Effect of vitamin D supplementation on depression in older Australian adults

OBJECTIVES: To investigate whether vitamin D supplementation reduces depressive symptoms and incidence of antidepressant use. METHODS: We used data from the D‐Health Trial (N = 21,315), a randomized double‐blind placebo‐controlled trial of monthly vitamin D(3) for the prevention of all‐cause mortality. Participants were Australians aged 60–84 years. Participants completed the Patient Health Questionnaire (PHQ–9) at 1, 2 and 5 years after randomization to measure depressive symptoms; national prescribing records were used to capture antidepressant use. We used mixed models and survival models. RESULTS: Analyses of PHQ‐9 scores included 20,487 participants (mean age 69·3 years, 46% women); the mean difference (MD) in PHQ‐9 score (vitamin D vs. placebo) was 0·02 (95% CI −0·06, 0·11). There was negligible difference in the prevalence of clinically relevant depression (PHQ‐9 score ≥10) (odds ratio 0·99; 95% CI 0·90, 1·08). We included 16,670 participants in the analyses of incident antidepressant use (mean age 69·4 years, 43% women). Incidence of antidepressant use was similar between the groups (hazard ratio [HR] 1·04; 95% CI 0·96, 1·12). In subgroup analyses, vitamin D improved PHQ‐9 scores in those taking antidepressants at baseline (MD −0·25; 95% CI −0·49, −0·01; p‐interaction = 0·02). It decreased risk of antidepressant use in participants with predicted 25(OH)D concentration <50 nmol/L (HR 0·88; 95% CI 0·75, 1·02; p‐interaction = 0·01) and increased risk in those with predicted 25(OH)D ≥ 50 nmol/L (HR 1·10; 95% CI 1·01, 1·20). CONCLUSION: Monthly supplementation with high‐dose vitamin D(3) was not of benefit for measures of depression overall, but there was some evidence of benefit in subgroup analyses. CLINICAL TRIAL REGISTRATION: The trial is registered on the Australian New Zealand Clinical Trials Registry: ACTRN12613000743763. https://www.anzctr.org.au/.