Review Article: Homocysteine and folate metabolism in depression
Bottiglieri T. Homocysteine and folate metabolism in depression; Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2005;29:1103-12.
Abstract
Homocysteine is a sensitive marker of folate and vitamin B12 deficiency. Numerous studies have confirmed the association between folate deficiency and depression. It is not completely understood whether homocysteine is solely a marker for folate deficiency or if it may play a more direct role in the expression of mood disorders. This review describes the biochemical, neurochemical and clinical correlations of folate deficiency and hyperhomocysteinemia in relation to depression.
An open trial of methyltetrahydrofolate in elderly depressed patients.
Guaraldi GP, Fava M, Mazzi F, la Greca P; Ann Clin Psychiatry. 1993 Jun;5(2):101-5.
N = 20; Compound: 6(R,S)-5MTHF @ 50mg/day
5-methyltetrahydrofolate (MTHF) is a naturally occurring substance involved in the synthesis of s-adenosyl-l-methionine (SAMe), a major source of methyl groups in the brain. To assess the eficacy of a gastro-resistant, oral preparation of MTHF, 20 elderly patients with a DSM-III-R diagnosis of depressive disorder and a HAM-D-21 score > 18 underwent 6-weeks of open-label treatment with 50 mg per day of oral MTHF. Of these 20 patients, 16 completed at least 4 weeks of treatment and showed a markedly significant improvement in their depressive symptoms at endpoint, with 81% of them being considered responders. There were no clinically relevant changes in the routine laboratory tests during the study, and no adverse events considered to be definitely drug-related were reported.
Oral 5-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multi-center study.
Passeri M, Cucinotta D, Abate G, Senin U, Ventura A, Stramba Badiale M; .Aging, 1993 Feb;5(1):63-71.
N = 96; Compound: 6(R,S)-5MTHF @ 50mg/day
Is methylfolate effective in relieving major depression in chronic alcoholics? A hypothesis of treatment
C. Di Palma, R. Urani, R. Agricola, V. Giorgetti and G. Dalla Verde; Current Therapeutic Research; Volume 55, Issue 5 , May 1994, Pages 559-568
N = 36; Compound: 6(R,S)-5MTHF @ 90mg/day
Folate deficiency is often associated with depression. Chronic alcoholics, who usually present with reduced blood folate levels, are frequently affected by depression. After a 1-week run-in placebo period, 36 chronic alcoholics with major depression were treated with methylfolate (90 mg/d orally for 4 weeks) as an antidepressant. The surprisingly beneficial effects induced by methylfolate on depressive signs and symptoms of ethanol abusers should encourage more extensive experimental and clinical investigations to confirm these preliminary results. No adverse side effects were reported.
Enhancement of the antidepressant action of fluoxetine by folic acid: a randomized, placebo controlled trial
Coppen A., Bailey J.; Journal of Affective Disorders, Volume 60, November 2000, Pages 121-130
N = 127; Compound: Folic acid @ 0.5mg/day
Background: A consistent finding in major depression has been a low plasma and red cell folate which has also been linked to poor response to antidepressants. The present investigation was designed to investigate whether the co-administration of folic acid would enhance the antidepressant action of luoxetine.
Methods: 127 patients were randomly assigned to receive either 500 mg of folic acid or an identical looking placebo in addition to 20 mg fluoxetine daily. All patients met the DSM-III-R criteria for major depression and had a baseline Hamilton Rating Scale (17 item version) score for depression of 20 or more. Baseline and 10-week estimations of plasma folate and homocysteine were carried out.
Results: Patients receiving folate showed a significant increase in plasma folate. This was less in men than in women. Plasma homocysteine was significantly decreased in women by 20.6%, but there was no signiicant change in men. Overall there was a significantly greater improvement in the luoxetine plus folic acid group. This was confined to women where the mean Hamilton Rating Scale score on completion was 6.8 (S.D. 4.1) in the luoxetine plus folate group, as compared to 11.7 (S.D. 6.7) in the fluoxetine plus placebo group (P<0.001). A percentage of 93.9 of women, who received the folic acid supplement, showed a good response (>50% reduction in score) as compared to 61.1% of women who received placebo supplement (P<0.005). Eight (12.9%) patients in the fluoxetine plus folic acid group reported symptoms possibly or probably related to medication, whereas in the luoxetine plus placebo group 19 (29.7%) patients reported such symptoms (P<0.05).
Limitations and conclusions: Folic acid is a simple method of greatly improving the antidepressant action of fluoxetine and probably other antidepressants. Folic acid should be given in doses sufficient to decrease plasma homocysteine. Men require a higher dose of folic acid to achieve this than women, but more work is required to ascertain the optimum dose of folic acid.
Deplin® (7.5mg or 15mg L-methylfolate) is a prescription medical food for the dietary management of suboptimal folate levels in depressed patients.
Legal Disclaimer / Privacy Notice
Deplin.com © 2010