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.