In a double-blind study, 135 inpatients with a diagnosis of chronic
schizophrenia were randomly assigned to 8 weeks of treatment with one of six parallel treatments:
risperidone (a new central 5-hydroxytryptamine2 and
dopamine D2 antagonist), 2, 6, 10, 16 mg/day;
haloperidol, 20 mg/day; or placebo, after a single-blind placebo washout period. Doses were increased in fixed increments up to a fixed maintenance dose reached after 1 week. On the Clinical Global Impression-Severity of Illness and Improvement, all active medications were superior to placebo except for
risperidone (2 mg) on the Clinical Global Impression-Improvement. On the total Positive and Negative Syndrome Scale (PANSS) score and positive subscale, superiority to placebo was observed for all treatment groups except for
haloperidol and
risperidone (2 mg), which tended to be superior to placebo on total PANSS and the positive subscale, respectively. On the PANSS negative subscale, only
risperidone (6 mg/day) was significantly better than placebo.
Risperidone (6 mg) was superior to
haloperidol on the total PANSS, General Psychopathology, and Brief Psychiatric Rating Scale subscales. Although there was a linear increase in
parkinsonism with increasing
risperidone dosage, there were no statistically significant differences between
risperidone (2, 6, and 16 mg/day) and placebo. At doses of 6 to 16 mg,
risperidone displayed a marked antidyskinetic effect compared with placebo. This effect was more pronounced in patients with severe
dyskinesia. By contrast,
haloperidol produced significantly more
parkinsonism than placebo and
risperidone (2, 6 and 16 mg), with no effect on
tardive dyskinesia. These data suggest that
risperidone, at the optimal therapeutic dose of 6 mg/day, produced significant improvement in both positive and negative symptoms without an increase in
drug-induced parkinsonian symptoms and with a significant beneficial effect on
tardive dyskinesia.