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The negative impact of vitamin D on antipsychotic drug exposure may counteract its potential benefits in schizophrenia

Aims 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...

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Main Authors: Gaebler, Arnim (Author) , Finner-Prével, Michelle (Author) , Lammertz, Sarah (Author) , Schaffrath, Sabrina (Author) , Eisner, Patrick (Author) , Stöhr, Felix (Author) , Röcher, Erik (Author) , Winkler, Lina (Author) , Kaleta, Peter (Author) , Lenzen, Laura (Author) , Augustin, Marc (Author) , Hovancakova, Jana (Author) , Schwemmer, Lara (Author) , Stormanns, Eva (Author) , Keskin, Fatih (Author) , Hendricks, Frederik (Author) , Paulzen, Michael (Author) , Gründer, Gerhard (Author) , Schneider, Frank (Author) , Mathiak, Klaus (Author)
Format: Article (Journal)
Language:English
Published: 09 January 2022
In: British journal of clinical pharmacology
Year: 2022, Volume: 88, Issue: 7, Pages: 3193-3200
ISSN:1365-2125
DOI:10.1111/bcp.15223
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1111/bcp.15223
Verlag, kostenfrei, Volltext: http://onlinelibrary.wiley.com/doi/abs/10.1111/bcp.15223
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Author Notes:Arnim Johannes Gaebler, Michelle Finner-Prével, Sarah Lammertz, Sabrina Schaffrath, Patrick Eisner, Felix Stöhr, Erik Röcher, Lina Winkler, Peter Kaleta, Laura Lenzen, Marc Augustin, Jana Hovancakova, Lara Schwemmer, Eva Stormanns, Fatih Keskin, Frederik Hendricks, Michael Paulzen, Gerhard Gründer, Frank Schneider, Apic Consortium, Klaus Mathiak
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Summary:Aims 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.
Item Description:Gesehen am 21.11.2023
Physical Description:Online Resource
ISSN:1365-2125
DOI:10.1111/bcp.15223

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