459 Clinical Utility of Pharmacogenetic Tests When Prescribing Antidepressant Therapy for Depression, A Systematic Review and Meta-analysis of Randomised Controlled Trials
Authors: Jethwa S , Almomani H , Donyai P 
Published: April 2023

Abstract

Introduction
Pharmacogenetic testing when prescribing medicines has the potential to reduce harmful side effects, optimise treatment, and improve clinical outcomes. Depression is a major global disease burden with high economic costs and it’s becoming more prevalent (1). There is a growing number of clinical trials and reviews that support the use of pharmacogenetic testing for depression and more results are available from randomised controlled trials (RCTs) that were completed recently to warrant a new systematic review (2).

Aim
The aim was to evaluate the clinical utility of pharmacogenetic tests when prescribing antidepressant therapy for depression (including mild, moderate, and major depression) by comparing the remission rate, antidepressant response and adverse events from RCTs for the pharmacogenetic guided therapy group and the treatment as usual group (TAU) through a systematic review and meta-analysis.

Methods
The PICO inclusion criteria are adults with depression requiring antidepressant therapy for depression. The intervention is a pharmacogenetic gene test(s) and the comparator is usual treatment. The outcomes are depression remission, antidepressant response and adverse events. This research was undertaken between April and September 2022 by the main author (SJ). The second author (HA) peer reviewed the title/abstract screening, full text review, and the third author (PD) provided supervisory support. A systematic literature search was completed using Embase, Medline, Cochrane, and PubMed databases according to a published PROSPERO protocol. Articles published between 2000 - 2022 were eligible. Only RCTs that had TAU as the comparator were included. Bias and quality assessments were carried out using the RoB 2 tool. Studies with a high risk of bias were excluded. Heterogeneity was calculated using I2. A random effects model meta-analysis was conducted using RevMan.

Results
In total, 520 articles were retrieved at first search (excluding duplicates) and seven double-blinded (rater and patient blinded) RCTs were identified that met the full inclusion and exclusion criteria. The RCTs were based in North America (5), Australia (1) and Europe (1). The meta-analysis revealed the remission rate was greater for pharmacogenetic guided groups compared to the TAU groups, pooled risk ratio (RR) = 1.54 (95% CI 1.07-2.21, p = 0.02). For the response rate, results from 6 double blinded RCTs which measured this had a pooled RR= 1.23 (95% CI 0.95-1.59, p = 0.11) which indicates a greater (but not statistically significant) response rate in the pharmacogenetic guided group.

Conclusion
A limitation of this study is that it showed improvement in remission but not response rate, which is potentially due to response data missing from one of the seven pooled studies. Pharmacogenetic tests might have the potential to improve remission and response rates for antidepressant therapy compared to treatment as usual. However, further studies in the UK are warranted to help determine whether pharmacogenetic tests should be used in an NHS setting.

References
1. Proudman D, Greenberg P, Nellesen D. The growing burden of Major Depressive Disorders (MDD): Implications for Researchers and Policy Makers. PharmacoEconomics. 2021; 39(6): 619-25.
2. Bousman et al, Pharmacogenetic Tests and Depressive Symptom Remission: A Meta-analysis of Randomized Controlled Trials. Pharmacogenomics. 2019; 20(1):37-47.