Vitamin D supplementation not tied to mental health outcomes in first-episode psychosis

Vitamin D supplementation did not appear linked to mental health or metabolic outcomes at 6 months in people with first-episode psychosis, according to results of a randomized clinical trial published in JAMA Network Open.

“We report the results of the DFEND (Vitamin D Supplementation Compared to Placebo in People With First Episode Psychosis–Neuroprotection Design) trial,” Fiona Gaughran, MD, of the department of psychosis studies at King’s College London’s Institute of Psychiatry, Psychology and Neuroscience in the U.K., and colleagues wrote. “We hypothesized that, compared with placebo, patients with [first-episode psychosis] receiving vitamin D supplementation would have a greater reduction in Positive and Negative Syndrome Scale (PANSS) scores over time, with the PANSS subscores of global function and depression selected as secondary outcomes. Finally, reflecting evidence of the association between neuroprogression and somatoprogression and the associations among vitamin D deficiency, medical conditions, and mental disorders (eg, obesity, diabetes, and hypercholesterolemia), we included a range of biomarkers as secondary outcomes.”

The researchers randomly assigned 149 adults (mean age, 28.1 years; 59.7% men) from the U.K. aged 18 to 65 years within 3 years of a first presentation of a functional psychotic disorder who did not have a contraindication to vitamin D supplementation. They received follow-up data from 104 participants at 6 months. The intervention consisted of monthly augmentation with 120,000 IU of cholecalciferol or placebo. Total PANSS score at 6 months served as the primary outcome and total PANSS score at 3 months as a secondary outcome. Additional secondary outcomes included PANSS positive, negative and general psychopathology subscale score at 3 and 6 months, Global Assessment of Function scores for symptoms and disability, Calgary Depression Scale score, wait circumference, BMI and 6-month concentrations of glycated hemoglobin, total cholesterol, C-reactive protein and vitamin D. They also conducted a planned sensitivity analysis among individuals with insufficient baseline vitamin D levels.

Results showed no differences in the intention-to-treat analysis for total PANSS score at 6 months (mean difference, 3.57; 95% CI, 1.11 to 8.25) or the secondary outcomes at 3 and 6 months. Further, Gaughran and colleagues observed no significant differences in the Global Assessment of Function symptom score (mean difference, 0.02; 95% CI, 4.6 to 4.94), Global Assessment of Function disability score (mean difference, 0.01; 95% CI, 5.25 to 5.23) or Calgary Depression Scale score (mean difference, 0.39; 95% CI, 2.05 to 1.26) at 6 months. The study group had significantly low vitamin D levels, particularly Black participants and those who identified as another underrepresented racial or ethnic group. The researchers noted the treatment’s safety and that it significantly increased 25-hydroxyvitamin D concentrations.

“Despite considerable public interest in the association between vitamin D and diverse health outcomes, the results from RCTs have deflated these expectations,” Gaughran and colleagues wrote. “The findings of the current study similarly do not provide evidence that vitamin D supplementation for 6 months shows benefit in the treatment of [first-episode psychosis] but highlight that only a few individuals in this group are vitamin D replete and thus may benefit from particular attention in any future public health strategies.”