Folate for depression

This systematic review was undertaken to see if giving folate to people with depressive disorders reduced their depressive symptoms. Three randomized trials were identified, involving a total of 247 people. In all three trials, folate was well tolerated. In two of these trials, folate was added to other antidepressant drug treatment and there was limited evidence that folate helped. In the third trial, folate was compared to trazodone, an antidepressant drug. No difference was found. There is therefore limited evidence that adding folate to other antidepressant may be helpful, but larger trials are needed before patients and clinicians can be confident that it will be helpful.

Authors' conclusions: 

The limited available evidence suggests folate may have a potential role as a supplement to other treatment for depression. It is currently unclear if this is the case both for people with normal folate levels, and for those with folate deficiency.

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Background: 

There are a number of effective interventions for the treatment of depression. It is possible that the efficacy of these treatments will be improved further by the use of adjunctive therapies such as folate.

Objectives: 

1. To determine the effectiveness of folate in the treatment of depression
2. To determine the adverse effects and acceptability of treatment with folate.

Search strategy: 

The Cochrane CENTRAL Register of Controlled Trials (CENTRAL), and the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References - carried out on 12/5/2005) were searched. Reference lists of relevant papers and major textbooks of affective disorders were checked. Experts in the field and pharmaceutical companies were contacted regarding unpublished material.

Selection criteria: 

All randomised controlled trials that compared treatment with folic acid or 5'-methyltetrahydrofolic acid to an alternative treatment, whether another antidepressant medication or placebo, for patients with a diagnosis of depressive disorder (diagnosed according to explicit criteria).

Data collection and analysis: 

Data were independently extracted from the original reports by two reviewers. Statistical analysis was conducted using Review Manager version 4.1.

Main results: 

Three trials involving 247 people were included. Two studies involving 151 people assessed the use of folate in addition to other treatment, and found that adding folate reduced Hamilton Depression Rating Scale scores on average by a further 2.65 points (95% confidence interval 0.38 to 4.93). Fewer patients treated with folate experienced a reduction in their HDRS score of less than 50% at ten weeks (relative risk (RR) 0.47, 95% CI 0.24 to 0.92) The number needed to treat with folate for one additional person to experience a 50% reduction on this scale was 5 (95% confidence interval 4 to 33). One study involving 96 people assessed the use of folate instead of the antidepressant trazodone and did not find a significant benefit from the use of folate. The trials identified did not find evidence of any problems with the acceptability or safety of folate.

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