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

Kanahara, Nobuhisaa,,b; Yoshimura, Kensukeb,,c,,d; Nakamura, Miwakob; Oda, Yasunorib; Watanabe, Motokie; Iyo, Masaomib

International Clinical Psychopharmacology: May 2019 - Volume 34 - Issue 3 - p 124–130
doi: 10.1097/YIC.0000000000000257
Original Articles
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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.

aDivision of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University

bDepartment of Psychiatry, Chiba University Graduate School of Medicine

cHealth Care Management Center, Chiba University Hospital

dDepartment of psychiatry, Shoushin-kai Mobara Shinkei-ka Hospital

eDepartment of psychiatry, Shouhaku-kai Fujita Hospital, Chiba, Japan

Received 3 November 2018 Accepted 26 February 2019

Correspondence to Dr Nobuhisa Kanahara, Division of Medical Treatment and Rehabilitation, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chuou-ku, Chiba-shi, Chiba 260–8670, Japan, Tel: +81-43-226-2148; fax: +81-43-226-2150; e-mail: kanahara@faculty.chiba-u.jp

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