Depot Haloperidol Treatment in Outpatients With Schizophrenia on Monotherapy: Impact of CYP2D6 Polymorphism on Pharmacokinetics and Treatment Outcome
Abstract
Haloperidol and several other antipsychotic drugs are at least partially metabolized by the polymorphic cytochrome P450 2D6 (CYP2D6). The interindividual variation in metabolic capacity of CYP2D6 might be of importance when dosing. In this study, 26 outpatients with schizophrenia and depot haloperidol as monotherapy were genotyped. The authors found 1 patient with no functional alleles, 8 with one functional allele, 16 with two functional alleles, and 1 with three functional alleles. The daily dose of haloperidol ranged from 0.45 to 14.29 mg. Steady state plasma concentrations were measured at peak (range, 1.6-67 nmol/L) and at trough (range, 1.0-49 nmol/L). The Positive and Negative Syndrome scale for Schizophrenia and the Extrapyramidal Symptom Rating Scale were used to evaluate the clinical effect. The authors found a clear correlation between haloperidol plasma concentration and number of active CYP2D6 alleles. No correlation was found between plasma concentration of haloperidol or number of CYP2D6 alleles and treatment outcome or side effects. A model to predict plasma concentration from dose and number of active CYP2D6 alleles was formed from the obtained data by means of multiple linear regression.
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Concomitant administration of haloperidol decanoate with CYP3A4 inducers, such as rifampin and carbamazepine, may require dose increases.
“concomitant administration with CYP3A4 inducers, such as rifampin and carbamazepine, may require haloperidol decanoate dose increases [54, 58]”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [58]
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Correll, C. U., Kim, E., Sliwa, J. K., Hamm, W., Gopal, S., Mathews, M., Venkatasubramanian, R., & Saklad, S. R. (2021) · CNS Drugs · doi:10.1007/s40263-020-00779-5 · Cited by 205 · see citing works
- Authors
- Panagiotidis, G., Arthur, H. W., Lindh, J. D., Dahl, M.-L., & Sjöqvist, F.
- Affiliations
- Karolinska University Hospital (SE)
- Uppsala University Hospital (SE)
- Corresponding author
- Panagiotidis, Georgios
- Lindh, Jonatan D
- Sjöqvist, Folke
- Venue
- Therapeutic Drug Monitoring
- Published
- 2007-08
- Volume
- 29
- Issue
- 4
- Pages
- 417-422
- ISSN
- 0163-4356 (ISSN-L)
- OpenAlex
- W2002894637
- Cited by
- 32
- References
- 26
- Citations by year
- 2026: 1 · 2023: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2014: 2 · 2013: 5 · 2012: 2
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Therapeutic Drug Monitoring (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Karolinska Institutet
- Vetenskapsrådet
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- haloperidol, schizophrenia, CYP2D6 polymorphism, pharmacokinetics, genotype-phenotype correlation, plasma concentration, antipsychotic monotherapy, extrapyramidal symptoms, treatment outcomes, dose prediction model, drug metabolism
- MeSH terms
- Adult, Alleles, Chromatography, High Pressure Liquid, Delayed-Action Preparations, Dose-Response Relationship, Drug, Female, Genotype, Haloperidol, Humans, Injections, Intramuscular, Male, Middle Aged, Outpatients, Polymorphism, Genetic, Schizophrenia, Antipsychotic Agents, Treatment Outcome, Cytochrome P-450 CYP2D6
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