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

Randomized, double-blind, placebo-controlled clinical trial in adults with schizophrenia on stable clozapine treatment and low vitamin D levels, including inpatients and outpatients. The active vitamin D arm included 24 participants at Geha Mental Health Center in Petah-Tikva, Israel.

Vitamin D was given as oral drops at 14,000 IU per week (0.35 mg; 35 drops) for 8 weeks, added to ongoing clozapine treatment. The comparator was placebo in a randomized, double-blind design.

Vitamin D supplementation clearly increased 25(OH)D levels, but it did not produce a meaningful clinical benefit for psychotic symptoms or metabolic outcomes. PANSS total change was not different between groups (-8.9 vs -10; between-group p=0.65), and metabolic endpoints such as BMI, glucose, HbA1C, blood pressure, and pulse were also not significantly changed. A small improvement in MoCA was seen (p=0.04), but it did not remain significant after adjustment for multiple comparisons. Endpoint vitamin D deficiency was less common in the vitamin D group (1 [4%]) than in placebo (4 [17%]).

The trial was small and lasted only 8 weeks, limiting power to detect modest clinical effects. The apparent cognitive signal was weak and did not survive multiple-comparison adjustment, and substantial improvement in both groups may have obscured any true treatment effect. Generalizability is limited to clozapine-treated schizophrenia patients with low vitamin D levels.