Pharmacogenomic response of low dose haloperidol in critically ill adults with delirium

To characterize the pharmacogenomic response of low-dose haloperidol for delirium treatment in critically ill adults. Single-center, pilot study of a convenience sample of ICU adults with delirium treated with low-dose IV haloperidol. Patients were evaluated for delirium with the ICDSC every 8 h. Se...

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Bibliographic Details
Published in:Journal of critical care 2020-06, Vol.57, p.203-207
Main Authors: Trogrlić, Zoran, van der Jagt, Mathieu, Osse, Robert Jan, Devlin, John W., Nieboer, Daan, Koch, Birgit C.P., van Schaik, Ron H.N., Hunfeld, Nicole G.M.
Format: Article
Language:English
Subjects:
Adult
Adults
Age
Aged
Antipsychotic Agents - pharmacology
Clinical outcomes
Critical Illness
Cytochrome P-450 CYP2D6 - genetics
Cytochrome P-450 CYP3A - genetics
Data collection
Delirium
Delirium - drug therapy
Delirium - genetics
Female
Genotype
Haloperidol
Haloperidol - pharmacology
Humans
Intensive care
Male
Middle Aged
Patients
Pharmacodynamics
Pharmacogenetics
Pharmacokinetics
Pilot Projects
Prospective Studies
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Summary:To characterize the pharmacogenomic response of low-dose haloperidol for delirium treatment in critically ill adults. Single-center, pilot study of a convenience sample of ICU adults with delirium treated with low-dose IV haloperidol. Patients were evaluated for delirium with the ICDSC every 8 h. Serum haloperidol concentrations were collected on ICU days 2–6, CYP2D6 and CYP3A4 genotypes were characterized and patients were categorized as extensive (EM), intermediate (IM) or poor metabolizers (PM). The 22 patients (median age 67 [IQR 48,77] years; median APACHE III 81[IQR 54,181]; CYP2D6 [EM = 12, IM = 7, PM = 3], CYP3A [EM = 18, IM = 4]) received a median [IQR] daily haloperidol dose of 3.0 [2.4, 4.5] mg. After adjusting for age, SOFA, and ICU day, neither an association between CYP2D6 (IM p = .67/PM p = .25) or CYP3A4 (IM p = .44) metabolizer status and serum haloperidol concentrations was found. After adjusting for age, SOFA, and ICU day, neither an association between daily haloperidol dose (p = .77) or ICDSC score (p = .13) and serum haloperidol concentrations was found. No patient experienced QTc interval prolongation (≥500 ms). This pilot study, the first to evaluate the pharmacogenomic response of low-dose haloperidol when used to treat delirium in the ICU, suggests CYP2D6/CYP3A4 metabolizer status does not affect the serum haloperidol concentrations. •No association was observed between serum haloperidol concentration and CYP2D6/3A4.•Low dose haloperidol does not seem to decrease delirium symptoms at the ICU.•Future therapeutic haloperidol studies should consider pharmacogenomics and dose.
ISSN:0883-9441
1557-8615
DOI:10.1016/j.jcrc.2020.03.001