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Prediction of response to risperidone treatment with respect to plasma concencentrations of risperidone, catecholamine metabolites, and polymorphism of cytochrome P450 2D6

Kakihara, Shingo; Yoshimura, Reiji; Shinkai, Koji; Matsumoto, Chima; Goto, Makiko; Kaji, Kyoko; Yamada, Yasuhisa; Ueda, Nobuhisa; Ohmori, Osamu; Nakamura, Jun

International Clinical Psychopharmacology: March 2005 - Volume 20 - Issue 2 - p 71-78

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.

Department of Psychiatry, University Hospital of Occupational and Environmental Health, Kitaykushu, Fukuoka, Japan

Correspondence and requests for reprints to Reiji Yoshimura, Department of Psychiatry, University Hospital of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitaykushu, Fukuoka 807-8555, Japan

Fax: +81 93 692 4894; e-mail:

Received 14 October 2004 Accepted 21 December 2004

© 2005 Lippincott Williams & Wilkins, Inc.