title: Prediction of response to risperidone treatment with respect to plasma concencentrations of risperidone, catecholamine metabolites, and polymorphism of cytochrome P450 2D6.
abstract: In the present study, we examined the relationships between plasma concentrations of risperidone and clinical responses, extrapyramidal symptoms, plasma levels of cotinine and caffeine, or cytochrome (cyp)2D6 genotypes. In addition, we also investigated the relationships between plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) or homovanillic (HVA) acid and clinical responses to risperidone. One hundred and 36 patients (male/female: 58/78, age 37+/-13 years) who met DSM-IV criteria for schizophrenia, schizoaffective disorder, delusional disorder and brief psychotic disorder, and who were being treated with risperidone alone, were evaluated regarding their clinical improvement and extrapyramidal symptoms using the Positive and Negative Syndrome Scale (PANSS) and Simpson and Angus (SAS), respectively, and plasma levels of cotinine, caffeine, MHPG and HVA were analysed by high-performance liquid chromatography. The cyp2D6*5 and *10 alleles were identified using the polymerase chain reaction. There was a positive correlation between plasma levels of risperidone plus 9-hydroxyrisperidone (active moiety) and SAS scores, but not the PANSS. Pretreatment HVA levels in responders were higher than those in nonresponders. In addition, there was a negative correlation between changes in HVA levels and improvement in PANSS scores. There was no association between plasma levels of risperidone and plasma levels of cotinine or caffeine. Furthermore, there were no differences in the risperidone/9-hydroxyrisperidone ratio, clinical improvements and extrapyramidal symptoms among cyp2D6 genotypes. These results indicate that pretreatment HVA levels and plasma concentrations of active moiety might play a part in predicting the clinical response and occurrence of extrapyramidal symptoms, respectively, when treating patients with risperidone.
authors.affiliation: Department of Psychiatry, University Hospital of Occupational and Environmental Health, Kitaykushu, Fukuoka, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kakihara
authors.forename: Reiji
authors.initials: R
authors.lastname: Yoshimura
authors.forename: Koji
authors.initials: K
authors.lastname: Shinkai
authors.forename: Chima
authors.initials: C
authors.lastname: Matsumoto
authors.forename: Makiko
authors.initials: M
authors.lastname: Goto
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kaji
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Yamada
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Ueda
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohmori
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000097:blood; D002110:Caffeine / Q000494:pharmacology; D002395:Catecholamines / Q000097:blood*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003367:Cotinine / Q000097:blood; D003463:Cues; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D007555:Isoxazoles / Q000097:blood; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D011743:Pyrimidines / Q000097:blood; D018967:Risperidone / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D012907:Smoking / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D002395:Catecholamines; D000697:Central Nervous System Stimulants; D007555:Isoxazoles; D011743:Pyrimidines; D002110:Caffeine; D008734:Methoxyhydroxyphenylglycol; D019389:Cytochrome P-450 CYP2D6; D003367:Cotinine; D018967:Risperidone; D000068882:Paliperidone Palmitate; D006719:Homovanillic Acid