Candidate gene analysis of pharmacodynamic targets for antipsychotic dosage.

AIM: In order to administer antipsychotic medication with the most beneficial outcome, the appropriate drug and dose needs to be identified. Though often not considered in pharmacogenetic studies, dosage plays an important role in treatment outcome. This study set out to analyze the association between 109 SNPs and antipsychotic dosage among schizophrenia patients. In a previous study, we tested 134 SNPs in regards to antipsychotic dosage. In the current study, we tested additional markers in the same candidate genes that we investigated in the previous study to confirm our previous findings.

METHODS: We included 263 participants with schizophrenia spectrum disorders between the ages of 18-75. Each participant was assessed cross-sectionally to collect clinical and antipsychotic treatment information through a semi-structured interview. The antipsychotic dosage for each individual was standardized according to chlorpromazine equivalents (CPZe), defined daily dose, and the percentage of maximum dosage (PM%). For each participant, 109 SNPs from 29 candidate genes were imputed or genotyped using a Customized Illumina Chip.

RESULTS: Polymorphisms in the GABRB1 gene were significantly associated with higher antipsychotic dosage according to CPZe and PM% standardization.

CONCLUSION: Our analysis suggests that variation in the GABRB1 gene may be significantly associated with antipsychotic dosage according to CPZe and PM% standardization. Antipsychotic dosage remains an integral measure for treatment response that warrants future pharmacogenetic testing and studies with larger sample sizes.