Meta regression: Relationship between antipsychotic receptor binding profiles and side-effects

Our objective was to examine the association between antipsychotic receptor binding profiles and the magnitude of common side-effects. We used regression analysis to examine the association between the receptor binding affinities of antipsychotic agents (log Ki) and degree of specific antipsychotic side-effects. Data on magnitude of weight gain, prolactin increase and QTc prolongation (in Standardized Mean Difference) and risk of sedation and extrapyramidal symptoms (in Odds Ratio) between individual antipsychotic medications as compared to placebo was based on a recent network meta-analysis examining the treatment of schizophrenia. Receptor affinities (in log Ki) were examined for the D2, 5-HT1A, 5-HT2A, 5-HT2C, H1, alpha1, alpha2, M1, M3 and M4 receptors. Medications were weighted in the analysis using the generic inverse variance method utilizing variance estimates from the previous meta-analysis. Magnitude of weight gain was significantly associated with the affinity of antipsychotic medications to M1, M3, 5-HT2C and H1 receptors. Risk of sedation was significantly associated with the affinity to the M1 and M4 receptors. Magnitude of hyperprolactinemia was significantly associated with the affinity to M1 and M4 receptors. Risk of extrapyramidal side effects was associated with the affinity to 5-HT2C and M1 receptors. QT prolongation was not significantly associated with antipsychotic receptor affinities. Our meta-analysis demonstrated that increased affinity of antipsychotics for certain receptors are significantly associated with higher risk of sedation, hyperprolactinemia, extrapyramidal side effects and weight gain.