No clear potentiation of antidepressant medication effects by folic acid + vitamin B 12 in a large community sample

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.