B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial

Ann Neurol. 2010 Oct;68(4):503-10. doi: 10.1002/ana.22189.


Objective: The consumption of certain B-vitamins through diet or supplementation decreases the total plasma concentration of homocysteine (tHcy) and may enhance response to standard antidepressant treatment. It is unclear if treatment with B-vitamins can reduce the long-term prevalence of depression in people at risk, such as stroke survivors. The purpose of this research was to determine if treatment with B-vitamins reduces the hazard of poststroke depression compared with placebo.

Methods: Randomized, double-blind, placebo-controlled trial of tHcy-lowering treatment with daily folic acid (2 mg), vitamin B6 (25 mg), and vitamin B12 (0.5 mg) for 1 to 10.5 years in survivors of stroke. The primary endpoint was the onset of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) major depression after randomization. Secondary outcomes were the prevalence of DSM-IV major or minor depression at the end of treatment. Other measured factors included age, gender, poststroke handicap associated with stroke, recurrence of strokes, cognitive impairment, and use of antidepressants.

Results: Among 273 people who completed the final assessment after 7.1 ± 2.1 years (mean ± standard deviation) of follow up, random assignment to B-vitamins was associated with a lower hazard of major depression compared with placebo (18.4% vs 23.3%, adjusted hazard ratio [HR] = 0.48; 95% confidence interval [CI] = 0.31-0.76) and a trend toward a lower odds of major or minor depression at the end of the trial compared with placebo (19.1% vs 27.7%; adjusted odds ratio [OR] = 0.58; 95%CI = 0.31-1.09).

Interpretation: Long-term treatment of poststroke survivors with folic acid, B6, and B12 was associated with a reduction in the hazard of major depression in our patient population. If these findings can be validated externally, B-vitamin supplementation offers hope as an effective, safe, and affordable intervention to reduce the burden of poststroke depression.

Trial registration: ClinicalTrials.gov NCT00097669.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Confidence Intervals
  • Depression / blood
  • Depression / diet therapy*
  • Depression / etiology*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Double-Blind Method
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Odds Ratio
  • Proportional Hazards Models
  • Retrospective Studies
  • Stroke / complications*
  • Stroke / diet therapy
  • Treatment Outcome
  • Vitamin B Complex / blood
  • Vitamin B Complex / therapeutic use*


  • Vitamin B Complex

Associated data

  • ClinicalTrials.gov/NCT00097669