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

Rationale: Evaluation of relationships between serum antipsychotic drug con centrations and clinical response may provide valuable information for rati onal 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-ri speridone) and clinical response in schizophrenic patients who experienced an acute exacerbation of the disorder. Methods: Forty-two patients (30 male s, 12 females, age 24-60 years) were given risperidone at dosages ranging f rom 4 to 9 mg/day for 6 weeks. The design of the study was open and risperi done dosage could be adjusted individually according to clinical response. Steady-state plasma concentrations of risperidone and its 9-hydroxymetaboli te were measured after 4 and 6 weeks using a specific HPLC assay. Psychopat hological 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 cons idered responders if they showed a greater than 20% reduction in total PANS S score at final evaluation compared with baseline. Results: Mean plasma co ncentrations of risperidone, 9-OH-risperidone, and active moiety (sum of ri speridone and 9-OH-risperidone concentrations) did not differ between respo nders (n=28) and non-responders (n=14). No correlation between plasma level s and percent decrease in total PANSS score was found for risperidone (r(s) =-0.187, NS), 9-OH-risperidone (r(s)=0.246, NS), and active moiety (r(s)=0. 249, NS). Active moiety concentrations in plasma were higher (P<0.001) in p atients developing clinically significant parkinsonian symptoms (n=7) than in those with minimal (n=7) or no drug-induced parkinsonism (n=28). Conclus ions: In chronic schizophrenic patients experiencing an acute exacerbation of the disorder, plasma levels of risperidone and its active metabolite cor relate with the occurrence of parkinsonian side effects, whereas no signifi cant correlation appears to exist with the degree of clinical improvement.