Plain language summary
Depression can considerably impair daily function. However, although medications and psychological therapy can be effective in treating depression, non‐compliance with and/or side effects of antidepressants are common. Thus, identifying alternative or adjunctive therapies to prevent or treat depression may help to overcome some limitations of current management strategies. The aim of this study was to examine whether supplementing older Australians with monthly doses of 60,000 IU of vitamin D3 for 5 years would reduce depressive symptoms or incidence of antidepressant use, as a surrogate for a formal diagnosis of depression. This study used data from the D‐Health Trial, a large population‐based randomised controlled trial. Authors randomly selected potential participants aged between 60 and 79 years from the Australian Commonwealth Electoral Roll. The participants who accepted the invitation were randomly allocated to either 60,000 IU of cholecalciferol (vitamin D3) or placebo in a 1:1 ratio. Results show that there wasn’t an overall benefit of monthly supplementation with 60,000 IU of vitamin D for up to 5 years on measures of depression. However, pre‐specified subgroup analyses suggested a potential beneficial effect of vitamin D supplementation in people taking antidepressants at baseline or with lower predicted baseline vitamin D3 concentration. However there was an unfavourable effect in participants with a body mass index <25 kg/m2 or those with higher predicted baseline vitamin D3 concentration. Authors conclude that routine supplementation with vitamin D in populations with a low prevalence of vitamin D deficiency is unlikely to be of benefit for depression and may cause harm in people with low body mass index or normal vitamin D status.
Abstract
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 D3 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 D3 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/.
Methodological quality
Jadad score
:
5
Allocation concealment
:
Yes
