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.

Randomized, double-blind, placebo-controlled trial in community-dwelling adults aged 50 years or older with DSM-IV-TR major depressive disorder in the Perth metropolitan region of Australia. In the active vitamins group, 77 participants were randomized; 73 completed week 12, 68 completed week 26, and 62 completed week 52.

An oral daily capsule of vitamin B12 0.5 mg, folic acid 2 mg, and vitamin B6 25 mg was given as adjunctive treatment to citalopram after breakfast for 52 weeks, compared with placebo. The regimen was tested in the active vitamins arm.

Adjunctive B vitamins did not improve the primary 12-week remission outcome, but they were associated with better sustained antidepressant response over 52 weeks and fewer relapses among those remitted by week 12. Remission at week 12 was 79.4% with vitamins versus 78.1% with placebo (p = 0.840), while remission over 52 weeks favored vitamins with an odds ratio of 2.49 (1.12-5.51). Relapse after week-12 remission was lower with vitamins, with an odds ratio of 0.33 (0.12-0.94), and the reduction in MADRS scores over time was not significant between groups (p = 0.739). Benefits were more evident in participants with higher baseline homocysteine.

The primary short-term outcome was null, and the trial had a modest sample size with attrition over 52 weeks, which limits precision. Findings on longer-term benefit and relapse prevention may be less certain because they depend on completers and adjusted analyses, and generalizability is limited to older adults receiving citalopram in one Australian metropolitan setting.