Objective: Extrapyramidal disorders are common adverse effects of all antipsychotic treatment, regardless of disease state. Resulting morbidity and mortality from difficulty swallowing and falls are more common in the elderly. Patients treated with conventional agents show a higher incidence and severity than those taking atypical agents; differences between atypicals such as olanzapine (OLZ) and risperidone (RIS) have been less studied, warranting further investigation.
Design: We evaluated acute phases of Lilly-sponsored clinical trials comparing OLZ and RIS, selecting 3 trials with large enrollment and duration 8-10 weeks.
Materials and Methods: Mean ages were 39.1 ± 8.1, 78.3 ± 7.3, and 36.2 ± 10.7 for Studies 1, 2, and 3, respectively. Other comparators were haloperidol (HAL) in Study 1, and placebo in Study 2. Medications were flexibly dosed over the specified therapeutic ranges. We analyzed data from the Simpson-Angus Scale (SAS) and the Barnes Akathisia Scale (BAS) using mixed model repeated measures to compare extrapyramidal symptom (EPS) levels within and between groups over time and study populations.
Results: In all 3 studies, patients taking OLZ experienced less parkinsonism than did patients taking RIS, differentiating by Week 1 in Study 3 (p<.05) and Week 4 in Studies 1 and 2 (p<.05). For either therapy, parkinsonism improved compared to baseline in Studies 1 and 3, but worsened in Study 2. Placebo patients showed no change in levels of EPS over the course of Study 2. In Study 1, the OLZ group improved significantly more than the HAL group at each post-baseline visit except week 8, while RIS failed to separate from HAL at any time. BAS scores only inconsistently favored OLZ over RIS. A meta-analysis of all 3 studies found that while levels of EPS differed across studies, treatment differences, both overall and within levels of visit week, did not depend on study population.
Conclusion:We observed less parkinsonism on OLZ compared to RIS across disease state, dosing ranges, and age demographics, suggesting a lower risk of this serious side effect with OLZ compared to RIS. This study confirmed lower EPS scores when treating with OLZ instead of a conventional antipsychotic (HAL), but did not find differences between RIS and HAL.
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