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The relationship between plasma clozapine concentration and clinical outcome: a cross-sectional study.
Yada, Yuji; Kitagawa, Kohei; Sakamoto, Shinji; Ozawa, Atsushi; Nakada, Akihiro; Kashiwagi, Hiroko; Okahisa, Yuko; Takao, Soshi; Takaki, Manabu; Kishi, Yoshiki; Yamada, Norihito.
Afiliación
  • Yada Y; Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
  • Kitagawa K; Okayama Psychiatric Medical Center, Okayama, Japan.
  • Sakamoto S; Okayama Psychiatric Medical Center, Okayama, Japan.
  • Ozawa A; Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
  • Nakada A; Kanagawa Psychiatric Center, Kanagawa, Japan.
  • Kashiwagi H; Shizuoka Psychiatric Medical Center, Shizuoka, Japan.
  • Okahisa Y; Department of Forensic Psychiatry, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • Takao S; Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
  • Takaki M; Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
  • Kishi Y; Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
  • Yamada N; Okayama Psychiatric Medical Center, Okayama, Japan.
Acta Psychiatr Scand ; 143(3): 227-237, 2021 03.
Article en En | MEDLINE | ID: mdl-33274435
OBJECTIVE: There is no report that statistically evaluates the therapeutic reference (350-600 ng/ml) and adverse drug reaction (ADR) range (>1000 ng/ml) of clozapine (CLZ) recommended by the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) consensus guidelines in an isolated and large sampling study. METHODS: We administered CLZ to 131 Japanese patients with treatment-resistant schizophrenia in a multicenter cross-sectional study. Plasma CLZ concentrations were assayed by high-performance liquid chromatography using trough sampling. The Brief Psychiatric Rating Scale (BPRS) and severe dose-dependent ADR (sedation, myoclonus, and seizures) were analyzed statistically after adjusting for possible confounders. RESULTS: The daily CLZ dosage showed a moderately positive relationship with the plasma concentration (r = 0.49, p < 0.001). Every 100 ng/ml increase in plasma CLZ concentration improved the total BPRS score 1.95% (95% CI: 0.89-3.01, p < 0.001) and the odds ratio (OR) 1.38 (95% CI: 1.14-1.66, p = 0.001) for BPRS response. Compared with concentrations below 350 ng/ml CLZ, 350-600 ng/ml (11.12%; 95% CI: 2.52-19.72, p = 0.012) and 600-1000 ng/ml (11.05%; 95% CI: 2.40-19.71, p = 0.013) showed significant improvement in the total BPRS score. Dosages above 1000 ng/ml showed greater improvement (25.36%; 95% CI: 13.08-37.64, p < 0.001) of the total BPRS score but more severe ADRs than dosages below 1000 ng/ml (OR: 31.72; 95% CI: 1.04-968.81, p = 0.048). CONCLUSION: The AGNP therapeutic reference range (350-600 ng/ml) is useful, and a dose above 1000 ng/ml is potentially more effective but carries the risk of severe ADRs in the central nervous system.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esquizofrenia / Antipsicóticos / Clozapina Tipo de estudio: Clinical_trials / Guideline / Observational_studies / Prevalence_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Acta Psychiatr Scand Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esquizofrenia / Antipsicóticos / Clozapina Tipo de estudio: Clinical_trials / Guideline / Observational_studies / Prevalence_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Acta Psychiatr Scand Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos