Pharmacogenomic diversity in psychiatry: Challenges and Opportunities in Africa

Pharmacogenomic studies on psychiatric drugs have slowly identified genetic variations that influence drug metabolism and treatment effectiveness in patients with mental illness. However, most of these studies have predominantly centered on people of European descent, leaving a substantial knowledge gap on the clinical implications of current pharmacogenomic evidence in multi-ancestry populations such as Africans. Thus, whether pharmacogenomic (PGx) genetic testing implemented in European populations would be valid for a population of African origin is unknown. The objective of this review was to appraise previous psychiatric pharmacogenomic studies in Africa and highlight challenges and opportunities to initiate PGx testing in the region. A systematic literature search was conducted on PubMed, Scopus, and Web of Science to identify studies published in the English language up to January 26, 2024. The primary outcomes were treatment response, remission, side effects, and drug metabolism in African psychiatric patients. The review included 42 pharmacogenomic studies that explored the genetic profiles of psychiatric patients in Africa. Despite the limited number of studies, our review found strong evidence of pharmacogenomic diversity within the African populations, emphasizing the importance of pharmacogenomic research in this population. A high degree of variability and differences in the frequencies of cytochrome P450 (CYPs) genotypes have been reported within the African population. It is estimated that 28% of North Africans and Ethiopians are ultrarapid metabolizers of several medications, mainly attributed to the increased activity of the CYP2D6 enzyme. This prevalence is significantly higher than that among Caucasians (10%), or Hispanics, Chinese, or Japanese populations (1%). Due to the defective CYP2C19*2 allele (at a frequency of 14%) and CYP2C19*3 allele (2% frequency), 5.2% of Ethiopians were identified as poor metabolizers of S-mephenytoin, a probe substrate used to assess the activity of the cytochrome P450 enzyme. In Tunisian patients with schizophrenia, genotyping the CYP1A2 gene and using therapeutic drug monitoring (TDM) improved the effectiveness and safety of clozapine. Among South African patients with schizophrenia, antipsychotic treatment response was associated with two gene variants (rs13025959 in the MYO7B gene with the C allele and rs10380 in the MTRR gene with the T allele). Overall, the review has identified evidence of pharmacogenomic diversity in African populations and recommended expanding pharmacogenomic studies while introducing PGx testing in this population. For the few characterized genes, Africans showed qualitative and quantitative differences in the profile of pharmacogenetic variants when compared to other ethnic groups. Limited research funding, inadequate infrastructure, and a shortage of skilled human resources might be a challenge, but by building upon local successes and through collaborations with international partners, it is possible to establish pharmacogenomic biobanks and leverage global genetic resources to initiate personalized treatment approaches in Africa.