5-methyltetrahydrofolate and Bipolar-Disorder

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.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Registries; Tetrahydrofolates; Treatment Outcome

The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene plays a central role in folate metabolism. Many studies have demonstrated an association between MTHFR C677 T variant with depression, schizophrenia and bipolar disorder as one of them being comorbid to other. This has justified the use of folate supplement in psychiatric disorders mainly depression but still not in various other comorbid complex psychiatric disorders. Here we have tried to show how the l-methylfolate in conjunction with the conventional psychotropic drugs can be useful in a state of such complex psychiatric phenomenon and comorbid diagnosis with genetic polymorphism of MTHFR C677 T mutation.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Depressive Disorder, Treatment-Resistant; Drug Therapy, Combination; Fluoxetine; Humans; Lithium Compounds; Male; Methylenetetrahydrofolate Reductase (NADPH2); Obsessive-Compulsive Disorder; Polymorphism, Genetic; Tetrahydrofolates; Vitamin B Complex