Assessment of Pharmacogenomic Variation in CYP2D6 and Its Influence on Antidepressant Response in a Nigerian Population

Background: CYP2D6 is a cytochrome P450 enzyme responsible for the metabolism of numerous antidepressants. Pharmacogenomic variation in CYP2D6 significantly influences drug plasma levels, efficacy, and adverse effect profiles. African populations exhibit unique CYP2D6 allele frequencies, yet pharmacogenomic data from Nigerian patients remain sparse. This study assessed CYP2D6 variant frequency and its relationship with antidepressant response in a Nigerian population. Methods: Ninety patients with major depressive disorder receiving either amitriptyline, fluoxetine, or venlafaxine were recruited from psychiatric outpatient clinics in three geopolitical zones (South West, South East, North Central). CYP2D6 genotyping was performed using PCR-RFLP for key alleles including CYP2D6-17 (common in African populations), CYP2D6-4, and CYP2D6-10. Metaboliser phenotypes were assigned and correlated with six-week Hamilton Depression Rating Scale (HAM-D) scores and adverse event frequency. Results: CYP2D6-17 was the most prevalent variant (39%). Poor metabolisers (8%) showed significantly higher adverse event rates for amitriptyline (p less than 0.05). Ultra-rapid metabolisers (11%) had significantly poorer antidepressant response at six weeks (p less than 0.01). Conclusion: CYP2D6 polymorphism significantly influences antidepressant outcomes in Nigerian patients. Incorporating pharmacogenomic screening into psychiatric prescribing could optimise therapeutic decisions in this population. Keywords: pharmacogenomics, CYP2D6, antidepressants, Nigerian population, drug metabolism