Abstract
At least 170 approved drugs are linked to QT prolongation, which can lead to serious adverse drug reactions (ADRs), such as Torsade de Pointes (TdP). The aim of this study was to analyze the prevalence and type of pharmacodynamic drug–drug interactions (DDIs) between QT-prolonging drugs in psychiatry. The present retrospective analysis used data from a large pharmacovigilance study, conducted in 10 psychiatric hospitals in Germany. Patients medication lists were screened for QT-prolonging drugs, classified according to the Arizona Center for Education and Research on Therapeutics (AZCERT). In total, 27,396 patient cases (46% female) with a mean (± standard deviation) age of 47 ± 18 years were included in the study. Altogether, 83% of the cases received at least one and up to eight QT-prolonging drugs at the same time. Combination of drugs with a known or possible risk for TdP (according to the AZCERT) was detected in 13,670 cases (50%). Most frequently prescribed psychotropic high-risk drugs (n = 48,995) were the antipsychotics pipamperone (n = 6202), quetiapine (n = 5718), prothipendyl (n = 4298), and risperidone (n = 4265). The replacement of high-risk drugs such as tricyclic antidepressants, levomepromazine, melperone, and promethazine with more tolerable drugs could avoid 11% of QT-prolonging drugs and increase the tolerability of psychopharmacological treatment. More than 80% of psychiatric patients receive at least one QT-prolonging drug during their hospital stay, and almost 50% of these drugs are combined in clinical practice. For the prevention of cardiac ADRs, the physician should evaluate the risk for QT prolongation for each drug and patient-specific risk factors before prescribing these drugs or drug combinations.
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Data transparency was given and controlled by external government in Hesse, Germany.
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Acknowledgements
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, analysis, pharmacological interpretation, and wrote the final manuscript. MH, SCR, ST, 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., Hahn, M., Hiemke, C. et al. Pharmacodynamic Drug–Drug interactions of QT-prolonging drugs in hospitalized psychiatric patients. J Neural Transm 128, 243–252 (2021). https://doi.org/10.1007/s00702-020-02291-y
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DOI: https://doi.org/10.1007/s00702-020-02291-y