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

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