Effectiveness of a Pharmacogenetic Tool at Improving Treatment Efficacy in Major Depressive Disorder: A Meta-Analysis of Three Clinical Studies

Silvia Vilches, Miquel Tuson, Eduard Vieta, Enric Álvarez, Jordi Espadaler, Silvia Vilches, Miquel Tuson, Eduard Vieta, Enric Álvarez, Jordi Espadaler

Abstract

Several pharmacogenetic tests to support drug selection in psychiatric patients have recently become available. The current meta-analysis aimed to assess the clinical utility of a commercial pharmacogenetic-based tool for psychiatry (Neuropharmagen®) in the treatment management of depressive patients. Random-effects meta-analysis of clinical studies that had examined the effect of this tool on the improvement of depressive patients was performed. Effects were summarized as standardized differences between treatment groups. A total of 450 eligible subjects from three clinical studies were examined. The random effects model estimated a statistically significant effect size for the pharmacogenetic-guided prescription (d = 0.34, 95% CI = 0.11-0.56, p-value = 0.004), which corresponded to approximately a 1.8-fold increase in the odds of clinical response for pharmacogenetic-guided vs. unguided drug selection. After exclusion of patients with mild depression, the pooled estimated effect size increased to 0.42 (95% CI = 0.19-0.65, p-value = 0.004, n = 287), corresponding to an OR = 2.14 (95% CI = 1.40-3.27). These results support the clinical utility of this pharmacogenetic-based tool in the improvement of health outcomes in patients with depression, especially those with moderate-severe depression. Additional pragmatic RCTs are warranted to consolidate these findings in other patient populations.

Keywords: antidepressants; depression; genetic; pharmacogenetics; psychiatry; randomized controlled trials.

Conflict of interest statement

S.V. and M.T. are employees of AB-Biotics. J.E. is employee and minor stock shareholder in AB-Biotics. M.T. and J.E. participated in the study design, analysis, interpretation of data and writing the manuscripts of the main results of the GENEPSI and the AB-GEN studies. AB-Biotics partially funded the GENEPSI and the AB-GEN studies, and genotyped and provided the PGx report results in all three trials included. E.V. has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Galenica, Janssen, Lundbeck, Novartis, Otsuka, Sage, Sanofi-Aventis, and Takeda. E.A. has received consulting and educational honoraria from Eli Lilly, Lundbeck, Otsuka, Pfizer, and Sanofi-Aventis. E.A. has participated as principal local investigator in clinical trials sponsored by AB-Biotics, Bristol-Myers Squibb, Eli Lilly, and Sanofi-Aventis, and has served as national coordinator of clinical trials sponsored by Servier and Lundbeck.

Figures

Figure 1
Figure 1
Individual and pooled effect sizes for clinical response based on CGI-S score change.
Figure 2
Figure 2
Individual and pooled effect sizes for clinical response based on HDRS-17 score change.

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