Pharmacogenetic testing to guide antipsychotic treatment: a systematic review and meta-analysis

The implementation of pharmacogenomic testing in clinical practise may bring improvement to antipsychotic treatment by preventing adverse events and improving treatment efficacy and compliance, therefore relieving a major cost-burden on the healthcare system. We conducted a systematic review and meta-analysis to investigate whether pharmacogenetic testing in individuals undergoing antipsychotic treatment improves clinical and economic outcomes. Several electronic databases were searched to identify relevant articles: MEDLINE (via Ovid), EMBASE (via Ovid), PsycINFO (via Ovid) and Cochrane Centrale Register of Controlled Trials. Data on the effect of pharmacogenetics testing on clinical and economic outcomes were synthesised and reported using descriptive statistics, summary tables and a narrative approach as a result of the substantial heterogeneity between the included studies. Where a meta-analysis was deemed possible, we calculated a standardised mean difference and 95% confidence interval between the pharmacogenetic-guided and treatment as usual group. In total, 14 eligible studies were included in the systematic review. Pharmacogenetics testing was generally associated with a reduction in inpatient, outpatient, and overall costs, compared to treatment as usual. A wide range of clinical outcomes were reported: adverse drug reactions, symptom severity, medication information (such as mean daily dose, number of antipsychotics prescribed), hospitalisations, polypharmacy, and physicians’ opinions of the pharmacogenetic-guided treatment. The meta-analysis did not find a statistically significant improvement in ADRs in the pharmacogenetics group compared to the treatment as usual group (UKU score SMD, 0.08; 95% CI, -0.11—0.26; p=0.42). However, there was evidence of clinical utility for studies which included antipsychotic medication when pharmacogenetic testing was conducted as part of a broader combinatorial treatment using a multigene panel. Pharmacogenetic testing to guide prescribing and dosing for antipsychotics has demonstrated significant cost-saving benefits and clinical improvements. However, this study has highlighted important gaps in the literature. To support the clinical implementation of pharmacogenetics testing into routine mental health care, studies with sufficient sample sizes that provide recommendations for patients who take antipsychotics based on a broad, multigene panel are required.