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Can Vitamin D Supplementation Benefit People With Early Psychosis?

  • Authors: News Author: Megan Brooks; CME Author: Charles P. Vega, MD
  • CME / ABIM MOC / CE Released: 2/18/2022
  • Valid for credit through: 2/18/2023, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for primary care physicians, mental health specialists, nurses, pharmacists and other members of the healthcare team who treat and manage patients with a history of psychosis.

The goal of this activity is to evaluate the efficacy of vitamin D supplements among adults with a history of recent psychosis.

Upon completion of this activity, participants will:

  • Distinguish why adults with psychosis have a higher risk for vitamin D deficiency
  • Evaluate outcomes improved with vitamin D supplementation among adults with a first episode of psychosis
  • Outline implications for the healthcare team


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News Author

  • Megan Brooks

    Freelance writer, Medscape


    Disclosure: Megan Brooks has disclosed no relevant financial relationships.

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine
    Irvine, California


    Disclosure: Charles P. Vega, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: GlaxoSmithKline; Johnson & Johnson

Editor/CME Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance
    Medscape, LLC


    Disclosure: Amanda Jett, PharmD, BCACP, has disclosed no relevant financial relationships.

CME/CE Reviewer/Nurse Planner

  • Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC


    Disclosure: Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP, has disclosed no relevant financial relationships.

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Can Vitamin D Supplementation Benefit People With Early Psychosis?

Authors: News Author: Megan Brooks; CME Author: Charles P. Vega, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 2/18/2022

Valid for credit through: 2/18/2023, 11:59 PM EST


Clinical Context

Vitamin D deficiency has been scrutinized among people who have experienced psychosis, and the authors of the current study explain that vitamin D deficiency is more common in cases of psychosis compared with the general population. This phenomenon is thought to be related to reversible lifestyle issues such as more sedentary lifestyles, less sun exposure, and worse nutrition vs a pathological process directly related to psychosis or its treatment.

Routine cases of vitamin D deficiency do not cause brain dysfunction, but persons with vitamin D deficiency might have a worse prognosis for neurologic illness. A trial of vitamin D supplementation among patients with Parkinson disease demonstrated that active treatment reduced the risk for progression vs placebo. However, a trial of weekly vitamin D dosing failed to demonstrate a benefit vs placebo among patients with treatment-resistant schizophrenia.

This previous trial lasted only 8 weeks and included adults with chronic schizophrenia. The current placebo-controlled trial tested vitamin D supplementation among patients after their first episode of psychosis, when such treatment might have a greater chance to be effective.

Study Synopsis and Perspective

Low vitamin D is common in patients with first-episode psychosis (FEP), but supplementation does not appear to improve mental or physical symptoms, new data show.

"Previous work, our own and others, has shown that people with psychosis, even soon after their first diagnosis, have low vitamin D levels, but it was not known whether supplementing with vitamin D in people with early psychosis would improve health outcomes," study investigator Fiona Gaughran, MD, with the Institute of Psychiatry, Psychology & Neuroscience, King's College London, United Kingdom, told Medscape Medical News.

"While we did not demonstrate a benefit of supplementation over 6 months, these very high rates of vitamin deficiency and insufficiency may have longer-term negative health impacts which we have not measured, so raising awareness of the need to optimize vitamin D in people with psychosis is important," said Dr Gaughran.

The results of the randomized clinical trial were published online December 28 in JAMA Network Open.

Thoughtful Approach, Negative Result

Participants included 149 adults within 3 years of a first presentation with a functional psychotic disorder. The cohort's mean age was 28 years, 60% were men, 44% were Black or of other racial and ethnic minority group, and 56% were White.

Seventy-five participants were randomly assigned to receive 120,000 IU of cholecalciferol or matching placebo administered by the researchers in monthly doses with an oral syringe.

"We chose a dose of 120,000 IU monthly (equivalent to 4000 IU daily), which was expected to safely increase vitamin D levels. The regimen was discussed with experts with lived experience and took into account that a daily preparation would add to the significant medication load that people with psychosis already carry," said Dr Gaughran.

Vitamin D supplementation as administered in this study was safe and led to a significant increase in 25-hydroxyvitamin D concentrations.

However, there was no significant difference between vitamin D and placebo in the primary outcome of total Positive and Negative Syndrome Scale (PANSS) score at 6 months (mean difference, 3.57; 95% confidence interval, −1.11 to 8.25; P=.13).

There was also no apparent benefit of vitamin D supplementation on any secondary outcome, including the PANSS subscores of global function and depression or cardiometabolic risk factors.

"With respect to clinical practice, we cannot now recommend monthly treatments with 120 000 IU of cholecalciferol in FEP," the investigators note.

The prevalence of vitamin D insufficiency and deficiency was high in the population, at 74.6% overall and 93.4% among ethnic minorities.

"[T]hus, the sample was well suited to detecting any potential benefits that may have arisen from correcting this. However, even in this subgroup, there was no evidence to support the guiding hypothesis" that vitamin D supplementation would improve outcomes in patients with early psychosis, the researchers note.

They suggest that future studies examine the association of vitamin D with brain-related outcomes based on periods of treatment longer than 6 months and administered as daily rather than bolus treatments.

"Future public health strategies should acknowledge the high prevalence of vitamin D insufficiency and deficiency in people with psychosis and consider any reasonable adjustments which may be needed to address this over and above general population guidance," said Dr Gaughran.

The study was funded by the Stanley Medical Research Institute and received support from the National Institute for Health Research Maudsley Biomedical Research Centre, King's College London and the National Institute for Health Research Applied Research Collaboration South London. Dr Gaughran reported receiving speaking honoraria from Otsuka Lundbeck outside the submitted work. A complete list of author disclosures is available with the original article.

JAMA Netw Open. Published online December 28, 2021.[1]

Study Highlights

  • Study participants were adults living in the United Kingdom who were between 18 and 65 years of age. All participants had a first psychotic episode within the past 3 years. Patients with a potential serious disorder affecting vitamin D metabolism or who used medications that might cause vitamin D deficiency were excluded from the study.
  • Study participants were randomly assigned to receive 120,000 IU oral vitamin D3 weekly or matching placebo. The treatment period was 6 months.
  • The main study outcome was the PANSS at 6 months. Researchers also examined the PANSS score at 3 months, a general survey of mental health symptoms, a global assessment of function, a depression survey, and a number outcomes related to metabolism and body weight.
  • 835 patients were approached for study entry and 149 adults enrolled in the study. The mean age of participants was 28.1 years, 59.7% were male, 43.6% were Black, and 56.4% were White.
  • 53 participants had schizophrenia or schizoaffective disorder and 55 had other nonorganic psychosis.
  • 74.6% of participants had 25-OH-D levels less than 20 ng/mL at baseline, with 40.9% with levels less than 10 ng/mL. Vitamin D deficiency was more common among Black participants.
  • Baseline characteristics were well-matched in the vitamin D supplement and placebo cohorts.
  • Vitamin D supplementation was associated with an average increase in 25-OH-D levels of 16 ng/mL over the course of 6 months. 25-OH-D levels remained stable in the placebo group.
  • There was no difference in the PANSS score at 3 or 6 months in comparing the placebo and vitamin D group or in an analysis that focused on positive or negative symptoms specifically. Scores for general psychopathology and a global assessment of function were also similar between groups.
  • There was also no difference in the following outcomes in comparing the vitamin D supplement and placebo groups at 6 months:
    • Body mass index
    • Waist circumference
    • HbA1c level
    • Total cholesterol level
    • C-reactive protein level
  • Vitamin D supplements remained ineffective across multiple outcomes in a subgroup analysis based on participants with baseline vitamin D deficiency.
  • Adverse events were reported in 2.7% of the vitamin D group and 4.0% of the placebo cohort.

Clinical Implications

  • Vitamin D deficiency is more common in cases of psychosis compared with the general population. This phenomenon is thought to be related to reversible lifestyle issues such as more sedentary lifestyles, less sun exposure, and worse nutrition vs a pathological process directly related to psychosis or its treatment.
  • In the current study, vitamin D supplements did not improve mental health outcomes among patients with a first episode of psychosis. Vitamin D supplements were also not effective in improving function, body mass index, HbA1c, and total cholesterol values. Vitamin D supplements did raise 25-OH-D levels vs placebo.
  • Implications for the healthcare team: The healthcare team should not recommend vitamin D supplements to improve the course of illnesses featuring psychosis.


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