Olanzapine and clozapine: comparative effects on motor function in hallucinating PD patients

To compare olanzapine and clozapine for safety and efficacy measures of psychosis and motor function in patients with PD and chronic hallucinations.

Hallucinations occur in approximately one third of patients with PD treated chronically with dopaminergic drugs. Although clozapine is known to be an effective antipsychotic agent that does not significantly exacerbate parkinsonism, its use requires frequent blood count assessment. Olanzapine is another novel antipsychotic that is not associated with blood dyscrasia, and if equally effective could become the preferred drug for treating hallucinations in subjects with PD.

A randomized, double-blind, parallel comparison of olanzapine and clozapine in patients with PD with chronic hallucinations was conducted. The primary outcome measure was the Scale for the Assessment of Positive Symptoms (SAPS) for psychotic symptoms. The Unified Parkinson's Disease Rating Scale (UPDRS) motor subscale was used as a secondary outcome measure and as a safety monitoring tool.

After 15 patients had completed the study, safety stopping rules were invoked because of exacerbated parkinsonism in olanzapine-treated subjects. UPDRS motor impairment scores from baseline to study end significantly increased with olanzapine treatment, and change scores between the olanzapine and clozapine groups significantly differed. The primary clinical domains responsible for the motor decline were gait and bradykinesia. Even with a smaller patient number than originally anticipated, clozapine significantly improved hallucinations and overall behavioral assessment, whereas olanzapine had no effect.

At the doses studied, olanzapine aggravates parkinsonism in comparison with clozapine and should not be regularly used in the management of hallucinations in patients with PD.