Effect of a six-month vitamin D supplementation on depressive symptoms in patients with major depressive episode (DepFuD): a double-blinded randomised controlled trial

BACKGROUND: Initial studies suggest vitamin D (VD) supplementation may aid in treating major depressive disorder, but rigorous randomised controlled trials are needed. TRIAL DESIGN: DepFuD trial was a six-month, double-blinded, parallel-group, randomised controlled superiority design trial with a 1:1 allocation ratio. Outpatients with mild to severe depression episode, aged 18-65 years, were included. METHODS: The primary aim was to compare the effects of low-dose versus high-dose VD as adjunctive to participants' existing depression treatments, hypothesising that the high-dose group would show greater symptom reduction over six months. Participants were randomised to receive either 100 μg (4000 IU) or 10 μg (400 IU) of VD (cholecalciferol) daily for six months. The primary outcome was measured by between-group differential change over six months in the Montgomery-Åsberg Depression Rating Scale (MADRS) score (range: 0-60). Data was collected in Finland between November 2015 and December 2020. RESULTS: A total of 281 participants were randomised: 142 in the low-dose and 139 in the high-dose group. At baseline, 46% of the participants in low-dose and 42% in high-dose group had VD deficiency (<50 nmol/l). Primary outcome data were available for 234 participants (116 in low-dose and 118 in high-dose). The standardised adjusted MADRS mean difference was small and non-significant (Cohen's d = -0.09; 95% CI -0.32 to 0.14). CONCLUSIONS: The six-month trial demonstrated no superior effect of the higher VD supplementation compared to the lower VD supplementation on depressive symptoms. REGISTRATION: ClinicalTrials.gov: NCT02521012. DepFuD was supported by Finnish State Research Funding (VTR).