L-methylfolate Plus SSRI or SNRI from Treatment Initiation Compared to SSRI or SNRI Monotherapy in a Major Depressive Episode

Abstract

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.

Figures

Figure 1

In patients with MDD, L-methylfolate plus SSRI/SNRI therapy was more effective than SSRI/SNRI monotherapy in improving CGI-S scores. In the L-methylfolate plus SSRI/SNRI group, 18.5% (n=17) demonstrated a major improvement in depressive symptoms (>2-point reduction in CGI-S) compared with 7.04% of the SSRI/SNRI monotherapy group (n=10) at 60 days (p=0.01).

Figure 2

In patients with MDD and with greater functional impairment (CGI-S=5), L-methylfolate plus SSRI/SNRI was more effective than SSRI/SNRI monotherapy in improving CGI-S scores. Forty percent of the L-methylfolate plus SSRI/SNRI group (n=35) demonstrated a major improvement in depressive symptoms (>2-point reduction in CGI-S) compared with 16.3% of the SSRI/SNRI monotherapy group (n=43) at 60 days (p=0.02).

Figure 3

Median time to >2-point improvement in the L-methylfolate plus SSRI/SNRI group occurred 54 days sooner at 177 days compared to 231 days in the SSRI/SNRI monotherapy group (p=0.03). This was a sustained effect throughout the observation period (max # of days: L-methylfolate plus SSRI/SNRI group=731 days; monotherapy group=780 days).

Figure 4

Median time to major improvement (>2-point) in patients with greater functional impairment was 85 days for the L-methylfolate plus SSRI/SNRI group and 150 days for the SSRI/SNRI group (p=0.018). This effect was sustained throughout the observation period (max # of days: L-methylfolate plus SSRI/SNRI group=731 days; monotherapy group=780 days).

Figure 5

Rank ordered based on average adverse events between the two groups. The overall rates of adverse events were not significantly different between the two groups (p=0.21).

Figure 6

Overall rate of discontinuation of antidepressant therapy due to adverse events was 34% for the SSRI/SNRI monotherapy group compared to 17.9% of patients in the L-methylfolate plus SSRI/SNRI combination group (p=0.0078).

Figure 7

The number of hospitalizations in the SSRI/SNRI monothearpy group was nearly 3 times greater than the L-methylfolate plus SSRI/SNRI group, although not statistically significant (p=0.357).