Olanzapine and clozapine - Comparative effects on motor function in hallucinating PD patients

Objective: To compare olanzapine and clozapine for safety and efficacy meas ures of psychosis and motor function in patients with PD and chronic halluc inations. Background: Hallucinations occur in approximately one third of pa tients with PD treated chronically with dopaminergic drugs. Although clozap ine is known to be an effective antipsychotic agent that does not significa ntly exacerbate parkinsonism, its use requires frequent blood count assessm ent. Olanzapine is another novel antipsychotic that is not associated with blood dyscrasia, and if equally effective could become the preferred drug f or treating hallucinations in subjects with PD. Methods: A randomized, doub le-blind, parallel comparison of olanzapine and clozapine in patients with PD with chronic hallucinations was conducted. The primary outcome measure w as the Scale for the Assessment of Positive Symptoms (SAPS) for psychotic s ymptoms. The Unified Parkinson's Disease Rating Scale (UPDRS) motor subscal e was used as a secondary outcome measure and as a safety monitoring tool. Results: After 15 patients had completed the study, safety stopping rules w ere invoked because of exacerbated parkinsonism in olanzapine-treated subje cts. UPDRS motor impairment scores from baseline to study end significantly increased with olanzapine treatment, and change scores between the olanzap ine and clozapine groups significantly differed. The primary clinical domai ns responsible for the motor decline were gait and bradykinesia. Even with a smaller patient number than originally anticipated, clozapine significant ly improved hallucinations and overall behavioral assessment whereas olanza pine had no effect. Conclusions: At the doses studied, olanzapine aggravate s parkinsonism in comparison with clozapine and should not be regularly use d in the management of hallucinations in patients with PD.