B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial

Br J Psychiatry. 2014 Dec;205(6):450-7. doi: 10.1192/bjp.bp.114.145177. Epub 2014 Sep 25.


Background: Depression is common and the efficacy of antidepressants is suboptimal. High plasma homocysteine has been consistently associated with depression, and treatment with certain B vitamins demonstrably reduces its concentration.

Aims: To determine whether vitamins B6, B12 and folic acid enhance response to antidepressant treatment over 52 weeks.

Method: Randomised, double-blind, placebo-controlled trial of citalopram (20-40 g) together with 0.5 mg of vitamin B12, 2 mg of folic acid and 25 mg of vitamin B6 for 52 weeks (Australian and New Zealand Clinical Trials Registry: 12609000256279). Participants were community-dwelling adults aged 50 years or over with DSM-IV-TR major depression. We measured severity of symptoms with the Montgomery-Åsberg Depression Rating Scale (MADRS). The primary outcome was remission of the depressive episode after 12, 26 and 52 weeks. Secondary outcomes included reduction of MADRS scores over time and relapse of major depression after recovery by week 12. Results In total, 153 people were randomised (76 placebo, 77 vitamins). Remission of symptoms was achieved by 78.1 and 79.4% of participants treated with placebo and vitamins by week 12 (P = 0.840), by 76.5 and 85.3% at week 26 and 75.8 and 85.5% at week 52 (effect of intervention over 52 weeks: odds ratio (OR) = 2.49, 95% CI 1.12-5.51). Group differences in MADRS scores over time were not significant (P = 0.739). The risk of subsequent relapse among those who had achieved remission of symptoms at week 12 was lower in the vitamins than placebo group (OR = 0.33, 95% CI 0.12-0.94).

Conclusions: B vitamins did not increase the 12-week efficacy of antidepressant treatment, but enhanced and sustained antidepressant response over 1 year. Replication of these findings would mandate that treatment guidelines adopt the adjunctive use of B vitamins as a safe and inexpensive strategy to manage major depression in middle-aged and older adults.

Publication types

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

MeSH terms

  • Aged
  • Antidepressive Agents / administration & dosage
  • Citalopram / administration & dosage*
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / drug therapy*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Drug Monitoring
  • Drug Synergism
  • Female
  • Folic Acid / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Remission Induction / methods
  • Secondary Prevention / methods
  • Time Factors
  • Treatment Outcome
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 6 / administration & dosage*
  • Vitamins / administration & dosage


  • Antidepressive Agents
  • Vitamins
  • Citalopram
  • Vitamin B 6
  • Folic Acid
  • Vitamin B 12