For individuals diagnosed with depression, is the supplementation of folate, B6 or B12 in any combination, effective at improving depressive symptoms, when used either in isolation, or as an adjunctive therapy, compared to antidepressant medication alone?
By Sam Dunkley - MSc in Nutritional Therapy
Abstract
Background
The number of people suffering from depression worldwide is increasing and this can be a serious and debilitating health condition. Conventional treatment for clinical depression is based primarily upon the use of antidepressant medication, which for certain individuals can be ineffective and cause unwanted side effects. A number of studies have been conducted into the efficacy of alternative and adjunctive therapies, to aid in the improvement of depressive symptoms, either as stand-alone treatments, or in combination with current antidepressant medication. This review investigates the role of the methyl donor B vitamins (B6, folate and B12) and their effectiveness in this capacity.
Aim
To determine whether the supplementation of vitamins B6, folate, or B12 in any combination, is effective at improving depressive symptoms, for individuals diagnosed with depression; when used either in isolation, or as an adjunctive therapy, compared to antidepressant medication alone.
Methodology
Searches were conducted of AMED, CENTRAL, CINAHL, EMBASE, PsycINFO, and PubMed from January 2015–April 2015, in addition to ClinicalTrials.gov, in order to identify any ongoing trials in this area. Reference lists of citations were also checked for additional Randomised Controlled Trials (RCTs) and study authors contacted. As RCTs are considered the gold standard of study design for answering questions about the effect of an intervention, the specific selection criteria was set to identify RCTs, comparing treatment with vitamin B6, folate or B12 to antidepressant medication or placebo, for individuals diagnosed with depression. Trial quality was assessed using the Cochrane RoB tool and data extracted by the study author into an Excel spreadsheet and Review Manager 5 for analysis.
Main results
Eleven trials comprising 1177 participants were included. Seven of these involving 961 individuals, studied folate as an adjunctive therapy to antidepressants and were all placebo controlled. An overall standardised mean difference of -0.47 was observed (95% CI -0.85 to-0.08), with data favouring the intervention and achieving statistical significance, but presenting substantial heterogeneity. Two trials containing 211 participants, studied vitamin B12 as an adjunctive therapy, presenting an overall standardised mean difference of -0.28 (95% CI -0.56 to 0.00), with data again favouring the intervention, but this effect was not statistically significant.
Conclusions
The studies included within this review displayed substantial heterogeneity between them, when combined for a meta-analysis and therefore, conclusions could not be derived from the pooled estimates of effect. Future trials should aim to be more consistent with the dosage and duration of the intervention used with respect to other RCTs in this area. In addition, stratifying for age, gender, ethnicity, nutritional and socioeconomic status, as well as genetic Single Nucleotide Polymorphisms (SNPs), should be considered in order to lessen the potential for heterogeneity between studies.
