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

Risperidone doses for acute schizophrenia were rather high in most recent studies.

We tested a hypothesis that fine-tuning risperidone dosage to relieve side effects still yields efficacy. Clinical factors influencing the dosing were also determined.

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.

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).

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.