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Meta-Analysis
. 2022 Dec;112(6):1303-1317.
doi: 10.1002/cpt.2748. Epub 2022 Oct 11.

Pharmacogenomic Testing and Depressive Symptom Remission: A Systematic Review and Meta-Analysis of Prospective, Controlled Clinical Trials

Lisa C Brown  1 , Joseph D Stanton  2 , Kanika Bharthi  3 , Abdullah Al Maruf  4   5   6 , Daniel J Müller  7   8   9 , Chad A Bousman  4   10   11
Affiliations
Meta-Analysis

Pharmacogenomic Testing and Depressive Symptom Remission: A Systematic Review and Meta-Analysis of Prospective, Controlled Clinical Trials

Lisa C Brown et al. Clin Pharmacol Ther. 2022 Dec.

Abstract

Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical efficacy of this strategy has been questioned. We systematically reviewed and meta-analyzed clinical trials for an association between the use of PGx-guided antidepressant therapy and depressive symptom remission in patients with major depressive disorder (MDD). We included prospective, controlled clinical trials published in English up to July 12, 2022. Data extraction and synthesis adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Each trial was assessed for risk of bias and a random-effects model was used to estimate pooled risk ratios. Thirteen trials comprising 4,767 patients were analyzed, including 10 randomized controlled trials, and three open label trials. Across all included trials, those that received PGx-guided antidepressant therapy (n = 2,395) were 1.41 (95% confidence interval (CI) = 1.15-1.74, P = 0.001) more likely to achieve remission compared with those that received unguided antidepressant therapy (n = 2,372). Pooled risk ratios for randomized controlled trials and open label trials were 1.46 (95% CI: 1.13-1.88) and 1.26 (95% CI = 0.84-1.88), respectively. These results suggest that PGx-guided antidepressant therapy is associated with a modest but significant increase in depressive symptom remission in adults with MDD. Efforts to address the heterogeneity in PGx test composition (i.e., genes and alleles tested) and accompanying prescribing recommendations across trials will likely reduce the uncertainty about the efficacy of PGx-guided antidepressant therapy in the literature.

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Conflict of interest statement

L.C.B. is Founder and Principal Consultant for Great Scott! Consulting LLC, a PGx consulting company, and stockholder of Myriad Genetics. J.D.S. is an employee of Tempus Labs. D.J.M. reports to have been a co‐investigator on two pharmacogenomic studies where genetic test kits were provided as in‐kind contribution by Myriad Neuroscience. He has not received any payments or any equity, stocks, or options from any pharmacogenomic companies. C.B. is Founder and CEO of Sequence2Script Inc. All other authors declared no competing interests for this work.

Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) diagram. Of 150 records screened, and five previous studies analyzed, our search resulted in a total of 13 new studies for inclusion in the analysis.
Figure 2
Figure 2
Meta‐analysis of PGx RCTs, open label, and combined. Pooled risk ratios were calculated using random‐effects models. CI, confidence interval; PGx, Pharmacogenomic; RCTs, randomized controlled trials.
See this image and copyright information in PMC

References

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