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

Eight-week, parallel-arm, randomized, double-blind, placebo-controlled trial in adults with schizophrenia on clozapine for ≥18 weeks. Inclusion: serum 25(OH) vitamin D <75 nmol/L and PANSS total >70. Inpatients and outpatients. 47 randomized (24 vitamin D; 23 placebo); age range 22–65; majority male.

Vitamin D drops, 14,000 IU per week (0.35 mg), for 8 weeks; taken orally as drops (35 drops per week).

Vitamin D increased serum 25(OH)D from 37.2 to 68.6 nmol/L (p<0.0001); placebo changed from 42.7 to 42.3 nmol/L. No significant between-group differences in PANSS total or subscales, depressive symptoms or metabolic parameters over 8 weeks. MoCA total score improved modestly with vitamin D (0.9 vs -0.6; p=0.04), but significance did not survive Bonferroni correction (threshold ~0.007). Regression suggested vitamin D predicted greater MoCA improvement (p=0.016). Conclusion: Vitamin D did not affect psychosis, mood, or metabolic status; a small cognitive benefit is possible, but longer and/or higher-dose studies are needed to confirm.

- Small sample size; short duration. - Treatment-resistant clozapine-treated population; limited generalizability. - PANSS reductions in both groups may obscure effects. - No ethnicity adjustment; potential confounding. - Dose/duration may be insufficient to affect metabolic parameters; possible dose–response effects not assessed. - Multiple comparisons increase risk of Type I error; some cognitive findings did not remain significant. - Intention-to-treat with last observation carried forward; potential bias from missing data.