title: L-Methylfolate For Bipolar I depressive episodes: An open trial proof-of-concept registry.
abstract: L-methylfolate is a compelling candidate to treat bipolar I major depressive episodes. While approved as an adjunct for unipolar major depressive disorder, no studies have been done to assess the tolerability, safety, and efficacy of L-methylfolate for bipolar depression. As a first step, we developed a registry of bipolar patients treated with L-methylfolate to examine tolerability and outcomes.
  
  
  
  Subjects (N=10) received treatment as usual plus daily L-methylfolate 15mg for 6 weeks in this open-label registry. Depressive symptoms were assessed with the Montgomery Asberg Depression Rating Scale (MADRS) and manic symptoms with the Young Mania Rating Scale (YMRS). Effect size was measured with Cohen's d to provide an estimate of potential efficacy.
  
  
  
  The pre-treatment mean (SD) MADRS score was 23.4 (4.34); the post-treatment score was 13.9 (8.24). Cohen's d was 1.19. At post-treatment, 6/10 patients had at least 50% MADRS improvement, and 4/10 patients exhibited remission with MADRS≤10. The pre-treatment YMRS score was 3.2 (3.0); the post-treatment score was 2.7 (5.2). Cohen's d was 0.17.
  
  
  
  This registry was a small open-label clinical trial for a fluctuating disorder. We cannot rule out that our results are due to regression to the mean. A controlled trial is warranted.
  
  
  
  This first proof-of-concept open registry suggests that L-methylfolate in combination with treatment as usual has potential to treat bipolar depression.
authors: Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. Electronic address: anierenberg@partners.org.
authors: Andrew A
authors: AA
authors: Nierenberg
authors: Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors: Rebecca
authors: R
authors: Montana
authors: Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors: Gustavo
authors: G
authors: Kinrys
authors: Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors: Thilo
authors: T
authors: Deckersbach
authors: Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors: Steven
authors: S
authors: Dufour
authors: Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Samsung Medical Center, Seoul, Korea.
authors: Ji Hyun
authors: JH
authors: Baek
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012042:Registries; D013763:Tetrahydrofolates / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D013763:Tetrahydrofolates; C005984:5-methyltetrahydrofolate
keywords: Bipolar disorder; Deplin; Depression; L-methylfolate