Vitamin D Not Impactful Against Late-Life Depression

Low levels of 25-hydroxyvitamin D has been linked in the past to a higher risk of later life depression. However, there have been very few long-term, high-dose large-scale trials testing this principal.

Olivia I. Okereke, MD, SM

A team, led by Olivia I. Okereke, MD, SM, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, tested the effects of vitamin D3 supplementation on late-life depression risk and mood scores.

In the randomized clinical trial dubbed the VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention), the investigators examined 18,353 individuals older than 50.

In VITAL-DEP, 16,657 individuals were at risk of incident depression with no depression history and 1696 participants were at risk for recurrent depression with a history of depression, but no treatment for depression within the past 2 years.

The mean age of the patient population was 67.5 years old, the median treatment duration was 5.3 years, and 90.5% of the participants completed the trial—93.5% of those alive at the conclusion of the trial.

The investigators used a 2 x 2 factorial design to randomize patients to either vitamin D3 (2000 IU/d of cholecalciferol) and fish oil (n = 9181) or placebo (n = 9172).

The investigators sought primary outcomes of the risk of depression or clinically relevant depressive symptoms defined as the total of incident and recurrent cases, as well as the mean difference in mood scores based on the 8-item Patient Health Questionnaire depression scale (PHQ-8) [score range, 0 points [least symptoms] to 24 points [most symptoms]; the minimal clinically important difference for change in scores was 0.5 points).

The investigators found the risk of depression or clinically relevant depressive symptoms was not significantly different between the vitamin D3 group (609 depression or clinically relevant depressive symptom events; 12.9/1000 person-years) and the placebo group (625 depression or clinically relevant depressive symptom events; 13.3/ 1000 person-years) (HR, 0.97; 95% CI, 0.87-1.09; P = 0.62).

The researchers did not find significant differences between groups in depression incidence or recurrence or between treatment groups for changes in mood scores over time. The mean change in PHQ-8 score was not significantly different from zero (mean difference for change in mood scores, 0.01 points; 95% CI, -0.04 to 0.05 points).

“Among adults aged 50 years or older without clinically relevant depressive symptoms at baseline, treatment with vitamin D3 compared with placebo did not result in a statistically significant difference in the incidence and recurrence of depression or clinically relevant depressive symptoms or for change in mood scores over a median follow-up of 5.3 years,” the authors wrote. “These findings do not support the use of vitamin D3 in adults to prevent depression.”

The study, “Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores,” was published online in JAMA.