Does the medication pattern reflect the CYP2D6 genotype in patients with diagnoses within the schizophrenic spectrum?

Gesche Jürgens, Henrik B. Rasmussen, Thomas Werge, Kim Dalhoff, Merete Nordentoft, Stig E. Andersen

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    Abstrakt

    BACKGROUND: Cytochrome P450 2D6 enzyme (CYP2D6) is an important metabolic pathway for many antipsychotics. Its genetic polymorphism causes pharmacokinetic variability that might lead to adverse drug reactions or treatment failure unless countered by appropriate dose adjustments or shift to CYP2D6-independent antipsychotics. PURPOSE: To investigate the clinical impact of CYP2D6 genotype in patients with a diagnosis within the schizophrenic spectrum using medication pattern as proxy for therapeutic and side effect. METHODS: The study was conducted in patients genotyped during an inpatient stay (N = 576). Continuous antipsychotic, adjuvant, and anticholinergic drug regimens were registered retrospectively in a cross-sectional manner before genotyping. Antipsychotics were divided into CYP2D6 dependent and independent, and dose equivalents were calculated as chlorpromazine equivalents (CPZEq). RESULTS: Poor metabolizers and ultrarapid metabolizers were treated with significantly higher median CPZEq doses (625.8; inter quartile range [IQR], 460.4-926.7; and 550; IQR, 199.8-1049) than extensive metabolizers (EMs) and intermediate metabolizers (IMs) (384; IQR, 150-698; and 446; IQR, 150-800) (P = 0.018). Logistic regression showed no association between anticholinergic treatment and CYP2D6 genotype or concomitant treatment with CYP2D6 inhibitors (P = 0.79 and P = 0.46, respectively). CONCLUSIONS: Our results indicate that CYP2D6 genotype has no sufficient clinical impact that poor metabolizers and ultrarapid metabolizers are easily clinically identified with.

    OriginalsprogEngelsk
    Sider (fra-til)100-105
    Antal sider6
    TidsskriftJournal of Clinical Psychopharmacology
    Vol/bind32
    Udgave nummer1
    DOI
    StatusUdgivet - 1 feb. 2012

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