Abstract
Psychiatric patients are high-risk patients for the development of pharmacokinetic drug–drug interactions (DDIs), leading to highly variable (victim) drug serum concentrations. Avoiding and targeting high-risk drug combinations could reduce preventable adverse drug reactions (ADRs). Pharmacokinetic cytochrome P450 (CYP)-mediated DDIs are often predictable and, therefore, preventable. The retrospective, longitudinal analysis used informations from a large pharmacovigilance study (Optimization of pharmacological treatment in hospitalized psychiatric patients study, study number 01VSF16009, 01/2017), conducted in 10 psychiatric hospitals in Germany. Medication data were examined for the co-prescription of clinically relevant CYP inhibitors or inducers and substrates of these enzymes (victim drugs). In total, data from 27,396 patient cases (45.6% female) with a mean (mean ± standard deviation (SD)) age of 47.3 ± 18.3 years were available for analysis. CYP inhibitors or inducers were at least once prescribed in 14.4% (n = 3946) of the cases. The most frequently prescribed CYP inhibitors were melperone (n = 2504, 28.1%) and duloxetine (n = 1324, 14.9%). Overall, 51.0% of the cases taking melperone were combined with a victim drug (n = 1288). Carbamazepine was the most frequently prescribed CYP inducer (n = 733, 88.8%). Combinations with victim drugs were detected for 58% (n = 427) of cases on medication with carbamazepine. Finally, a DDI was detected in 43.6% of the cases in which a CYP inhibitor or inducer was prescribed. The frequency of CYP-mediated DDI is considerably high in the psychiatric setting. Physicians should be aware of the CYP inhibitory and inducing potential of psychotropic and internistic drugs (especially, melperone).
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The authors are very grateful to all 10 participating hospitals for their voluntary collection of data.
Funding
The Federal Joint Committee (G-BA, project executing organization: Deutsches Zentrum für Luft- und Raumfahrt, DLR) is funding healthcare research projects that aim to optimize quality of care for statutory insured persons in Germany. In this regard, the innovative study “Optimization of pharmacological treatment in hospitalized psychiatric patients” (OSA-PSY, study number 01VSF16009, ethical approval reference number FF 116/2017) is sponsored by the DLR.
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GH did literature search, did analysis, pharmacological interpretation and wrote the final manuscript. MH, SCR, ST, TM and CH did analysis and pharmacological interpretation of the manuscript. JW did statistical analysis of patient data. AK gave the idea, made data analysis and interpretation of study results.
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Gudrun Hefner, Martina Hahn, Sibylle C. Roll, Jan Wolff and Ansgar Klimke declare no conflicts of interest/ competing interests. Sermin Toto has been a member of an advisory board for Otsouka, and has received speaker’s honoraria from Janssen Cilag, Lundbeck, Otsouka and Servier. Christoph Hiemke has received speaker’s and consultancy fees from Stada, Lohmann Transdermal Systems and Otsuka during the last two years.
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Ethical approval in November 2017 in Hesse, Germany; reference number FF 116/2017.
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Hefner, G., Wolff, J., Hahn, M. et al. Prevalence and sort of pharmacokinetic drug–drug interactions in hospitalized psychiatric patients. J Neural Transm 127, 1185–1198 (2020). https://doi.org/10.1007/s00702-020-02214-x
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DOI: https://doi.org/10.1007/s00702-020-02214-x