Metabolism of risperidone by CYP2D6 and the presence of drug-induced dopamine supersensitivity psychosis in patients with schizophrenia.

Autor: Kanahara N; Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University.; Department of Psychiatry, Chiba University Graduate School of Medicine., Yoshimura K; Department of Psychiatry, Chiba University Graduate School of Medicine.; Health Care Management Center, Chiba University Hospital.; Department of psychiatry, Shoushin-kai Mobara Shinkei-ka Hospital., Nakamura M; Department of Psychiatry, Chiba University Graduate School of Medicine., Oda Y; Department of Psychiatry, Chiba University Graduate School of Medicine., Watanabe M; Department of psychiatry, Shouhaku-kai Fujita Hospital, Chiba, Japan., Iyo M; Department of Psychiatry, Chiba University Graduate School of Medicine.
Jazyk: angličtina
Zdroj: International clinical psychopharmacology [Int Clin Psychopharmacol] 2019 May; Vol. 34 (3), pp. 124-130.
DOI: 10.1097/YIC.0000000000000257
Abstrakt: High-dose antipsychotic(s) can induce dopamine supersensitivity psychosis in schizophrenia patients. The precise relationship between a drug's blood concentration and the occurrence of dopamine supersensitivity psychosis has not been established. We divided 36 patients with schizophrenia who had undergone treatment mainly with risperidone into two groups: one with normal metabolizing activity of CYP2D6 (n = 15), and the other with lower activity of its variant, CYP2D6*10 (n = 21). The patients' blood concentrations of risperidone and 9-OH-risperidone were measured, and we compared the occurrence of dopamine supersensitivity psychosis episodes between the groups. There was no significant difference in any concentration of risperidone, 9-OH-risperidone, or active moiety between the groups although the with-CYP2D6*10 group had greater variabilities of these parameters compared to the without-CYP2D6*10 group. There was a lower rate of dopamine supersensitivity psychosis episodes in the without-CYP2D6*10 group (4/15, 26.7%) compared to the with-CYP2D6*10 group (11/21, 52.4%), but the difference was not significant. Although our findings were negative, largely because of the small sample size, these results suggest that (1) patients with an impaired functional allele of CYP2D6 may have higher concentrations of risperidone and its active metabolite and that (2) these patients may experience more frequent dopamine supersensitivity psychosis episodes.
Databáze: MEDLINE