Vitamin D impact in affecting clozapine plasma exposure: A potential contribution of seasonality

Schizophrenia affects approximately 24 million people worldwide and clozapine is the most effective antipsychotic drug. Nevertheless, its use in therapy is limited due to adverse effects.Therapeutic drug monitoring is a clinical tool useful to reduce the clozapine toxicity. In the literature, papers showed how psychiatric disorders could be associated with low vitamin D levels, but a few studies focusing on its role in affecting clozapine exposure are available. A TDM repository was analyzed: clozapine and vitamin D levels measured with liquid chromatography were considered. 1261 samples obtained from 228 individuals were evaluated: 624 patients (49.5%) showed clozapine plasma levels in therapeutic range (350-600 ng/mL). Clozapine toxic plasma levels (>1000 ng/mL) were more present in winter (p = 0.025), compared to other seasons. Concerning vitamin D, a sub-analysis of 859 samples was performed: 326 (37.81%) were deficient ( ng/mL), 490 (57.12%) had insufficient concentrations (10-30 ng/mL), while 43 (5.02%) had sufficient (>30 ng/mL) levels. A correlation between vitamin D and clozapine plasma levels (p = 0.007, Pearson coefficient=0.093) was observed. The role of seasonal variation in clozapine plasma exposure in psychiatric patients treated with clozapine was suggested. Further studies in larger cohorts are needed in order to clarify these aspects.