Vitamins B₁₂, B₆, and Folic Acid for Onset of Depressive Symptoms in Older Men: Results From a 2-Year Placebo-Controlled Randomized Trial

Andrew H. Ford, M.B.B.S.; Leon Flicker, M.B.B.S., Ph.D., F.R.A.C.P.; Jenny Thomas, R.N.; Paul Norman, M.B.B.S., Ph.D., F.R.A.C.S.; Konrad Jamrozik, M.B.B.S., D.Phil.; and Osvaldo P. Almeida, M.D., Ph.D., F.R.A.N.Z.C.P.

Objective: To examine whether use of vitamins B₁₂, B₆, and folate was associated with reduced severity of depressive symptoms and 2-year incidence of clinically significant depression.

Method: The investigators recruited 299 men aged 75 years and older free of clinically significant depression (Beck Depression Inventory [BDI] score < 18). They were randomly assigned to treatment with 400 micrograms B₁₂ + 2 mg folic acid + 25 mg B₆ per day (N = 150) or placebo (N = 149). The BDI was the primary outcome measure of the study. Follow-up assessments took place 6, 12, 18, and 24 months after baseline. Analyses were intention-to-treat. The study was conducted from June 2001 to June 2004.

Results: 118 and 123 men treated with vitamins and placebo, respectively, completed this 2-year trial (19.4% dropout rate). Analysis of variance for repeated measures showed that there was no difference between the groups (F = 0.76, df = 1, p = .384) nor was there a significant change of BDI scores over time (F = 1.26, df = 4, p = .284). Cox regression revealed that participants treated with vitamins were 24% more likely to remain free of depression during the trial, although the difference between groups was not significant (95% CI = 0.68 to 2.28). At the end of the study, 84.3% of men treated with vitamins and 79.1% of those treated with placebo remained free of clinically significant depressive symptoms. The number of people needed to treat to show benefit was 21.

Conclusion: The results of this study showed that treatment with B₁₂, folic acid, and B₆ is no better than placebo at reducing the severity of depressive symptoms or the incidence of clinically significant depression over a period of 2 years in older men.

Trial Registration: www.anzctr.org.au Identifier: ACTRN012605000045617

(J Clin Psychiatry 2008;69:1203-1209. Online Ahead of Print June 10, 2008.)

Received Oct. 31, 2007; accepted Jan. 24, 2008. From South Metropolitan Health Service, Perth (Dr. Ford); the Western Australian (WA) Centre for Health and Ageing (Drs. Ford, Flicker, Norman, and Almeida and Ms. Thomas), School of Medicine and Pharmacology (Dr. Flicker), School of Surgery (Dr. Norman), and School of Psychiatry and Clinical Neurosciences (Dr. Almeida), University of Western Australia, Perth; and the School of Population Health and Clinical Practice, University of Adelaide, Adelaide (Dr. Jamrozik), Australia.

This study was supported by the National Health and Medical Research Council of Australia (project grant: 139123). The vitamin and placebo tablets were provided free of charge by Blackmores Ltd. The sponsors had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit for publication. Professor Almeida had full access to all of the data and takes responsibility for the integrity of the data and the accuracy of the data analyses.

The authors report no additional financial or other relationship relevant to the subject of this article.

Corresponding author and reprints: Osvaldo P. Almeida, M.D., WA Centre for Health & Ageing (M573), University of Western Australia, 35 Stirling Hwy., Crawley, WA 6009, Australia (e-mail: osvaldo.almeida@uwa.edu.au).