Long-term treatment of chronic schizophrenia with risperidone: a study with plasma levels

Abstract

Twenty-four chronic schizophrenic outpatients with a mean age of 37.21 years +/- 9.96 SD were treated with risperidone (RSP) at the dosage of 2-9 mg/die (mean 4.46 mg/die +/- 1.30 SD, mean 0.06 mg/kg +/- 0.01 SD) for a year. Clinical evaluation was assessed with the Brief Psychiatric Rating Scale (BPRS), Positive and Negative Symptoms Scale (PANSS), Extrapyramidal Side Effects Rating Scale (EPSE) and a checklist for Anticholinergic Side Effects (ACS) at T0, then after 1 (T1), 2 (T2), 3 (T3), 6 (T6), 9 (T9) and 12 (T12) months. RSP and 9-hydroxy-risperidone (9OH-RSP) plasma levels were determined at T12 by the HPLC method. BPRS and PANSS mean values showed a significant improvement during the study. No correlation between RSP dosage (mg/kg) and RSP, 9OH-RSP plasma levels or active moiety resulted. A positive correlation between age and active moiety was observed. A positive correlation between RSP and 9OH-RSP plasma levels was observed. A curvilinear relationship between active moiety and PANSS improvement (%) was observed. Patients with the higher PANSS amelioration showed RSP + 9OH-RSP plasma levels ranging from 15 to 30 ng/mL. RSP seems to be quite an effective drug. It seems, however, difficult to devise appropriate dose schedules and plasma level determination seems to be necessary in some cases.

Genetics-Based Population Pharmacokinetics and Pharmacodynamics of Risperidone in a Psychiatric Cohort

“…Several studies investigated the relationship between neurologic symptoms and plasma concentration, with positive [64,1,28,27] or negative results [30,29,31] . In the present study, C min-active moiety was significantly associated with akathisia, tremor and combined with rigidity.…”

“…Conflicting results were however obtained in several studies examining the relationship between risperidone or 9-hydroxyrisperidone concentrations with neurological toxicity [28][29][30][31] .…”

Comparação da bioequivalência de duas formulações da risperidona

“…A RSP ou 3-(2-(4-(6-Fluoro-1,2-benzisoxazol-3-il) piperidino) etil)-6,7,8,9-tetrahidro-2-metil-4H-pirido(1,2-a) pirimidin-4-ona (Figura 4A), é um derivado benzioxazólico com propriedades antagonistas seletivas pelos receptores D 2 e serotoninérgicos (5-HT 2A e 5-HT 7 ) (Mannens et al, 1993;Mauri et al;De Oliveira I e Juruena, 2006). Possui alta afinidade pelos receptores α1 e α2-adrenérgicos e histamínicos H1 (Wong e Van Tol, 2003), e eficácia tanto para os sintomas negativos (apatia, retraimento social) quanto para os positivos (delírios, alucinações) da esquizofrenia (Olesen e Linnet, 1997;Spina et al, 2001;Stip, 2002;Riedel et al, 2005).…”

“…Estudos consideram que uma dose de 4-6 mg/dia geralmente alcança a máxima eficácia (Mauri et al, 2001;Möller, 2005;De Oliveira I e Juruena, 2006).…”

“…Alguns fatores podem influenciar nos níveis séricos da fração ativa, tais como: idade, lesões hepáticas e renais, genótipo da CYP2D6 e administração concomitante de outros medicamentos (Avenoso et al, 2000). No entanto, segundo Mauri et al (2001) a concentração da fração ativa não difere muito entre os indivíduos classificados como metabolizadores rápidos e lentos, isto porque nos metabolizadores rápidos, forma-se uma quantidade maior de 9OH-RSP e menor de RSP inalterada, sendo o inverso verificado nos metabolizadores lentos. Assim sendo, os níveis da fração ativa permanecem os mesmos, só variando a proporção entre a substância inalterada e seu produto de biotransformação (Heykants et al, 1994).…”