Hostname: page-component-8678677fb7-z882p Total loading time: 0 Render date: 2026-10-13T18:35:46.198Z Has data issue: false hasContentIssue false
  • English
  • Français

Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression

Published online by Cambridge University Press:  03 February 2015

Osvaldo P. Almeida ,
Andrew H. Ford  and
Leon Flicker
Osvaldo P. Almeida*
Affiliation:
WA Centre for Health & Ageing, University of Western Australia, Crawley, WA, Australia School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia Department of Psychiatry, Royal Perth Hospital, Perth, WA, Australia
Andrew H. Ford
Affiliation:
WA Centre for Health & Ageing, University of Western Australia, Crawley, WA, Australia School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia Department of Psychiatry, Royal Perth Hospital, Perth, WA, Australia
Leon Flicker
Affiliation:
WA Centre for Health & Ageing, University of Western Australia, Crawley, WA, Australia School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, Australia Department of Geriatric Medicine, Royal Perth Hospital, Perth, WA, Australia
*
Correspondence should be addressed to: Osvaldo P. Almeida, Professor, WA Centre for Health & Ageing (M573), University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia. Phone: +61-8-9224 2855. Email: osvaldo.almeida@uwa.edu.au.
Get access

Abstract

Background:

Folate and vitamin B12 insufficiencies have been associated with increased risk of depression. This systematic review aimed to clarify if, compared with placebo, treatment with folate and/or vitamin B12 reduces depression scale scores, increases remission, and prevents the onset of clinically significant symptoms of depression in people at risk.

Methods:

This systematic review searched the PubMed, PsychInfo, Embase, and Cochrane databases from inception to 6 June 2014, using the following terms and strategy: (vitamin B12 or vitamin B9 or folate or folic acid or cobalamin or cyanocobalamin) and (depression or depressive disorder or depressive symptoms) and (randomized controlled trial or RCT). The electronic search was supplemented by manual search. Two independent reviewers assessed all papers retrieved for eligibility and bias, and extracted crude data. Review Manager 5 was used to manage and analyze the data.

Results:

Two hundred and sixty-nine manuscripts were identified, of which 52 were RCTs and 11 fulfilled criteria for review. We found that the short-term use of vitamins (days to a few weeks) does not contribute to improve depressive symptoms in adults with major depression treated with antidepressants (5 studies, standardized mean difference = −0.12, 95% confidence interval – 95% CI = −0.45, 0.22), but more prolonged consumption (several weeks to years) may decrease the risk of relapse (1 study, odds ratio (OR) = 0.33, 95% CI = 0.12, 0.94) and the onset of clinically significant symptoms in people at risk (2 studies, risk ratio = 0.65, 95% CI = 0.43, 0.98).

Conclusions:

The number of available trials remains small and heterogeneity between studies high. The results of these meta-analyses suggest that treatment with folate and vitamin B12 does not decrease the severity of depressive symptoms over a short period of time, but may be helpful in the long-term management of special populations.

Keywords

depressiondepressive symptomsdepressive disordervitamin B12folic acidfolatemethylfolatevitamin B9vitamin B6treatmentefficacyrandomized controlled trial

Information

Type
Review Article
Information
International Psychogeriatrics , Volume 27 , Issue 5 , May 2015 , pp. 727 - 737
Copyright
Copyright © International Psychogeriatric Association 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Almeida, O. P. (2014). Prevention of depression in older age. Maturitas, 79, 136–141.Google Scholar
Almeida, O. P., Marsh, K., Alfonso, H., Flicker, L., Davis, T. M. and Hankey, G. J. (2010). B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial. Annals of Neurology, 68, 503–510.CrossRefGoogle ScholarPubMed
Almeida, O. P., McCaul, K., Hankey, G. J., Norman, P., Jamrozik, K. and Flicker, L. (2008). Homocysteine and depression in later life. Archives of General Psychiatry, 65, 1286–1294.Google Scholar
Almeida, O. P. et al. (2014). B-vitamins to enhance treatment response to antidepressants in mid and late life: results from the B-VITAGE randomised, double-blind, placebo-controlled trial. British Journal of Psychiatry, 205, 450–457.Google Scholar
Bottiglieri, T. (2005). Homocysteine and folate metabolism in depression. Progress in Neuropsychopharmacology and Biological Psychiatry, 29, 1103–1112.Google Scholar
Carney, M. W. (1967). Serum folate values in 423 psychiatric patients. British Medical Journal, 4, 512–516.Google Scholar
Coppen, A. and Bailey, J. (2000). Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. Journal of Affective Disorders, 60, 121–130.Google Scholar
Coppen, A., Chaudhry, S. and Swade, C. (1986). Folic acid enhances lithium prophylaxis. Journal of Affective Disorders, 10, 9–13.Google Scholar
Ford, A. H., Flicker, L., Thomas, J., Norman, P., Jamrozik, K. and Almeida, O. P. (2008). Vitamins B12, B6, and folic acid for onset of depressive symptoms in older men: results from a 2-year placebo-controlled randomized trial. Journal of Clinical Psychiatry, 69, 1203–1209.Google Scholar
Gilbody, S., Lightfoot, T. and Sheldon, T. (2007). Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity. Journal of Epidemiology and Community Health, 61, 631–637.Google Scholar
Godfrey, P. S. et al. (1990). Enhancement of recovery from psychiatric illness by methylfolate. Lancet, 336, 392–395.Google Scholar
Higgins, J. P., Thompson, S. G., Deeks, J. J. and Altman, D. G. (2003). Measuring inconsistency in meta-analyses. British Medical Journal, 327, 557–560.Google Scholar
Higgins, J. P. T. and Green, S. (2011). Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0: The Cochrane Collaboration. Available at: http://www.cochrane-handbook.org.Google Scholar
Holmes, M. V. et al. (2011). Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet, 378, 584–594.Google Scholar
Hvas, A. M., Juul, S., Lauritzen, L., Nexo, E. and Ellegaard, J. (2004). No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study. Journal of Affective Disorders, 81, 269–273.Google Scholar
Loria-Kohen, V., Gomez-Candela, C., Palma-Milla, S., Amador-Sastre, B., Hernanz, A. and Bermejo, L. M. (2013). A pilot study of folic acid supplementation for improving homocysteine levels, cognitive and depressive status in eating disorders. Nutricion Hospitalaria, 28, 807–815.Google Scholar
Papakostas, G. I. et al. (2012). L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. American Journal of Psychiatry, 169, 1267–1274.Google Scholar
Passeri, M. et al. (1993). Oral 5¢-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study. Aging (Milano), 5, 63–71.Google Scholar
Resler, G. et al. (2008). Effect of folic acid combined with fluoxetine in patients with major depression on plasma homocysteine and vitamin B12, and serotonin levels in lymphocytes. Neuroimmunomodulation, 15, 145–152.Google Scholar
Reynolds, E. H., Preece, J. M., Bailey, J. and Coppen, A. (1970). Folate deficiency in depressive illness. British Journal of Psychiatry, 117, 287–292.Google Scholar
Shorvon, S. D., Carney, M. W., Chanarin, I. and Reynolds, E. H. (1980). The neuropsychiatry of megaloblastic anaemia. British Medical Journal, 281, 1036–1038.CrossRefGoogle ScholarPubMed
Taylor, M. J., Carney, S., Geddes, J. and Goodwin, G. (2003). Folate for depressive disorders. Cochrane Database Systematic Reviews, Cd003390.Google Scholar
Taylor, M. J., Carney, S. M., Goodwin, G. M. and Geddes, J. R. (2004). Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials. Journal of Psychopharmacology, 18, 251–256.Google Scholar
VITATOPS (2010). B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. Lancet Neurology, 9, 855–865.Google Scholar
Walker, J. G. et al. (2010). Mental health literacy, folic acid and vitamin B12, and physical activity for the prevention of depression in older adults: randomised controlled trial. British Journal of Psychiatry, 197, 45–54.Google Scholar
Walker, J. G. et al. (2012). Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms–the Beyond Ageing Project: a randomized controlled trial. American Journal of Clinical Nutrition, 95, 194–203.CrossRefGoogle ScholarPubMed
Supplementary material: File

Almeida supplementary material

List of References

Download Almeida supplementary material(File)
File 177.4 KB
Supplementary material: File

Almeida supplementary material

Figures S1-S2

Download Almeida supplementary material(File)
File 243.9 KB