Adjunct L-methylfolate may improve major depressive symptoms

Augmentation therapy with L-methylfolate may benefit patients who have been diagnosed with major depressive disorder and have had a partial or no response to SSRIs.

The study, published in the December issue of The American Journal of Psychiatry, reports on data from two trials and demonstrates that adjunctive L-methylfolate 15 mg daily may be a safe and effective treatment for patients who have had a partial response or no response to selective serotonin reuptake inhibitors (SSRIs).

In the first trial, the authors enrolled 148 outpatients with SSRI-resistant major depressive disorder and randomly assigned them in a 2:3:3 ratio to receive L-methylfolate for 60 days (7.5 mg/day for 30 days followed by 15 mg/day for 30 days), placebo for 30 days followed by L-methylfolate (7.5 mg/day) for 30 days, or placebo for 60 days. The second trial was designed identically; however, the L-methylfolate dose was 15 mg/day during both 30-day periods. The authors enrolled 75 patients into the second trial.

Investigators observed no significant difference in outcomes between the treatment groups in trial 1, but in trial 2, adjunctive L-methylfolate at 15 mg/day demonstrated significantly greater efficacy. Twice as many patients achieved response in 30 days and experienced 84% greater reduction in depressive symptoms compared with continued SSRI therapy plus placebo, according to Pamlab, maker of Deplin, a medical food containing L-methylfolate.

The authors found L-methylfolate to be well tolerated, and concluded that "15 mg/day may constitute an effective, safe, and relatively well tolerated treatment strategy for patients with major depressive disorder who have a partial response or no response to SSRIs."

The study was supported by a grant from Pamlab.