The influence of pharmacogenetics on the treatment-related outcomes of antidepressants and antipsychotics in Brazil: a systematic review.

Abstract

Introduction: Pharmacogenetics investigates how genetic variability influences drug response, with particular relevance in psychiatry, where treatment often requires trial-and-error approaches. However, most pharmacogenetic evidence derives from predominantly European populations, limiting its applicability to admixed populations like Brazil's. This study aimed to synthesize evidence on genetic determinants of antidepressant and antipsychotic treatment outcomes in Brazilian populations.

Methods: PubMed, Embase, BVS/Bireme and Google Scholar were systematically searched up to January 2026. Two reviewers screened studies and assessed quality. Eligible studies were observational, conducted in Brazil, evaluating pharmacogenetic influences on adults using antidepressants or antipsychotics.

Results: 19 papers were included, comprising 2,590 participants; 46% females. In schizophrenia, variants in CYP2C19, DRD1, DRD2, and CYP1A2 were associated with clozapine safety and response. In bipolar disorder, GAD1 variants were linked to lower Glu/GABA ratio. In major depressive disorder, all CYP2C19 ultrarapid metabolizers required combination therapy to achieve remission. For smoking cessation, CYP2B6 rs2279343 AA showed greater success with bupropion. In obsessive-compulsive disorder, HTR2A and HTR1B variants were associated with differential treatment response.

Conclusion: Brazilian studies report relevant gene-drug associations, but sample limitations reduce generalizability. Therefore, routine pharmacogenetic testing in Brazilian psychiatric practice remains premature.

Registration number: PROSPERO CRD42024533782.