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Relationship between plasma risperidone and 9-hydroxyrisperidone concentrations and clinical response in patients with schizophrenia

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Abstract.

Rationale: Evaluation of relationships between serum antipsychotic drug concentrations and clinical response may provide valuable information for rational dosage adjustments. For risperidone, this relationship has been little investigated to date. Objective: To assess the relationship between plasma concentrations of risperidone and its active 9-hydroxy-metabolite (9-OH-risperidone) and clinical response in schizophrenic patients who experienced an acute exacerbation of the disorder. Methods: Forty-two patients (30 males, 12 females, age 24–60 years) were given risperidone at dosages ranging from 4 to 9 mg/day for 6 weeks. The design of the study was open and risperidone dosage could be adjusted individually according to clinical response. Steady-state plasma concentrations of risperidone and its 9-hydroxy-metabolite were measured after 4 and 6 weeks using a specific HPLC assay. Psychopathological state was assessed at baseline and at weeks 2, 4, and 6 by means of the positive and negative syndrome scale (PANSS), and patients were considered responders if they showed a greater than 20% reduction in total PANSS score at final evaluation compared with baseline. Results: Mean plasma concentrations of risperidone, 9-OH-risperidone, and active moiety (sum of risperidone and 9-OH-risperidone concentrations) did not differ between responders (n=28) and non-responders (n=14). No correlation between plasma levels and percent decrease in total PANSS score was found for risperidone (rs=–0.187, NS), 9-OH-risperidone (rs=0.246, NS), and active moiety (rs=0.249, NS). Active moiety concentrations in plasma were higher (P<0.001) in patients developing clinically significant parkinsonian symptoms (n=7) than in those with minimal (n=7) or no drug-induced parkinsonism (n=28). Conclusions: In chronic schizophrenic patients experiencing an acute exacerbation of the disorder, plasma levels of risperidone and its active metabolite correlate with the occurrence of parkinsonian side effects, whereas no significant correlation appears to exist with the degree of clinical improvement.

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Spina, E., Avenoso, A., Facciolà, G. et al. Relationship between plasma risperidone and 9-hydroxyrisperidone concentrations and clinical response in patients with schizophrenia. Psychopharmacology 153, 238–243 (2001). https://doi.org/10.1007/s002130000576

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  • DOI: https://doi.org/10.1007/s002130000576

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