Objective: Evaluate the efficacy of L-methylfolate in combination with SSRI or SNRI compared to SSRI or SNRI monotherapy in a major depressive episode.
Design: A retrospective analysis of L-methylfolate plus SSRI/SNRI at treatment initiation (n=95) and SSRI/SNRI monotherapy (n=147) from patient charts.
Setting: Outpatient, private psychiatric clinic/practice.
Participants: Adults 18 to 70 with major depressive episode (single or recurrent).
Measurements: Clinical Global Impressions-Severity (CGI-S) and safety/tolerability measures.
Results: Major improvement (CGI-S reduced by ≥2 points) was experienced by 18.5 percent of L-methylfolate plus SSRI/SNRI patients (CGI-S=4-5) compared to 7.04 percent of SSRI/SNRI monotherapy (p=0.01) patients at 60 days. Forty percent of L-methylfolate plus SSRI/SNRI patients with greater functional impairment (CGI-S=5) experienced major improvement compared to 16.3 percent of SSRI/SNRI monotherapy patients (p=0.02). Median times to major improvement were 177 days for L-methylfolate plus SSRI/SNRI patients and 231 days for SSRI/SNRI monotherapy patients (p=0.03). Median time to major improvement for L-methylfolate plus SSRI/SNRI patients with greater functional impairment (CGI-S=5) was 85 days and 150 days for SSRI/SNRI monotherapy patients (p=0.018). There were no significant differences between groups in adverse events. Discontinuation due to adverse events was 17.9 percent in L-methylfolate plus SSRI/SNRI patients compared to 34 percent in the SSRI/SNRI monotherapy patients over duration of the study (p=0.0078).
Conclusion: L-methylfolate plus antidepressant at treatment onset was more effective in improving depressive symptoms and function measured by CGI-S scores within 60 days than antidepressant monotherapy, led to major symptomatic improvement more rapidly than SSRI/SNRI monotherapy, and was better tolerated.
Keywords: L-methylfolate; SNRI; SSRI; folate; major depressive disorder; treatment initiation.