A cross-sectional study of plasma risperidone levels with risperidone long-acting injectable: Implications for dopamine D 2 receptor occupancy during maintenance treatment in schizophrenia

Saeko Ikai, Gary Remington, Takefumi Suzuki, Hiroyoshi Takeuchi, Takashi Tsuboi, Ryosuke Den, Jinichi Hirano, Kenichi Tsunoda, Masahiko Nishimoto, Koichiro Watanabe, Masaru Mimura, David Mamo, Hiroyuki Uchida

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Objective: While 65%-80% occupancy of dopamine D 2 receptors with antipsychotics has been proposed to achieve optimal therapeutic response during acute treatment of schizophrenia, it remains unclear as to whether it is also necessary to maintain D 2 receptor occupancy within this "safe" window for ongoing maintenance treatment. The data are especially scarce for long-acting antipsychotic formulations. Method: Clinically stable patients with schizophrenia (DSM-IV) receiving a stable dose of risperidone long-acting injectable (LAI) as antipsychotic monotherapy for at least 3 months and free of any psychiatric hospitalization over the past 6 months were included. Dopamine D 2 receptor occupancy levels at trough were estimated from plasma concentrations of risperidone plus 9-hydroxyrisperidone immediately before the intramuscular injection of risperidone LAI, using a 1-site binding model derived from our previous positron emission tomography data. This study was conducted from October to December 2011. Results: 36 patients were included in this study (mean ± SD age, 49.3 ± 14.0 years; mean ± SD dose and interval of injections, 38.2 ± 11.6 mg and 16.5 ± 14.0 days, respectively). Mean ± SD D 2 receptor occupancy was 62.1% ± 15.4%; 52.8% of the subjects (n = 19) did not demonstrate an occupancy of ≥ 65%. On the other hand, 13.9% (n = 5) showed a D 2 occupancy as high as over 80% at the estimated trough. Conclusions: More than half of patients taking risperidone LAI maintained clinical stability without achieving continuous blockade of dopamine D 2 receptors ≥ 65% in real-world clinical settings. Results suggest that sustained dopamine D 2 receptor occupancy levels of ? 65% may not be necessary for maintenance treatment with risperidone LAI in schizophrenia.

Original languageEnglish
Pages (from-to)1147-1152
Number of pages6
JournalJournal of Clinical Psychiatry
Volume73
Issue number8
DOIs
Publication statusPublished - 2012 Aug

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Risperidone
Dopamine
Schizophrenia
Cross-Sectional Studies
Injections
Antipsychotic Agents
Therapeutics
Intramuscular Injections
Diagnostic and Statistical Manual of Mental Disorders
Positron-Emission Tomography
Psychiatry
Hospitalization
Binding Sites
Plasma
Dose

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Arts and Humanities (miscellaneous)

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A cross-sectional study of plasma risperidone levels with risperidone long-acting injectable : Implications for dopamine D 2 receptor occupancy during maintenance treatment in schizophrenia. / Ikai, Saeko; Remington, Gary; Suzuki, Takefumi; Takeuchi, Hiroyoshi; Tsuboi, Takashi; Den, Ryosuke; Hirano, Jinichi; Tsunoda, Kenichi; Nishimoto, Masahiko; Watanabe, Koichiro; Mimura, Masaru; Mamo, David; Uchida, Hiroyuki.

In: Journal of Clinical Psychiatry, Vol. 73, No. 8, 08.2012, p. 1147-1152.

Research output: Contribution to journalArticle

Ikai, Saeko ; Remington, Gary ; Suzuki, Takefumi ; Takeuchi, Hiroyoshi ; Tsuboi, Takashi ; Den, Ryosuke ; Hirano, Jinichi ; Tsunoda, Kenichi ; Nishimoto, Masahiko ; Watanabe, Koichiro ; Mimura, Masaru ; Mamo, David ; Uchida, Hiroyuki. / A cross-sectional study of plasma risperidone levels with risperidone long-acting injectable : Implications for dopamine D 2 receptor occupancy during maintenance treatment in schizophrenia. In: Journal of Clinical Psychiatry. 2012 ; Vol. 73, No. 8. pp. 1147-1152.
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abstract = "Objective: While 65{\%}-80{\%} occupancy of dopamine D 2 receptors with antipsychotics has been proposed to achieve optimal therapeutic response during acute treatment of schizophrenia, it remains unclear as to whether it is also necessary to maintain D 2 receptor occupancy within this {"}safe{"} window for ongoing maintenance treatment. The data are especially scarce for long-acting antipsychotic formulations. Method: Clinically stable patients with schizophrenia (DSM-IV) receiving a stable dose of risperidone long-acting injectable (LAI) as antipsychotic monotherapy for at least 3 months and free of any psychiatric hospitalization over the past 6 months were included. Dopamine D 2 receptor occupancy levels at trough were estimated from plasma concentrations of risperidone plus 9-hydroxyrisperidone immediately before the intramuscular injection of risperidone LAI, using a 1-site binding model derived from our previous positron emission tomography data. This study was conducted from October to December 2011. Results: 36 patients were included in this study (mean ± SD age, 49.3 ± 14.0 years; mean ± SD dose and interval of injections, 38.2 ± 11.6 mg and 16.5 ± 14.0 days, respectively). Mean ± SD D 2 receptor occupancy was 62.1{\%} ± 15.4{\%}; 52.8{\%} of the subjects (n = 19) did not demonstrate an occupancy of ≥ 65{\%}. On the other hand, 13.9{\%} (n = 5) showed a D 2 occupancy as high as over 80{\%} at the estimated trough. Conclusions: More than half of patients taking risperidone LAI maintained clinical stability without achieving continuous blockade of dopamine D 2 receptors ≥ 65{\%} in real-world clinical settings. Results suggest that sustained dopamine D 2 receptor occupancy levels of ? 65{\%} may not be necessary for maintenance treatment with risperidone LAI in schizophrenia.",
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AU - Ikai, Saeko

AU - Remington, Gary

AU - Suzuki, Takefumi

AU - Takeuchi, Hiroyoshi

AU - Tsuboi, Takashi

AU - Den, Ryosuke

AU - Hirano, Jinichi

AU - Tsunoda, Kenichi

AU - Nishimoto, Masahiko

AU - Watanabe, Koichiro

AU - Mimura, Masaru

AU - Mamo, David

AU - Uchida, Hiroyuki

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N2 - Objective: While 65%-80% occupancy of dopamine D 2 receptors with antipsychotics has been proposed to achieve optimal therapeutic response during acute treatment of schizophrenia, it remains unclear as to whether it is also necessary to maintain D 2 receptor occupancy within this "safe" window for ongoing maintenance treatment. The data are especially scarce for long-acting antipsychotic formulations. Method: Clinically stable patients with schizophrenia (DSM-IV) receiving a stable dose of risperidone long-acting injectable (LAI) as antipsychotic monotherapy for at least 3 months and free of any psychiatric hospitalization over the past 6 months were included. Dopamine D 2 receptor occupancy levels at trough were estimated from plasma concentrations of risperidone plus 9-hydroxyrisperidone immediately before the intramuscular injection of risperidone LAI, using a 1-site binding model derived from our previous positron emission tomography data. This study was conducted from October to December 2011. Results: 36 patients were included in this study (mean ± SD age, 49.3 ± 14.0 years; mean ± SD dose and interval of injections, 38.2 ± 11.6 mg and 16.5 ± 14.0 days, respectively). Mean ± SD D 2 receptor occupancy was 62.1% ± 15.4%; 52.8% of the subjects (n = 19) did not demonstrate an occupancy of ≥ 65%. On the other hand, 13.9% (n = 5) showed a D 2 occupancy as high as over 80% at the estimated trough. Conclusions: More than half of patients taking risperidone LAI maintained clinical stability without achieving continuous blockade of dopamine D 2 receptors ≥ 65% in real-world clinical settings. Results suggest that sustained dopamine D 2 receptor occupancy levels of ? 65% may not be necessary for maintenance treatment with risperidone LAI in schizophrenia.

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