Potential for drug interactions involving cytochromes P450 2D6 and 3A4 on general adult psychiatric and functional elderly psychiatric wards

Authors

  • S. J. C. Davies,

    1. Academic Unit of Molecular and Clinical Pharmacology, University of Sheffield, Royal Hallamshire Hospital, Sheffield S10 2JF and
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    • *

      Present address: Psychopharmacology Unit, Dorothy Hodgkin Building, University of Bristol, Whitson Street, Bristol B1 3NY, U.K.

  • S. Eayrs,

    1. Academic Unit of Molecular and Clinical Pharmacology, University of Sheffield, Royal Hallamshire Hospital, Sheffield S10 2JF and
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  • P. Pratt,

    1. Sheffield Care Trust, Michael Carlisle Centre, Sheffield S11 9BF, U.K.
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  • M. S. Lennard

    Corresponding author
    1. Academic Unit of Molecular and Clinical Pharmacology, University of Sheffield, Royal Hallamshire Hospital, Sheffield S10 2JF and
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Dr M. S. Lennard, Academic Unit of Molecular Pharmacology, University of Sheffield, L Floor Royal Hallamshire Hospital, Sheffield S10 2JF, U.K. Tel: + 44 114 271 2578 Fax: + 44 114 272 0275 E-mail: m.s.lennard@sheffield.ac.uk

Abstract

Aims

To assess the potential for interactions involving cytochromes P450 2D6 (CYP2D6) and 3A4 (CYP3A4) between drugs prescribed in a city in-patient psychiatric service.

Methods

Prescription information was obtained from all 236 patients in general adult wards and all 87 patients in functional elderly wards under a city psychiatric service. The frequencies with which combinations of drugs expected to interact via CYP2D6 or CYP3A4 were documented and compared between these two settings.

Results

All 2089 drug prescriptions, of which 1237 (59%) were administered, were analyzed. One hundred and seventy-two patients (73%) on adult wards and 59 (68%) on functional elderly wards were prescribed at least one drug metabolized by and/or inhibiting CYP2D6, the difference being nonsignificant (95% confidence interval on the difference −6.3%, 16.4%). Anticipated interactions from 62/82 CYP2D6-related combinations prescribed on adult wards (27/100 patients) and 19/30 prescribed to elderly patients (22/100 patients) were judged to be clinically important or potentially clinically important. The proportion of patients on functional elderly wards prescribed at least one drug interacting with CYP3A4 (87%) was significantly greater than that for patients on adult wards (57%, P < 0.001). The frequency of interactions involving CYP3A4 was significantly greater on functional elderly than adult wards (43/100 vs 22/100 patients, P < 0.025, 95% confidence interval on the difference 4, 38/100).

Conclusions

Our findings confirm extensive polypharmacy on general adult psychiatric and functional elderly psychiatric wards. A substantial proportion of patients were receiving combinations of drugs that interact with CYP2D6 and/or CYP3A4, many of which are known to produce clinically important interactions. Doctors practising in old age psychiatry should be aware that patients on functional elderly wards are at increased risk of clinically important CYP3A4 interactions. Psychiatrists should consider the pharmacokinetic implications of drugs prescribed for use ‘as needed’, because of the potential for unpredictable interactions.

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