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

• Published in: EBioMedicine Vol. 26; no. C; pp. 138 - 145
• Main Authors: Krivoy, Amir, Onn, Roy, Vilner, Yael, Hochman, Eldar, Weizman, Shira, Paz, Amir, Hess, Shmuel, Sagy, Roi, Kimhi-Nesher, Shiri, Kalter, Ehud, Friedman, Tal, Friedman, Zvi, Bormant, Gil, Trommer, Sharon, Valevski, Avi, Weizman, Abraham
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2017; Elsevier
• Subjects: Adult; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Clozapine; Clozapine - administration & dosage; Clozapine - adverse effects; Cognition; Cognition - drug effects; Cognition - physiology; Dietary Supplements; Double-Blind Method; Female; Humans; Male; Metabolic syndrome; Metabolic Syndrome - blood; Metabolic Syndrome - diet therapy; Metabolic Syndrome - drug therapy; Metabolic Syndrome - pathology; Middle Aged; Mood; Psychotic Disorders - blood; Psychotic Disorders - diet therapy; Psychotic Disorders - drug therapy; Psychotic Disorders - pathology; Research Paper; Schizophrenia; Schizophrenia - blood; Schizophrenia - diet therapy; Schizophrenia - drug therapy; Schizophrenia - pathology; Vitamin D; Vitamin D - administration & dosage; Vitamin D - blood; Schizophrenia; Cognition; Mood; Clozapine; Vitamin D; Metabolic syndrome
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2017.11.027

While 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.
This eight-week, randomized, double-blind, placebo-controlled clinical trial, recruited schizophrenia patients who had been maintained on clozapine treatment for at least 18weeks and had low levels of vitamin D (<75nmol/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 (14,000IU) or placebo and subsequently assessed at two-week intervals for psychosis severity, mood, cognition and metabolic profile.
Twenty four patients were randomly assigned to vitamin D (aged 39.4±9.6years, 75% males) and the other 23 patients to the placebo arm (aged 42.5±11.2years, 60.9% males). After eight weeks, the vitamin D group exhibited a significant increase in vitamin D levels (31.4 vs −0.4nmol/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).
Vitamin 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.
•This is the first study to explore the effects of vitamin D supplementation in chronic schizophrenia patients on clozapine•In this randomized double-blind study, patients received supplement vitamin D (14,000IU weekly) or placebo for eight weeks•There was no difference between vitamin D and placebo with regards to severity of psychopathology or metabolic status•There was a trend towards improved cognition following the effect of vitamin D specifically in attention and delayed recall
About third of schizophrenia patients do not respond to common antipsychotics and require a clozapine trial. Insufficient levels of serum Vitamin D, the sunshine hormone, were found to be very prevalent among schizophrenia patients. The vitamin has a potent active metabolite with specific receptors in the brain. We investigated the psychiatric, metabolic and cognitive effects of vitamin D supplementation in comparison to placebo in clozapine-treated chronic schizophrenia patients with residual psychotic symptoms. Vitamin D addition was not superior to placebo in reducing psychiatric symptoms or improving the metabolic parameters. However, vitamin D administration was associated with a trend towards improvement in cognitive performance.