Comparative effectiveness of olanzapine and risperidone on clinical outcomes of schizophrenia in a low-income country.

BACKGROUND: Second-generation antipsychotics are the cornerstone of pharmacological treatment for schizophrenia. Although risperidone and olanzapine are among the most commonly prescribed agents, evidence comparing their real-world effectiveness in low-income countries remains limited. This evidence gap is largely attributable to differences in healthcare infrastructure, medication availability, continuity of care, and access to routine clinical monitoring, all of which may influence treatment outcomes. To address this gap, the present study compared the real-world effectiveness of olanzapine and risperidone on long-term clinical outcomes among patients with schizophrenia receiving routine psychiatric care in Ethiopia, a representative low-income country setting. METHODS: An institution-based retrospective cohort study was conducted at the University of Gondar Hospital among patients with schizophrenia. Data were collected from June 15 to November 15, 2024, among patients aged 18-65 years who had a DSM-5-TR diagnosis of schizophrenia, received maintenance treatment with either risperidone or olanzapine, and had at least one year of documented clinical follow-up. Symptom severity and clinical improvement were assessed using the Clinical Global Impression-Schizophrenia (CGI-SCH) and Clinical Global Impression-Improvement (CGI-I) scales, respectively. Extrapyramidal symptoms were evaluated using the Glasgow Antipsychotic Side-effect Scale (GASS), while medication adherence was measured using the Medication Adherence Rating Scale. Kaplan-Meier survival analysis, log-rank tests, one-way ANOVA, and multivariable Cox proportional hazards regression models were used for analysis. RESULT: A total of 1628 patients were included in the analysis, of whom 820 received risperidone and 808 received olanzapine. Overall symptom improvement was observed in 614 patients (37.7%), with no statistically significant difference between the two treatment groups in time to symptom reduction or overall improvement scores (p > 0.05). Extrapyramidal symptoms occurred more frequently among patients treated with risperidone than those treated with olanzapine (6.0%vs. 3.0%). In the multivariable Cox proportional hazards model, risperidone use was associated with a significantly higher hazard of developing extrapyramidal symptoms compared with olanzapine (AHR = 5.21, 95% CI: 2.39-11.34). Medication non-adherence was comparable between the two treatment groups. During follow-up, relapse occurred in 615 patients (37.8%), and risperidone treatment was associated with a higher risk of relapse compared with olanzapine (AHR=1.24; 95% CI: 1.08-1.43) after adjusting for potential confounders. CONCLUSION: In this retrospective Ethiopian cohort, risperidone and olanzapine showed comparable effectiveness in symptom improvement and medication adherence among patients with schizophrenia in routine clinical practice. However, olanzapine was associated with a lower risk of extrapyramidal symptoms and longer relapse-free survival compared with risperidone. These findings provide real-world evidence from a resource-limited psychiatric care setting and highlight the importance of individualized antipsychotic selection considering effectiveness, tolerability, and local treatment constraints.