Folate metabolism biomarkers from two randomised placebo-controlled clinical studies with paroxetine and venlafaxine

Abstract

Objectives

Based on the hypothesis of a role for folate and vitamin B12 in major depressive disorders (MDD), we aimed at validating the association between folate pathway biomarkers and depression or antidepressant response in clinical trial populations.

Methods

We investigated serum levels erythrocyte folate and serum levels of homocysteine, vitamin B12, and folate as disease and response biomarkers for MDD in two independent randomised, placebo-controlled clinical trials, where paroxetine or venlafaxine were used as active controls, for a total of 881 patients.

Results

Significant but weak correlations between depression severity and biomarker levels could be detected in the paroxetine study for serum folate and vitamin B12, with no correlations for any biomarker in the venlafaxine study. Besides a weak association for erythrocyte folate in the venlafaxine study, no significant associations were observed between treatment response and pre-treatment levels of any of the biomarkers tested.

Conclusions

Notwithstanding the relatively large number of patients tested, we did not find consistent associations between folate biomarkers and MDD severity, or response to paroxetine and venlafaxine. Our results may be related to the particular study design or clinical population; however, our findings do not support the hypothesis of a dysfunction of one-carbon metabolism in MDD.

Keywords:

• Antidepressant
• folate
• depression
• biomarkers

Acknowledgements

The authors wish to acknowledge the GSK372475 clinical team, and in particular Dr. Pierandrea Muglia, Dr. Agnes Lavergne and Dr. Roberto Gomeni, for helpful discussions during the conduct of the study.

Disclosure statement

LC, EI, BD, ER, RA, ED and SML were employees of GlaxoSmithKline at the time of the study. ED was an employee of F. Hoffmann-La Roche until 2015 and later served as a consultant to Roche and Pierre-Fabre in the area of genetic biomarkers. ER was an employee of Takeda until March 2020. RA is currently an employee of Takeda; SML is an employee of Indivior; EI is an employee of Leadiant.