Therapeutic equivalence of risperidone given once daily and twice daily in patients with schizophrenia. The Risperidone Study Group.

Abstract

A study was conducted to determine whether once-daily administration of risperidone was as effective and safe as twice-daily administration. In a double-blind 6-week trial, 211 patients with acute exacerbation according to DSM-III-R criteria were randomly assigned to receive risperidone at 8 mg once daily or 4 mg twice daily. The primary efficacy measure was the treatment response rate, defined as a 20% or greater reduction in total Positive and Negative Syndrome Scale (PANSS) scores. Severity of extrapyramidal symptoms was assessed by the Extrapyramidal Symptom Rating Scale. The percentage of patients who showed a treatment response at endpoint was not significantly different between groups (76%, once-daily; 72%, twice-daily), nor was the median time to first treatment response (14 days, both groups). Significant reductions in PANSS total and subscale scores and PANSS-derived Brief Psychiatric Rating Scale were observed in both groups, with no significant between-group differences. Extrapyramidal Symptom Rating Scale scores did not differ significantly between groups. There were no clinically relevant changes in vital signs, electrocardiograms, or clinical laboratory test results in either group. Gradual dosage titration over the first 3 days of treatment was well-tolerated in both groups. The median trough plasma concentrations of risperidone, 9-hydroxyrisperidone, and risperidone plus 9-hydroxyrisperidone were significantly lower with once-daily than with twice-daily administration; median plasma concentrations measured within the first 8 hours after administration tended to be higher with once-daily administration. These differences did not affect the safety and efficacy of risperidone. Risperidone given once daily at 8 mg is as effective as twice-daily administration of 4 mg in the treatment of acute exacerbations of schizophrenia. Both regimens were equally well-tolerated.