Comparative Risk of Extrapyramidal Symptoms Between Risperidone and Olanzapine
Olanzapine has a significantly lower risk of extrapyramidal symptoms (EPS) compared to risperidone, with approximately 35.8% of olanzapine patients experiencing EPS versus 55.1% of risperidone patients. 1
Direct Comparison of EPS Risk
In a head-to-head randomized controlled trial comparing risperidone and olanzapine in patients with schizophrenia or schizoaffective disorder, similar proportions reported extrapyramidal symptoms (24% for risperidone vs. 20% for olanzapine), though this specific study did not find statistically significant differences in EPS severity 2
The EIRE study, which examined EPS in schizophrenia outpatients, found that risperidone had significantly higher rates of EPS (55.1%) compared to olanzapine (35.8%), a difference that was statistically significant 1
Akathisia specifically was more frequent with risperidone (19.7%) than with olanzapine (11.4%) 1
Relative Ranking of Antipsychotics by EPS Risk
When ranking atypical antipsychotics by EPS risk, olanzapine consistently ranks lower than risperidone, particularly when risperidone is used at higher doses 3
The tentative ranking of atypical antipsychotics by EPS risk places olanzapine with lower risk than risperidone at higher doses, though risperidone's risk decreases at lower doses 3
Mechanism of EPS Risk Differences
Olanzapine's lower EPS risk may be partially attributed to its antimuscarinic activity, which risperidone lacks 3
Both medications have high antiserotonergic (5-HT2A receptor) potency, which may help limit EPS, but olanzapine's additional pharmacological properties appear to provide further protection 3
Special Populations and Considerations
In patients with dementia, risperidone doses above 2 mg/day significantly increase the risk of extrapyramidal symptoms 4
For patients who have experienced EPS in the past, risperidone may not offer reduced risk compared to typical antipsychotics (RR 1.30; 95% CI 0.24 to 7.18), suggesting olanzapine might be preferable in this population 5
In a study of cancer patients with delirium, approximately one in five patients experienced extrapyramidal side effects with both risperidone and olanzapine, suggesting similar risks in this specific population 6
Clinical Implications
When selecting between these medications, the lower EPS risk with olanzapine should be weighed against its greater propensity for weight gain (27% of olanzapine patients vs. 12% of risperidone patients gained ≥7% body weight in comparative trials) 2
Regular monitoring for EPS is essential when using any antipsychotic, including both risperidone and olanzapine 7
For patients particularly vulnerable to EPS (such as elderly patients or those with prior EPS), olanzapine may be the preferred choice between these two medications 5
Atypical antipsychotics like olanzapine and risperidone generally have diminished risk of EPS and tardive dyskinesia compared to typical antipsychotics, though this advantage is more pronounced with olanzapine 7, 1