The influence of the CYP2D6 polymorphism on psychopathological and extrapyramidal symptoms in the patients on long-term antipsychotic treatment.
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 CYP2D6 alleles. 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.
Department of Psychiatry, Teaching Hospital Maribor, Maribor, Slovenia.
Blanka Kores
BK
Plesnicar
Bojan
B
Zalar
Katja
K
Breskvar
Vita
V
Dolzan
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004409:Dyskinesia, Drug-Induced / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005838:Genotype; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D011110:Polymorphism, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D011595:Psychomotor Agitation / Q000523:psychology; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6