No clear potentiation of antidepressant medication effects by folic acid+vitamin B12 in a large community sample

J Affect Disord. 2011 Apr;130(1-2):37-45. doi: 10.1016/j.jad.2010.07.029.

Abstract

Background: Observational studies link low folate levels to depressive symptoms and to poor antidepressant medication response. Evidence supports a role for folate in potentiating the effect of antidepressant medications.

Aim: This prospective study examines the effects of folic acid+vitamin B12 supplementation and antidepressant medication in a community-based study of older adults with depressive symptoms.

Method: A randomised controlled trial investigated the effectiveness of a medicinal and two behavioural preventive interventions over a two year period. The medicinal intervention compared dietary supplementation of 400 mcg/d folic acid+100 mcg/d vitamin B12 to placebo. Self reported use of antidepressant medication over two years was recorded. Participants were screened for psychological distress using the Kessler Distress 10-Scale (K-10; >15 eligible) and the main outcome measure was change in depressive symptoms on the Patient Health Questionnaire-9 (PHQ-9) at six weeks, six, 12 and 24 months. Nine hundred adults aged 60-74 years were included in the analysis, of whom 209 (23.2%) reported antidepressant use during the follow-up period.

Results: A mixed model repeated measures analysis of variance for reduction in depressive symptoms found no significant three-way interaction between supplement group and antidepressant use over time on the PHQ-9 [F4, 825.1=0.32, p=0.87]. A small interaction between supplement group and antidepressant use over time was found for K-10 scores (F4, 799.5=2.50, p=0.0414).

Conclusions: There was little evidence for the potentiation of antidepressant medication by folic acid+B12 supplementation on depressive symptomatology. Further research should examine whether effects might be found at higher folic acid dosages or among clinical populations.

Trial registration: ClinicalTrials.gov NCT00214682.

Publication types

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

MeSH terms

  • Aged
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / therapeutic use*
  • Depressive Disorder / drug therapy*
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Folic Acid / administration & dosage
  • Folic Acid / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Surveys and Questionnaires
  • Treatment Outcome
  • Vitamin B 12 / administration & dosage
  • Vitamin B 12 / therapeutic use*
  • Vitamins / adverse effects
  • Vitamins / therapeutic use*

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00214682