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.

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]

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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