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From the National Hospital for Neurology and Neurosurgery (Drs. Manson, Schrag, and Lees), Queen Square, London; and the Reta Lila Weston Institute for Neurological Studies (Drs. Manson and Lees), The Middlesex Hospital, London.
Address correspondence and reprint requests to Dr. A.J. Lees, the National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK; e-mail: alees{at}ion.ucl.ac.uk
OBJECTIVE: To assess the usefulness of low-dose olanzapine (2.5 to 7.5 mg/day) for Levodopa-induced-dyskinesias (LID) in patients with PD.
METHODS: Ten patients with PD and LID took part in this randomized, placebo-controlled, double blind, crossover trial. Patients received a 2-week course of olanzapine or placebo in each treatment phase with 1-week washout in between. Dyskinesias were assessed at baseline and after each treatment period with an acute dopaminergic challenge and unified PD rating scale (UPDRS) questionnaires. Patients also kept on/off and dyskinesia diaries for the last 3 days prior to each assessment.
RESULTS: There was a 41% difference in dyskinesia reduction on olanzapine compared to placebo, as measured by objective dyskinesia rating scales (mean percentage reduction abnormal involuntary movement score: 30% versus -11.2%, p < 0.02). Similar differences were demonstrated by patient diaries (mean reduction: 46% versus -2%, p < 0.02) and UPDRS items 32 and 33. Compared with placebo, treatment with olanzapine resulted in significant increases in ‘off’ time as measured by patient diaries (30% versus 2%) and reported adverse events (1.7 versus 0.1) including increased parkinsonism (1.1 versus 0.1) and a nonsignificant reported increase in drowsiness.
CONCLUSIONS: Low-dose olanzapine is effective in reducing dyskinesias in PD, but even at very low doses can result in unacceptable increases in parkinsonism and ‘off’ time.
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