Risperidone in Acutely Exacerbated Schizophrenia: Dosing Strategies and Plasma Levels
J Clin Psychiatry 2000;61(3):209-214
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Background: The optimal risperidone dosing
strategy for acute schizophrenia requires elucidation.
Furthermore, plasma levels of risperidone and its active
metabolite (9-hydroxyrisperidone) at a given dose vary greatly
among different individuals. For patients who metabolize
risperidone slowly, a medium dose results in excessively high
plasma levels, which might be related to adverse events and
perhaps poor response. We thus investigated whether dose
reduction to diminish adverse reactions associated with ordinary
risperidone doses could still yield efficacy for acutely
Method: Thirty-one newly hospitalized Chinese
patients with acute exacerbation 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-state plasma levels of risperidone and
9-hydroxyrisperidone were analyzed by high performance liquid
chromatography with ultraviolet detection.
Results: Thirty patients completed the trial. Of
them, 17 tolerated the 6-mg 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 effects. At
endpoint, 92.3% of the 13 low-dose individuals responded to
treatment (20% or more reduction in the total Positive and
Negative Syndrome Scale score), compared with 52.9% of the 17
high-dose subjects (p < .05). No significant between-group
differences were revealed in other minor efficacy measures. Of
note, endpoint plasma levels of the active moiety (risperidone
plus 9-hydroxyrisperidone) were similar between the low- and
high-dose groups (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 of risperidone is
efficacious in treating patients with acute exacerbation of
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 effects still yielded efficacy. The 2 dose groups
were comparable in the endpoint steady-state plasma drug