THERAPEUTIC EQUIVALENCE OF RISPERIDONE GIVEN ONCE-DAILY AND TWICE-DAILY IN PATIENTS WITH SCHIZOPHRENIA

A study was conducted to determine whether once-daily administration o f 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 risp eridone at 8 mg once daily or 4 mg twice daily. The primary efficacy m easure was the treatment response rate, defined as a 20% or greater re duction 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 treatme nt 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 Ra ting Scale were observed in both groups, with no significant between-g roup differences. Extrapyramidal Symptom Rating Scale scores did not d iffer significantly between groups. There were no clinically relevant changes in vital signs, electrocardiograms, or clinical laboratory tes t results in either group. Gradual dosage titration over the first 3 d ays of treatment was well-tolerated in both groups. The median trough plasma concentrations of risperidone, 9-hydroxyrisperidone, and risper idone plus 9-hydroxyrisperidone were significantly lower with once-dai ly than with twice-daily administration; median plasma concentrations measured within the first 8 hours after administration tended to be hi gher with once-daily administration. These differences did not affect the safety and efficacy of risperidone. Risperidone given once daily a t 8 mg is as effective as twice-daily administration of 4 mg in the tr eatment of acute exacerbations of schizophrenia. Both regimens were eq ually well-tolerated.