Geographic variation in efficacy of atypical antipsychotics for the acute treatment of schizophrenia – An individual patient data meta-analysis

Taina Mattila, Tamar Wohlfarth, Maarten Koeter, Jitschak Storosum, Wim van den Brink, Lieuwe de Haan, Hubertus Leufkens, Damiaan Denys

Generalizability of efficacy results from medication trials across geographic regions is disputed. Geographic differences in factors such as patient characteristics, treatment practices and disease definitions might lead to differences in effect sizes across regions. This study examined geographic variation in efficacy results of schizophrenia trials with atypical antipsychotics using individual-patient data meta-analysis. Twenty-two studies including in total 5233 patients from three regions (North America, Europe, and the rest of the world) were included in the random effects meta-analysis. The effect size in North American patients was smaller in terms of mean change from baseline and in terms of responders (Hedge׳s G=0.37, 95% CI 0.28-0.46; OR 1.71, 95% CI 1.35-2.17) as compared to patients in Europe (Hedge׳s G=0.56, 95% CI 0.34-0.79; OR 2.25, 95% CI 1.62-3.12) and the rest of the world (Hedge׳s G=0.53, 95% CI 0.12-0.75; OR 2.61, 95% CI 1.66-4.17). The differences were not statistically significant. The observed differences remained when the confounding effect of unequal distribution of compounds was controlled for by analyzing separately the compounds that were studied across all three regions. Based on these results it cannot be excluded that there are differences in efficacy results of atypical antipsychotics trials across geographic regions. The observed trend towards differential efficacy across geographic regions warrants further examination of the determinants of these differences.