However, clozapine causes leukopenia in some patients and, as a consequence, has not been widely prescribed by neurologists for the treatment of drug-induced psychosis. Although the use of risperidone has not been associated with frequent hematologic complications, it may be more prone than clozapine to cause extrapyramidal side effects. Olanzapine appears to have comparable neuroleptic potency to risperidone and clozapine, but neither precipitates granulocytopenia nor worsens the symptoms of PD. If its effectiveness in treating psychosis in PD patients is verified in larger, double-blind studies, olanzapine could become the drug of choice for treatment of drug-induced psychosis in PD patients.
Patients with dementia were excluded from this study to simplify its interpretation. However, disease-related and drug-induced psychosis are more common in demented PD patients. Olanzapine has some anticholinergic properties that could, in theory, effect cognition in dementia patients, and further studies will be required to assess the safety of this agent in such patients. Currently, olanzapine is approved by the FDA for use in the management of psychotic disorders, based largely on trials for the treatment of schizophrenia. This small, open-label study indicates that olanzapine has promise for future use in the management of dopaminomimetic psychosis in PD patients.
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