Influence of Cultural Differences and Genetic Polymorphisms on Schizophrenia Management: An Exploratory Targeted Literature Review

Abstract: Objective: Cultural differences impact schizophrenia management across countries and may complicate the evaluation of new therapeutics. Genetic polymorphisms are associated with predisposition to schizophrenia, disease course, and treatment outcomes, and vary among patient populations (eg, East Asian, South Asian, white). This study was designed to examine what factors should be considered when assessing the efficacy of new schizophrenia therapeutics, particularly olanzapine, in United States (US)- and Asia-based populations. Methods: A targeted literature review was conducted by searching PubMed for data published 2011–2021 regarding cultural and genetic differences in patients with schizophrenia between the US and Japan or China. Results are summarized qualitatively. Results: In any given population, cultural considerations impacting clinical trial design include choice of patient-reported outcome measures, extent of placebo response, and willingness to participate in a placebo-controlled study/study that requires study site confinement. Additionally, regional differences in clinical trial results may be expected because of variation in the prevalence of genetic polymorphisms influencing drug metabolism (eg, CYP1A2), response to treatment (eg, PANSS scores), and risk of particular adverse events (eg, weight gain, hyperinsulinemia). Conclusions: Based on this targeted literature review, several factors may influence cultural, hereditary, and regional differences in schizophrenia management. Such differences should be considered when designing multinational trials, whether in response to the drive to increase diversity in clinical trials or to satisfy regulatory agency guidance/requirements. Further and more systematic review of published literature is needed to investigate and integrate the implications of these differences for schizophrenia management and the development of new therapeutics.Short Description: Several factors may influence cultural, hereditary, and regional differences in schizophrenia management. A targeted literature review was conducted to examine these differences with respect to antipsychotic treatment in patients with schizophrenia in the US and Japan or China. In addition to cultural factors influencing participation in clinical trials, genetic polymorphisms affecting drug metabolism, treatment response, or likelihood of adverse events may impact efficacy and safety outcomes in clinical trials.Name of Sponsoring Organization(s): Teva Branded Pharmaceutical Products R&D, Inc.