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Hyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P‐glycoprotein. Genetic variants of P‐glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland.    Aims  To investigate possible associations between  MDR1/ABCB1  gene polymorphisms and antipsychotic drug‐induced hyperprolactinaemia in Russian patients with schizophrenia and to determine possible differences between risperidone/paliperidone and other antipsychotics.    Methods  In total, 446 patients with schizophrenia were included from 3 psychiatric hospitals in Siberia. Blood samples were obtained in a cross‐sectional study design for DNA extraction and prolactin measurement. Associations between hyperprolactinaemia and 8  MDR1/ABCB1  gene‐polymorphisms were assessed using logistic regression analysis accounting for covariates. The analysis was repeated in a patient subgroup using risperidone or paliperidone.    Results  We did not observe an association between any of the 8 single nucleotide polymorphisms and the prevalence of antipsychotic‐induced hyperprolactinaemia in the total patient population. However, in the risperidone/paliperidone subgroup, the single nucleotide polymorphism rs2032582 (G2677T) was found to be negatively associated with risperidone/paliperidone‐induced hyperprolactinaemia.    Conclusion  This study revealed a significant association between the  ABCB1  gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone‐induced hyperprolactinaemia.

Association between 8 P‐glycoprotein (MDR1/ABCB1) gene polymorphisms and antipsychotic drug‐induced hyperprolactinaemia