L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials
Papakostas GI, et al
Published in American Journal of Psychiatry
Methodology
Two multicentre randomised, double-blind, sequential parallel comparison design trials of 60 days split into two 30-day periods; adjunctive L-methylfolate at 7.5 mg/day escalating to 15 mg/day (trial 1) or 15 mg/day throughout (trial 2) with SSRI dose held constant.
Key Findings
Two sequential parallel comparison trials tested L-methylfolate added to a stable SSRI in patients with SSRI-resistant major depression. In the first trial of 148 outpatients, using 7.5 mg/day then 15 mg/day across two 30-day periods, no significant difference between treatment groups was found. In the second trial of 75 patients using 15 mg/day throughout, adjunctive L-methylfolate significantly outperformed placebo on both primary outcomes (response rate and change in depression score) and two secondary severity measures, with a number needed to treat of about six. Adverse event rates did not differ from placebo.
Conclusions
Adjunctive L-methylfolate at 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.
Limitations
The positive result comes from the smaller of the two trials (75 patients) at the higher dose while the larger 148-patient trial was negative; each treatment period lasted only 30 days and the sequential parallel comparison design is uncommon.
Supplements Studied
Adjunctive L-methylfolate at 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.
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