The influence of the CYP2D6 polymorphism on psychopathological and extrapyramidal symptoms in the patients on long-term antipsychotic treatment
- 9 January 2006
- journal article
- research article
- Published by SAGE Publications in Journal of Psychopharmacology
- Vol. 20 (6), 829-833
- https://doi.org/10.1177/0269881106062894
Abstract
Poor response to antipsychotics treatment and extrapyramidal side effects (EPS) are the most challenging problems in the treatment of schizophrenia. Several studies were investigating the impact of polymorphic cytochrome P450 2D6 gene ( CYP2D6) on EPS but the results were conflicting. There are practically no clinical studies of long-term treatment of schizophrenia and CYP2D6 polymorphism. Our aim was to evaluate the influence of CYP2D6 genotype on psychopathological symptoms and the occurrence of EPS in Slovenian outpatients with schizophrenia or schizoaffective disorder in stable remission, receiving long-term maintenance antipsychotic treatment. In total 131 outpatients meeting the DSM IV criteria for schizophrenia or schizoaffective disorder and receiving maintenance therapy with haloperidol, fluphenazine, zuclopethixole or risperidone were genotyped for 14 polymorphic CYP2D6alleles. Psychopathological symptoms were assessed with the Positive and Negative Symptom Scale for Schizophrenia (PANSS). EPS were assessed with the Simpson Angus Scale (SAS), the Barnes Akathisia Scale and the Abnormal Involuntary Movement Scale (AIMS). Six patients (4.6%) were genotyped as poor metabolizers (PMs). PMs scored significantly higher on the negative subscale for PANSS. There were no statistically significant differences between the group of PMs and the group of patients with at least one functional CYP2D6 allele in view of patient's characteristics or any of the items of the AIMS, the SAS or the Barnes Akathisia Scale. CYP2D6 genotype may not be the major factor that determines the susceptibility to antipsychotic-induced EPS in Slovenian patients in stable remission and on maintenance therapy with antipsychotics that are mainly CYP2D6 substrates. However, CYP2D6 genotype might be a factor contributing to the persistent negative symptoms of schizophrenia.This publication has 21 references indexed in Scilit:
- Pharmacogenetics of Psychotropic Drug ResponseAmerican Journal of Psychiatry, 2004
- Cytochrome P450 II D6 gene polymorphisms and the neuroleptic-induced extrapyramidal symptoms in Japanese schizophrenic patientsPsychiatric Genetics, 2003
- Decreased capacity for debrisoquine metabolism among black TanzaniansPharmacogenetics, 1999
- Antipsychotic drug-induced movement disorders in schizophrenics in relation to CYP2D6 genotypeThe British Journal of Psychiatry, 1997
- Human CYP2D6 gene polymorphism in Slovene cancer patients and healthy controlsCarcinogenesis: Integrative Cancer Research, 1995
- Polymorphic Drug Metabolism in Schizophrenic Patients With Tardive DyskinesiaJournal of Clinical Psychopharmacology, 1995
- No association between schizophrenia and polymorphisms within the genes for debrisoquine 4-hydroxylase (CYP2D6) and the dopamine transporter (DAT)American Journal of Medical Genetics, 1995
- An association study of debrisoquine hydroxylase (CYP2D6) polymorphisms in schizophreniaPsychiatric Genetics, 1994
- Debrisoquine 4-hydroxylase (CYP2D) locus and possible susceptibility to schizophreniaThe Lancet, 1992
- Genotyping of poor metabolisers of debrisoquine by allele-specific PCR amplificationThe Lancet, 1990