The Comparative Peripheral Anticholinergic-Like Adverse Event Profiles of Olanzapine and Risperidone

Objective: To test the hypothesis that reported in vitro muscarinic receptor affinity differences between olanzapine and risperidone would be reflected in peripheral solicited anticholinergic adverse event frequencies.

Method: Data from a double-blind, randomized trial of olanzapine versus risperidone in 339 patients (age range, 18-65 years) with DSM-IV schizophrenia spectrum acute psychosis were retrospectively analyzed. Subgroups based on the median of the mean daily drug dose were constructed (olanzapine 17 mg; risperidone 6 mg). Mean daily dose of adjunctive anticholinergic medication was compared using ANOVA, and frequencies of treatment-emergent solicited adverse events defined by the Association de Méthodologie et de Documentation en Psychiatrie (AMDP-5) were analyzed using categorical methods.

Results: Mean daily anticholinergic dose was significantly higher overall for the risperidone group (0.68 ± 1.27 mg) than for the olanzapine group (0.27 ± 0.76 mg) (p = .002). When only patients who did not receive anticholinergic adjunct therapy were considered, no significant differences in the frequency of specific anticholinergic adverse events occurred in olanzapine-treated patients as compared with risperidone-treated patients (p >= .245). There was also no significant difference between olanzapine and risperidone in the frequency of any anticholinergic adverse event (p = .458).

Conclusion: At clinically effective doses, olanzapine and risperidone did not differ significantly in frequency of peripheral anticholinergic events. These results support the view that, for olanzapine and risperidone, in vitro anticholinergic receptor binding (K_i values) may not predict in vivo peripheral events.