Effect of CYP2D6 polymorphisms on plasma concentration and therapeutic effect of risperidone
Abstract Background This study aimed to investigate the influence of CYP2D6 polymorphisms on risperidone plasma concentrations in patients with schizophrenia. Based on pharmacogenomics, we examined whether plasma concentration of risperidone is associated with clinical response and adverse side-effe...
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | BMC Psychiatry |
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| Online Access: | https://doi.org/10.1186/s12888-020-03034-9 |
| _version_ | 1818456048584884224 |
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| author | Jinjun Lu Ye Yang Jian Lu Zuqing Wang Yiping He Yeliang Yan Kai Fu Wenjuan Jiang Yunqing Xu Renrong Wu Wenqing Liu Jingping Zhao |
| author_facet | Jinjun Lu Ye Yang Jian Lu Zuqing Wang Yiping He Yeliang Yan Kai Fu Wenjuan Jiang Yunqing Xu Renrong Wu Wenqing Liu Jingping Zhao |
| author_sort | Jinjun Lu |
| collection | DOAJ |
| description | Abstract Background This study aimed to investigate the influence of CYP2D6 polymorphisms on risperidone plasma concentrations in patients with schizophrenia. Based on pharmacogenomics, we examined whether plasma concentration of risperidone is associated with clinical response and adverse side-effects. Methods We recruited patients with chronic schizophrenia who were then treated with risperidone. The CYP2D6 genotypes were determined using targeted sequencing. All high-frequency mutation sites of the nine exons of the gene were assayed in the present study. Plasma concentrations of risperidone and 9-hydroxyrisperidone (9-OH-RIS) were measured using high-performance liquid chromatography (HPLC). Psychiatric symptoms were monitored using The Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI). Adverse effects were evaluated using the Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS). Follow-up visits were scheduled at weeks 2,4, and 8 after treatment initiation. Results Among the 76 patients, 100 C > T (rs1065852), 1038 C > T (rs1081003), 1662 G > C (rs1058164), 2851 C > T (rs16947), and 4181G > C (rs1135840) variants were detected. The most common allele was CYP2D6*10 (81.6%), whereas CYP2D6*2 (9.2%) and CYP2D6*5 (17.1%) were relatively rare. Plasma levels of risperidone and the risperidone/9-OH risperidone ratio (R/9-OH) were significantly increased in individuals with CYP2D6*10 (P < 0.05). The change in PANSS score, weight, high-density lipoprotein (HDL) level, prolactin (PRL) level, and ESRS were significantly different from baseline, between the different genotypes (P < 0.01). Moreover, individuals with CYP2D6*10 homozygous (TT) mutations were associated with higher risperidone concentration and R/9-OH ratio than those with heterozygous mutations (CT) (P < 0.01). A change from baseline in BPRS scores was observed only during week 8 and was different between heterozygous and homozygous mutations. As for the C2851T polymorphism, the incidence of adverse metabolic effects was significantly different between the C/C and C/T genotypes (P < 0.01). Regarding the G4181C polymorphisms, the changes from baseline in GLU and TG, were different between the C/C and C/G genotypes (P < 0.01). Conclusions The genotype of CYP2D6 significantly influences the plasma concentration of risperidone and may subsequently influence the adverse side-effects following risperidone treatment, while also exerting a slight influence on clinical outcomes. |
| first_indexed | 2024-12-14T22:20:29Z |
| format | Article |
| id | doaj.art-f1592137a84f498bbaf9483b8a38533a |
| institution | Directory Open Access Journal |
| issn | 1471-244X |
| language | English |
| last_indexed | 2024-12-14T22:20:29Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
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| series | BMC Psychiatry |
| spelling | doaj.art-f1592137a84f498bbaf9483b8a38533a2022-12-21T22:45:31ZengBMCBMC Psychiatry1471-244X2021-02-0121111210.1186/s12888-020-03034-9Effect of CYP2D6 polymorphisms on plasma concentration and therapeutic effect of risperidoneJinjun Lu0Ye Yang1Jian Lu2Zuqing Wang3Yiping He4Yeliang Yan5Kai Fu6Wenjuan Jiang7Yunqing Xu8Renrong Wu9Wenqing Liu10Jingping Zhao11The Third People’s Hospital of Jiangyin CityNational Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South UniversityThe Third People’s Hospital of Jiangyin CityThe Third People’s Hospital of Jiangyin CityThe Third People’s Hospital of Jiangyin CityThe Third People’s Hospital of Jiangyin CityThe Third People’s Hospital of Jiangyin CityThe Third People’s Hospital of Jiangyin CityThe Third People’s Hospital of Jiangyin CityNational Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South UniversityThe Third People’s Hospital of Jiangyin CityNational Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South UniversityAbstract Background This study aimed to investigate the influence of CYP2D6 polymorphisms on risperidone plasma concentrations in patients with schizophrenia. Based on pharmacogenomics, we examined whether plasma concentration of risperidone is associated with clinical response and adverse side-effects. Methods We recruited patients with chronic schizophrenia who were then treated with risperidone. The CYP2D6 genotypes were determined using targeted sequencing. All high-frequency mutation sites of the nine exons of the gene were assayed in the present study. Plasma concentrations of risperidone and 9-hydroxyrisperidone (9-OH-RIS) were measured using high-performance liquid chromatography (HPLC). Psychiatric symptoms were monitored using The Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI). Adverse effects were evaluated using the Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS). Follow-up visits were scheduled at weeks 2,4, and 8 after treatment initiation. Results Among the 76 patients, 100 C > T (rs1065852), 1038 C > T (rs1081003), 1662 G > C (rs1058164), 2851 C > T (rs16947), and 4181G > C (rs1135840) variants were detected. The most common allele was CYP2D6*10 (81.6%), whereas CYP2D6*2 (9.2%) and CYP2D6*5 (17.1%) were relatively rare. Plasma levels of risperidone and the risperidone/9-OH risperidone ratio (R/9-OH) were significantly increased in individuals with CYP2D6*10 (P < 0.05). The change in PANSS score, weight, high-density lipoprotein (HDL) level, prolactin (PRL) level, and ESRS were significantly different from baseline, between the different genotypes (P < 0.01). Moreover, individuals with CYP2D6*10 homozygous (TT) mutations were associated with higher risperidone concentration and R/9-OH ratio than those with heterozygous mutations (CT) (P < 0.01). A change from baseline in BPRS scores was observed only during week 8 and was different between heterozygous and homozygous mutations. As for the C2851T polymorphism, the incidence of adverse metabolic effects was significantly different between the C/C and C/T genotypes (P < 0.01). Regarding the G4181C polymorphisms, the changes from baseline in GLU and TG, were different between the C/C and C/G genotypes (P < 0.01). Conclusions The genotype of CYP2D6 significantly influences the plasma concentration of risperidone and may subsequently influence the adverse side-effects following risperidone treatment, while also exerting a slight influence on clinical outcomes.https://doi.org/10.1186/s12888-020-03034-9CYP2D6PolymorphismsRisperidonePlasma concentrationTherapeutic effect |
| spellingShingle | Jinjun Lu Ye Yang Jian Lu Zuqing Wang Yiping He Yeliang Yan Kai Fu Wenjuan Jiang Yunqing Xu Renrong Wu Wenqing Liu Jingping Zhao Effect of CYP2D6 polymorphisms on plasma concentration and therapeutic effect of risperidone BMC Psychiatry CYP2D6 Polymorphisms Risperidone Plasma concentration Therapeutic effect |
| title | Effect of CYP2D6 polymorphisms on plasma concentration and therapeutic effect of risperidone |
| title_full | Effect of CYP2D6 polymorphisms on plasma concentration and therapeutic effect of risperidone |
| title_fullStr | Effect of CYP2D6 polymorphisms on plasma concentration and therapeutic effect of risperidone |
| title_full_unstemmed | Effect of CYP2D6 polymorphisms on plasma concentration and therapeutic effect of risperidone |
| title_short | Effect of CYP2D6 polymorphisms on plasma concentration and therapeutic effect of risperidone |
| title_sort | effect of cyp2d6 polymorphisms on plasma concentration and therapeutic effect of risperidone |
| topic | CYP2D6 Polymorphisms Risperidone Plasma concentration Therapeutic effect |
| url | https://doi.org/10.1186/s12888-020-03034-9 |
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