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.
Article: Pharmacogenetics of antipsychotics.[Show abstract] [Hide abstract]
ABSTRACT: During the past decades, increasing efforts have been invested in studies to unravel the influence of genetic factors on antipsychotic (AP) dosage, treatment response, and occurrence of adverse effects. These studies aimed to improve clinical care by predicting outcome of treatment with APs and thus allowing for individualized treatment strategies. We highlight most important findings obtained through both candidate gene and genome-wide association studies, including pharmacokinetic and pharmacodynamic factors.Canadian journal of psychiatry. Revue canadienne de psychiatrie 02/2014; 59(2):76-88. · 2.48 Impact Factor
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ABSTRACT: This study sought to examine whether switching polypharmacy therapy to monotherapy would improve the cognitive function and social function of patients with schizophrenia. Thirty-nine patients with schizophrenia who were receiving therapy with two antipsychotics were randomly divided into a switch to monotherapy group (switching group) and a polypharmacy continued group (continuing group). For the patients allocated to the switching group, the dose level of one of the two antipsychotic drugs was gradually reduced to zero. Psychotic symptoms, cognitive function and social function scale scores were assessed immediately before and 24 weeks after switching, and the time courses of these scores were compared between the two groups. Compared with the continuing group, the switching group demonstrated significantly greater improvement in attention after switching (p = 0.02). Furthermore, the improvement in daily living (p = 0.038) and work skills (p = 0.04) was significantly greater in the switching group. In an analysis of the correlation among sub-items with respect to the degrees of improvement, a significant correlation was noted between improvement in executive function and improvement in daily living (r = -0.64, p = 0.005) and between improvement in work skills and improvement in attention (r = -0.51, p = 0.038). In patients with schizophrenia receiving polypharmacy, switching to monotherapy resulted in improvements in attention. Furthermore, improvements in executive function led to improvements in daily living, and improvements in attention led to improvements in work skills. Thus, switching to monotherapy is a useful option.Journal of Psychiatric Research 09/2013; · 4.09 Impact Factor
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ABSTRACT: Abstract Adverse events, response failures and medication non-compliance are common in patients receiving medications for the treatment of mental illnesses. A systematic literature review assessed whether pharmacokinetic (PK) or pharmacodynamic (PD) responses to 26 commonly prescribed antipsychotic and antidepressant medications, including efficacy or side effects, are associated with nucleotide polymorphisms in eight commonly studied genes in psychiatric pharmacotherapy: CYP2D6, CYP2C19, CYP2C9, CYP1A2, CYP3A4, HTR2C, HTR2A, and SLC6A4. Of the 294 publications included in this review, 168 (57%) showed significant associations between gene variants and PK or PD outcomes. Other studies that showed no association often had insufficient control for confounding variables, such as co-medication use, or analysis of medications not substrates of the target gene. The strongest gene-outcome associations were for the PK profiles of CYP2C19 and CYP2D6 (93% and 90%, respectively), for the PD associations between HTR2C and weight gain (57%), and for SLC6A4 and clinical response (54%), with stronger SLC6A4 response associations for specific drug classes (60-83%). The preponderance of evidence supports the validity of analyzing nucleotide polymorphisms in CYP and pharmacodynamic genes to predict the metabolism, safety, or therapeutic efficacy of psychotropic medications commonly used for the treatment of depression, schizophrenia, and bipolar illness.International Review of Psychiatry 10/2013; 25(5):509-33. · 1.80 Impact Factor