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  • 1
    In: British Journal of Clinical Pharmacology, Wiley, Vol. 88, No. 7 ( 2022-07), p. 3193-3200
    Abstract: Patients with schizophrenia frequently show insufficient vitamin D levels, which are associated with somatic comorbidity and may contribute to psychopathology. For many reasons, vitamin D supplementation may be indicated for this patient cohort. However, there is growing evidence for a vitamin D‐mediated increase of drug metabolism by induction of cytochrome P450 (CYP) 3A4. Hence, this study aimed to assess vitamin D's impact on both antipsychotic drug concentrations and psychopathology in a non‐interventional manner. Methods Totals of 107 serum concentrations of different antipsychotic drugs (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine and risperidone), 80 serum concentrations of vitamin D and psychopathological assessments were obtained from 80 patients with schizophrenia. The impact of Vitamin D on antipsychotic drug concentrations and symptomatology was assessed using a generalized linear model, path and correlation analyses. Results We observed a negative relationship between vitamin D and dose‐adjusted antipsychotic drug concentrations, which was particularly pronounced for drugs which are predominantly metabolized via CYP3A4 (i.e., aripiprazole and quetiapine). A path analysis suggested a relieving effect of vitamin D on symptomatology which was, however, counteracted by its negative impact on antipsychotic drug levels. Finally, patients with vitamin D levels above the median exhibited a significantly higher proportion of therapeutically insufficient dose‐normalized drug concentrations of aripiprazole and quetiapine. Conclusion Despite vitamin D's potential benefits on physical and mental health, clinicians should be aware of its negative impact on blood concentrations of antipsychotics metabolized by CYP3A4 in patients with schizophrenia. Therefore, when considering its supplementation, therapeutic drug monitoring should be applied to guide dose adjustment.
    Type of Medium: Online Resource
    ISSN: 0306-5251 , 1365-2125
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1498142-7
    SSG: 15,3
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  • 2
    In: Biomedicines, MDPI AG, Vol. 10, No. 5 ( 2022-05-09), p. 1096-
    Abstract: Vitamin D deficiency is a frequent finding in schizophrenia and may contribute to neurocognitive dysfunction, a core element of the disease. However, there is limited knowledge about the neuropsychological profile of vitamin D deficiency-related cognitive deficits and their underlying molecular mechanisms. As an inductor of cytochrome P450 3A4, a lack of vitamin D might aggravate cognitive deficits by increased exposure to anticholinergic antipsychotics. This cross-sectional study aims to assess the relationship between 25-OH-vitamin D-serum concentrations, anticholinergic drug exposure and neurocognitive functioning (Brief Assessment of Cognition in Schizophrenia, BACS, and Trail Making Test, TMT) in 141 patients with schizophrenia. The anticholinergic drug exposure was estimated by adjusting the concentration of each drug for its individual muscarinic receptor affinity. Using regression analysis, we observed a positive relationship between vitamin D levels and processing speed (TMT-A and BACS Symbol Coding) as well as executive functioning (TMT-B and BACS Tower of London). Moreover, a negative impact of vitamin D on anticholinergic drug exposure emerged, but the latter did not significantly affect cognition. When other cognitive items were included as regressors, the impact of vitamin D remained only significant for the TMT-A. Among the different cognitive impairments in schizophrenia, vitamin D deficiency may most directly affect processing speed, which in turn may aggravate deficits in executive functioning. This finding is not explained by a cytochrome P450-mediated increased exposure to anticholinergic antipsychotics.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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