Risperidone in acutely exacerbated schizophrenia: Dosing strategies and plasma levels

Background: The optimal risperidone dosing strategy for acute schizophrenia requires elucidation. Furthermore, plasma levels of risperidone and its ac tive metabolite (9-hydroxyrisperidone) at a given dose vary,greatly among d ifferent individuals. For patients who metabolize risperidone slowly, a med ium dose results in excessively high plasma levels, which might be related to adverse events and perhaps poor response. We thus investigated whether d ose reduction to diminish adverse reactions associated with ordinary risper idone doses could still yield efficacy for acutely exacerbated schizophreni a. Method: Thirty-one newly hospitalized Chinese patients with acute exacerbat ion of schizophrenia (DSM-IV) entered this prospective, 6-week open trial. Risperidone doses were titrated to 6 mg/day (if tolerable) over 3 days, but were lowered thereafter if side effects appeared. Efficacy and side effect assessments were conducted on days 0, 4, 14, 28, and 42. Endpoint steady-s tate plasma levels of risperidone and 9-hydroxyrisperidone were analyzed by high performance liquid chromatography with ultraviolet defection. Results: Thirty patients completed the trial. Of them, 17 tolerated the 6-m g target dose well, while the other 13 received lower final doses (mean +/- SD = 3.6 +/- 0.9 mg, p = .0001) for curtailing treatment-emergent side eff ects. At endpoint, 92.3% of the 13 low-dose individuals responded to treatm ent (20% or more reduction in the total Positive and Negative Syndrome Scal e score), compared with 52.9% of the 17 high-dose subjects (p < .05). No si gnificant between-group differences were revealed in other minor efficacy m easures. Of note, endpoint plasma levels of the active moiety (risperidone plus 9-hydroxyrisperidone) were similar between the low- and high-dose grou ps (40.4 +/- 31.1 ng/mL vs. 49.7 +/- 13.4 ng/mL, NS). Conclusion: The results of this preliminary trial suggest that up to 6 mg o f risperidone is efficacious in treating patients with acute exacerbation o f schizophrenia. Nearly 60% of the patients could tolerate a 6-mg dose. For the other 40%, reducing dosages to 3.6 +/-: 0.9 mg for relieving side effe cts still yielded efficacy. The 2 dose groups were comparable in the endpoi nt steady-state plasma drug concentrations.