Fine-tuning risperidone dosage for acutely exacerbated schizophrenia: clinical determinants.

RATIONALE: Risperidone doses for acute schizophrenia were rather high in most recent studies. OBJECTIVES: We tested a hypothesis that fine-tuning risperidone dosage to relieve side effects still yields efficacy. Clinical factors influencing the dosing were also determined. METHODS: One hundred and forty-six schizophrenia inpatients with acute exacerbation entered a prospective, 6-week, repeated measures study. Risperidone doses were titrated to 6 mg/day (if tolerable) within 7 days, but were lowered thereafter if adverse reactions appeared. Efficacy and safety were measured biweekly. RESULTS: Forty-eight patients tolerated the 6-mg/day target dose well, while the other 98 received lower final doses (mean+/-SD=3.4+/-0.9 mg/day) to curtail adverse effects. At endpoint, 64.3% of the low-dose patients and 43.8% of the high-dose subjects responded to treatment [>/=20% reduction in the Positive and Negative Syndrome Scale (PANSS) total score] ( P=0.018). In detail, the low-dose individuals were significantly superior in percentage changes in the PANSS total and general-subscale scores at endpoint. The low-dose group also tended to improve more (albeit statistically insignificantly) in the PANSS positive and negative subscales and other efficacy measures. Compared to the patients with undifferentiated subtype, those with disorganized subtype received higher dosage by 0.90 mg/day, after controlling for other variables ( P=0.008). Paranoid subtype was similar to undifferentiated subtype in drug doses. Patients with longer illness duration also showed a trend to use higher dosage ( P=0.078). CONCLUSIONS: These findings suggest that dosage adjustment to diminish side effects does not compromise risperidone response and that disorganized patients and perhaps patients with longer illness duration are prone to receive larger doses.

Influences of patient-related variables on risperidone efficacy for acutely exacerbated schizophrenia: analyses with rigorous statistics.

Response predictors of risperidone or other newer atypical antipsychotics for schizophrenia treatment remain unclear. This study aimed to investigate the influence of patient demographics on risperidone efficacy for schizophrenia. One hundred twenty-one newly hospitalized patients who had schizophrenia with acute exacerbation entered this prospective, 6-week risperidone trial. The target dose was 6 mg/day, or lower in case of side effects. Consequently, the mean +/- SD dose remained quite stable after week 2 and reached 4.4 +/- 1.3 mg/day at week 6. Efficacy and side effect assessments were conducted biweekly. The mean total score of the Positive and Negative Syndrome Scale (PANSS) declined during the trial, particularly within the first 4 weeks. Further, of the various efficacy scores (and their natural logarithm values) collected, only the logarithm of the PANSS total score was selected to serve as the response value, because it was normally distributed and thus suitable for regression analyses. After adjusting the effects of treatment duration (weeks 0-6) and other patient-related variables with the generalized estimating equation method, each 1-week increase in duration of prior hospitalizations raised the PANSS total by 0.04% (p = 0.002) and each 1-year increment in the education duration decreased the PANSS by 0.94% (p = 0.04). Gender, age, age at illness onset, duration of illness, diagnosis subtype, or number of prior hospitalizations, however, did not significantly impact the response value. These preliminary results suggest that longer hospitalization duration and shorter education predict higher symptomatology. Further studies with longer observation and larger samples in not only acutely ill patients but also other populations (e.g., first-episode patients) are warranted.