Vitamin D Supplementation in Chronic Schizophrenia Patients Treated with Clozapine: A Randomized, Double-Blind, Placebo-controlled Clinical Trial

Abstract

BackgroundWhile accumulating evidence suggests that vitamin D deficiency may be involved in the risk to develop schizophrenia and its outcome, there are no studies on vitamin D supplementation in this context. We sought to assess the effect of vitamin D supplementation on psychiatric, cognitive and metabolic parameters in chronic clozapine-treated schizophrenia patients.MethodsThis eight-week, randomized, double-blind, placebo-controlled clinical trial, recruited schizophrenia patients who had been maintained on clozapine treatment for at least 18 weeks and had low levels of vitamin D (< 75 nmol/l) and total PANSS scores > 70 (to ascertain the presence of residual symptoms). Patients were randomly allocated to either weekly oral drops of vitamin D (14,000 IU) or placebo and subsequently assessed at two-week intervals for psychosis severity, mood, cognition and metabolic profile.ResultsTwenty four patients were randomly assigned to vitamin D (aged 39.4 ± 9.6 years, 75% males) and the other 23 patients to the placebo arm (aged 42.5 ± 11.2 years, 60.9% males). After eight weeks, the vitamin D group exhibited a significant increase in vitamin D levels (31.4 vs − 0.4 nmol/l, p < 0.0001). There was no significant effect of vitamin D on psychotic, depressive or metabolic parameters. However, in the vitamin D group, there was a trend towards improved cognition (effect size = 0.17, significance lost following Bonferroni correction).ConclusionsVitamin D supplementation was associated with a trend towards improved cognition, but did not affect psychosis, mood or metabolic status. It is possible that the robust decrease in the PANSS scores in both groups may have obscured an effect of vitamin D supplementation.

Simultaneous determination of VD2, VD3, 25(OH) D2, and 25(OH) D3 in human plasma using electrospray LC–MS/MS as well as its application to evaluate VD plasma levels in depressive, schizophrenic patients and healthy individuals

“…An RCT study ( n = 113, 2,640 IU vitamin D3/day for 28 days) found that vitamin D supplementation had no effect on self‐rated depression in adolescent in‐ or daycare patients (Libuda et al, 2020). Another randomized, double‐blind, placebo‐controlled clinical trial ( n = 47, 14,000 IU/week for 8 weeks) found no significant effect of vitamin D supplementation on psychotic, depressive or metabolic parameters in chronic schizophrenia patients treated with clozapine (Krivoy et al, 2017). There are some large‐scale, long‐term RCTs aiming to examine the effects of vitamin D supplementation on mental disorder patients in progress, such as the Vitamin D and OmegA‐3 Trial–Depression Endpoint Prevention (VITAL0DEP) study ( n = 25,874, 2,000 IU/day for a mean period of 5 years) (Okereke et al, 2018).…”

Regulation of Reactive Oxygen Species-Mediated Damage in the Pathogenesis of Schizophrenia

“…Schizophrenia patients are often deficient in vitamin D, which is known to function in neurodevelopment and neuroprotection [ 177 , 178 , 179 , 180 , 181 , 182 ]. The neuroprotective effects of vitamin D arise through modulation of neurotrophin production, calcium homeostasis, neuromediator synthesis, and prevention of oxidative damage [ 183 , 184 , 185 ].…”

The Effects of Vitamin D Deficiency on Neurodegenerative Diseases

“…The authors described no significant effects on psychosis, mood, or metabolic status, but a trend to an improved cognitive function accompanied by significant elevated vitamin D levels in the supplemented group. A possible explanation for these findings, given by the authors, could be that a medical score that measures the symptom severity in schizophrenia patients decreased during the study in the placebo as well as in the treated group and could thereby veil the influence of supplemented vitamin D [174]. An actual study reported beneficial effects of supplementation of vitamin D 3 in combination with probiotics in schizophrenia patients [175].…”