Effect of vitamin D supplementation on depression in older Australian adults

Sabbir T Rahman; Mary Waterhouse; Briony Duarte Romero; Catherine Baxter; Dallas R English; Osvaldo P Almeida; Michael Berk; Peter R Ebeling; Bruce K Armstrong; Donald S A McLeod; Gunter Hartel; Rachel L O'Connell; Hai Pham; James G Scott; Jolieke C van der Pols; Alison J Venn; Penelope M Webb; David C Whiteman; Rachel E Neale

doi:10.1002/gps.5847

Effect of vitamin D supplementation on depression in older Australian adults

Int J Geriatr Psychiatry. 2023 Jan;38(1):e5847. doi: 10.1002/gps.5847.

Authors

Sabbir T Rahman¹, Mary Waterhouse¹, Briony Duarte Romero¹, Catherine Baxter¹, Dallas R English^{2

3}, Osvaldo P Almeida^{4

5}, Michael Berk⁶, Peter R Ebeling⁷, Bruce K Armstrong⁸, Donald S A McLeod^{1

9}, Gunter Hartel¹, Rachel L O'Connell¹⁰, Hai Pham¹, James G Scott^{1

11}, Jolieke C van der Pols¹², Alison J Venn¹³, Penelope M Webb^{1

14}, David C Whiteman^{1

14}, Rachel E Neale^{1

14}

Affiliations

¹ Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
² Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
³ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
⁴ Medical School, University of Western Australia, Perth, Western Australia, Australia.
⁵ WA Centre for Health and Ageing of the University of Western Australia, Perth, Western Australia, Australia.
⁶ Deakin University, Institute for Mental and Physical Health and Clinical Translation (IMPACT), Barwon Health, Geelong, Victoria, Australia.
⁷ Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia.
⁸ School of Public Health, University of Sydney, Sydney, New South Wales, Australia.
⁹ Department of Endocrinology and Diabetes, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
¹⁰ NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
¹¹ Child and Youth Mental Health Service, Queensland Children's Hospital, Brisbane, Queensland, Australia.
¹² Queensland University of Technology (QUT), Faculty of Health, School of Exercise and Nutrition Sciences, Brisbane, Queensland, Australia.
¹³ Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
¹⁴ School of Public Health, the University of Queensland, Brisbane, Queensland, Australia.

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/.

Keywords: PHQ-9; antidepressants; depression; mental disorders; prevention; randomized controlled trial; vitamin D supplementation.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Australia
Cholecalciferol / adverse effects
Depression* / prevention & control
Dietary Supplements*
Double-Blind Method
Female
Humans
Male
Vitamin D
Vitamins / therapeutic use

Substances

Vitamin D
Vitamins
Cholecalciferol

Associated data

ANZCTR/ACTRN12613000743763