methylfolate as adjunctive therapy for SSRI- resistant major depression: results of two randomized, double-blind, paralled-sequential trials.
The authors conducted two multicenter sequential parallel comparison design trials to investigate the effect of L-
In the first trial, 148 outpatients with SSRI-resistant major depressive disorder were enrolled in a 60-day study divided into two 30-day periods. Patients were randomly assigned, 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. SSRI dosages were kept constant throughout the study. In the second trial, with 75 patients, the design was identical to the first, except that the l-methylfolate dosage was 15 mg/day during both 30-day periods.
In the first trial, no significant difference was observed in outcomes between the treatment groups. In the second trial, adjunctive L-
ClinicalTrials.gov NCT00321152 NCT00955955.
Papakostas GI, Shelton RC, Zajecka JM, Etemad B, Rickels K, Clain A, Baer L, Dalton ED, Sacco GR, Schoenfeld D, Pencina M, Meisner A, Bottiglieri T, Nelson E, Mischoulon D, Alpert JE, Barbee JG, Zisook S, Fava M:
Am J Psychiatry 169(12):1267-1274, 2012 23212058