Abstract
People with psychotic disorders have an increased risk of vitamin D deficiency, which is evident during first-episode psychosis (FEP) and associated with unfavorable mental and physical health outcomes. To examine whether vitamin D supplementation contributes to improved clinical outcomes in FEP. This multisite, double-blind, placebo-controlled, parallel-group randomized clinical trial from the UK examined adults 18 to 65 years of age within 3 years of a first presentation with a functional psychotic disorder who had no contraindication to vitamin D supplementation. A total of 2136 patients were assessed for eligibility, 835 were approached, 686 declined participation or were excluded, 149 were randomized, and 104 were followed up at 6 months. The study recruited participants from January 19, 2016, to June 14, 2019, with the final follow-up (after the last dose) completed on December 20, 2019. Monthly augmentation with 120 000 IU of cholecalciferol or placebo. The primary outcome measure was total Positive and Negative Syndrome Scale (PANSS) score at 6 months. Secondary outcomes included total PANSS score at 3 months; PANSS positive, negative, and general psychopathology subscale scores at 3 and 6 months; Global Assessment of Function scores (for symptoms and disability); Calgary Depression Scale score, waist circumference, body mass index, and glycated hemoglobin, total cholesterol, C-reactive protein, and vitamin D concentrations at 6 months; and a planned sensitivity analysis in those with insufficient vitamin D levels at baseline. A total of 149 participants (mean [SD] age, 28.1 (8.5) years; 89 [59.7%] male; 65 [43.6%] Black or of other minoritized racial and ethnic group; 84 [56.4%] White [British, Irish, or of other White ethnicity]) were randomized. No differences were observed in the intention-to-treat analysis in the primary outcome, total PANSS score at 6 months (mean difference, 3.57; 95% CI, -1.11 to 8.25; P = .13), or the secondary outcomes at 3 and 6 months (PANSS positive subscore: mean difference, -0.98; 95% CI, -2.23 to 0.27 at 3 months; mean difference, 0.68; 95% CI, -0.69 to 1.99 at 6 months; PANSS negative subscore: mean difference, 0.68; 95% CI, -1.39 to 2.76 at 3 months; mean difference, 1.56; 95% CI, -0.31 to 3.44 at 6 months; and general psychopathology subscore: mean difference, -2.09; 95% CI, -4.36 to 0.18 at 3 months; mean difference, 1.31; 95% CI, -1.42 to 4.05 at 6 months). There also were no significant differences in the Global Assessment of Function symptom score (mean difference, 0.02; 95% CI, -4.60 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. Vitamin D levels were very low in the study group, especially in Black participants and those who identified as another minoritized racial and ethnic group, 57 of 61 (93.4%) of whom had insufficient vitamin D. The treatment was safe and led to a significant increase in 25-hydroxyvitamin D concentrations. In this randomized clinical trial, no association was found between vitamin D supplementation and mental health or metabolic outcomes at 6 months. Because so few patients with FEP were vitamin D replete, the results of this study suggest that this group would benefit from active consideration in future population health strategies. isrctn.org Identifier: ISRCTN12424842.
Highlights
There were no significant differences in the Global Assessment of Function symptom score; Global Assessment of Function disability score, or Calgary Depression Scale score
The treatment was safe and led to a significant increase in 25-hydroxyvitamin D concentrations. In this randomized clinical trial, no association was found between vitamin D supplementation and mental health or metabolic outcomes at 6 months
Because so few patients with first-episode psychosis (FEP) were vitamin D replete, the results of this study suggest that this group would benefit from active consideration in future population health strategies
Summary
Vitamin D deficiency is more common in people with psychosis than in the general population.[1,2,3,4] The concentration of 25-hydroxyvitamin D, the transport and storage form of vitamin D commonly used to assess overall vitamin D status, is low in many chronic mental and general medical conditions, including psychosis.[5,6] This finding is thought to result from poor general health associated with sedentary lifestyles, less sun exposure, and poor general nutrition.[7]Animal experiments have linked low vitamin D with changes in brain-related outcomes,[3,8,9] triggering speculation that vitamin D supplementation may improve such outcomes[10] and that vitamin D may be neuroprotective.[11]. Variants in the CACNA1C gene (OMIM 114205), which encodes an L-type calcium channel subunit, confer an increased risk of schizophrenia.[14,15]
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