title: Long-term efficacy, safety, and tolerability of L-methylfolate calcium 15 mg as adjunctive therapy with selective serotonin reuptake inhibitors: a 12-month, open-label study following a placebo-controlled acute study.
abstract: OBJECTIVE
  To evaluate remission and recovery, safety, and tolerability for up to 12 months of open-label adjunctive L-methylfolate calcium 15 mg.
  
  
  METHODS
  Subjects in this analysis were adult outpatients (18-65 years) enrolled from 2 acute, double-blind, placebo-controlled trials comparing adjunctive L-methylfolate and placebo for DSM-IV major depressive disorder (MDD) with an inadequate response to monotherapy selective serotonin reuptake inhibitor (SSRI). Subjects who completed the acute trial were offered to enroll in a 12-month, open-label treatment phase with L-methylfolate and continued SSRI treatment, with scheduled visits for efficacy, safety, and tolerability every 12 weeks. Subjects were enrolled between September 2006 and February 2010. Efficacy outcomes included predefined criteria for response, remission, recovery, relapse, and recurrence. Subjects treated with adjunctive L-methylfolate 15 mg were included in the efficacy analysis.
  
  
  RESULTS
  Of 68 subjects who met criteria for the 12-month open-label phase, 38% (n = 26) achieved full recovery, and none experienced a recurrence of MDD. For subjects entering the open-label phase in remission (n = 11), 91% (n = 10) achieved full recovery with L-methylfolate 15 mg, and none experienced a relapse or recurrence. Among 57 subjects who entered the open-label phase as nonremitted, 61% (n = 35) achieved remission. Of subjects who entered the open-label phase with a response without remission (n = 4), 50% (n = 2) had full recovery, and of subjects entering the open-label phase with no response (n = 53), 26% (n = 14) met recovery criteria.
  
  
  CONCLUSIONS
  Adjunctive L-methylfolate 15 mg/d may be an early option in patients who fail to adequately respond to antidepressant monotherapy, with preliminary evidence demonstrating sustained remission and sustained recovery.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00321152.
authors.affiliation: 1700 Van Buren St, 5th Fl, Chicago, IL 60612 john_zajecka@rush.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Zajecka
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: Richard C
authors.initials: RC
authors.lastname: Shelton
authors.forename: Lori W
authors.initials: LW
authors.lastname: Barrentine
authors.forename: Page
authors.initials: P
authors.lastname: Young
authors.forename: George I
authors.initials: GI
authors.lastname: Papakostas
mesh_terms: D000328:Adult; D000368:Aged; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013763:Tetrahydrofolates / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors; D013763:Tetrahydrofolates; C005984:5-methyltetrahydrofolate