Abstract:
BACKGROUND : Contradictory information exists regarding the influence of CYP2D6 polymorphisms on adverse drug
reactions (ADRs) (extrapyramidal symptoms (EPS) and weight gain) related to risperidone treatment. This
prompted us to evaluate the influence of CYP2D6 genetic variation in a cohort of South African patients who
presented with marked movement disorders and/or weight gain while on risperidone treatment.
METHODS : Patients who were experiencing marked risperidone ADRs were recruited from Weskoppies Public
Psychiatric Hospital. As poor or intermediate metabolism was expected, comprehensive CYP2D6 sequence
variations were evaluated using XL-PCR + Sequencing.
RESULTS : No statistically significant association was found between CYP2D6 poor metabolism and risperidone
ADRs. An inverse relationship between EPS and weight gain was however identified. A novel CYP2D6 allele
was identified which is unlikely to affect metabolism based on in silico evaluation.
CONCLUSION : CYP2D6 variation appeared not to be a good pharmacogenetic marker for predicting risperidonerelated
ADRs in this naturalistic South African cohort. Evaluation of a larger cohort would be needed to confirm
these observations, including an examination of the role of potential intermediaries between the hypothesised
genetic and clinical phenotypes.
