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.
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Significant positive associations have been made between plasma concentration and adverse events of antipsychotics.
“Significant positive associations have been made between plasma concentration and adverse events of APs56; therefore, long-acting injectables warrant further investigation to determine if they may curb autonomic effects of APs and potentially limit the occurrence of adverse side effects of the medications.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [56]
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Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health
Stogios, N., Gdanski, A., Gerretsen, P., Chintoh, A. F., Graff-Guerrero, A., Rajji, T. K., Remington, G., Hahn, M. K., & Agarwal, S. M. (2021) · npj Schizophrenia · doi:10.1038/s41537-021-00151-6 · Cited by 98 · see citing works
Suda, A., Hattori, S., Kishida, I., Miyauchi, M., Shiraishi, Y., Fujibayashi, M., Tsujita, N., Ishii, C., Ishii, N., Moritani, T., et al. (2018) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s173617 · Cited by 5 · see citing works
- Authors
- Kakihara, S., Yoshimura, R., Shinkai, K., Matsumoto, C., Goto, M., Kaji, K., Yamada, Y., Ueda, N., Ohmori, O., & Nakamura, J.
- Affiliations
- University of Occupational and Environmental Health Japan (JP)
- Corresponding author
- Yoshimura, Reiji
- Venue
- International Clinical Psychopharmacology
- Published
- 2005-03
- Volume
- 20
- Issue
- 2
- Pages
- 71-78
- ISSN
- 0268-1315 (ISSN-L)
- OpenAlex
- W2043985392
- Cited by
- 95
- References
- 28
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 2 · 2021: 6 · 2019: 3 · 2018: 6 · 2017: 3 · 2016: 8 · 2015: 1 · 2014: 2 · 2013: 9 · 2012: 6
- FWCI
- 3.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Clinical Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- risperidone, treatment response prediction, extrapyramidal symptoms, homovanillic acid, MHPG, catecholamine metabolites, paliperidone, schizophrenia, antipsychotic pharmacokinetics, CYP2D6*5, CYP2D6*10, plasma cotinine
- MeSH terms
- Paliperidone Palmitate, Adolescent, Adult, Aged, Central Nervous System Stimulants, Basal Ganglia Diseases, Caffeine, Catecholamines, Cotinine, Cues, Female, Homovanillic Acid, Humans, Isoxazoles, Male, Methoxyhydroxyphenylglycol, Middle Aged, Polymorphism, Genetic, Psychiatric Status Rating Scales, Pyrimidines, Schizophrenia, Smoking, Antipsychotic Agents, Risperidone, Cytochrome P-450 CYP2D6
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