Acute and continuation risperidone monotherapy in bipolar mania: a 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and haloperidol. Risperidone versus haloperidol in the treatment of chronic schizophrenic patients: a parallel group double-blind comparative trial. Risperidone in treatment-refractory schizophrenia. Risperidone versus haloperidol in the treatment of chronic schizophrenic inpatients: a multicentre double-blind comparative study. Risperidone versus haloperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms: a double-blind, multi-center trial. A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. Risperidone in the treatment of first-episode psychotic patients: a double-blind multicenter study. Risperidone Working Group. Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety. Risperidone: clinical safety and efficacy in schizophrenia.
In a randomized, double-blind trial, patients with acute bipolar mania received 1-6 mg/day of risperidone, 2-12 mg/day of haloperidol, or placebo for 3 weeks, followed by double-blind risperidone or haloperidol for 9 weeks. Of 438 patients, 154 were randomized to risperidone, 144 to haloperidol, and 140 to placebo. The mean+/-S.D. modal doses were 4.2+/-1.7 mg/day of risperidone and 8.0+/-3.6 mg/day of haloperidol during the initial 3-week phase and 4.1+/-1.8 and 7.4+/-3.7 mg/day during the 12-week period. At week 3, mean Young Mania Rating Scale (YMRS) score reductions from baseline were significantly greater in patients receiving risperidone than placebo (p<0.001). Differences between risperidone and haloperidol on this efficacy measure were not significant. Further reductions in YMRS scores were seen in patients receiving risperidone or haloperidol during the subsequent 9 weeks. No unexpected adverse events were reported. Extrapyramidal disorder and hyperkinesias, the most commonly reported adverse events with antipsychotic use, occurred less frequently with risperidone than haloperidol. We conclude that risperidone monotherapy was an effective and well-tolerated treatment for bipolar mania and that efficacy was maintained over the long term. A parallel group double-blind comparative trial was conducted to study the efficacy and safety of risperidone compared with haloperidol. After a one-week wash-out, 35 chronic schizophrenic patients (17 males, 18 females) were randomly assigned to one of two groups for eight weeks of double-blind treatment. The patients' psychopathology was assessed by means of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and the Clinical Global Impression (CGI). Safety assessments included the Extrapyramidal Symptom Rating Scale (ESRS), the UKU Side Effect Rating Scale, vital signs, body weight, ECG and laboratory screening. Thirty-two patients completed the trial: there were 3 dropouts in the risperidone group. The results on the PANSS and CGI indicate that the mean changes from baseline on the total PANSS score and on the total BPRS score were comparable in both treatment groups. The number of patients where a clinical improvement at least 20% reduction in baseline score was also similar in both treatment groups. Risperidone caused less extrapyramidal symptoms and less side effects in UKU scale than haloperidol. No significant ECG changes were induced, no relevant changes in blood pressure or clinical laboratory parameters were observed. This study has demonstrated that the combined serotonin 5-HT2 and dopamine-D2 antagonist risperidone is an antipsychotic as potent as haloperidol. Risperidone causes less extrapyramidal symptoms, and is better tolerated than haloperidol. The purpose of this study was to evaluate the clinical safety and efficacy of risperidone compared to haloperidol in patients with treatment-refractory schizophrenia.
                Sixty-seven medication-unresponsive subjects were randomly assigned to treatment with risperidone (N = 34) or haloperidol (N = 33). After a 3-7 day-placebo washout period, there was a 4-week, double-blind, fixed-dose comparison trial that was followed by a 4-week, flexible-dose phase. Measures of clinical change were quantified by standard psychopathologic and neuromotor instruments.
                Risperidone demonstrated clinical efficacy superior to that of haloperidol on the total Brief Psychiatric Rating Scale (BPRS) after the first 4 weeks of treatment. Risperidone did not show any advantage over haloperidol after an additional 4 weeks. Overall improvement on the BPRS at 4 weeks was significantly better for the risperidone group (24%) than for the haloperidol group (11%). Risperidone-treated subjects were significantly less likely than haloperidol-treated subjects to require concomitant anticholinergic medication after 4 weeks (20% versus 63%); they also had significantly les observable akathisia (24% versus 53%) and significantly less severe tardive dyskinesia. Baseline characteristics that correlated significantly with risperidone response were positive symptoms, conceptual disorganization, akathisia, and tardive dyskinesia.
                Risperidone was better tolerated and more effective in a subset of patients with treatment-refractory schizophrenia. Positive psychotic symptoms and extrapyramidal side effects at baseline appear to be powerful predictors of subsequent response to risperidone. Forty-four chronic schizophrenic inpatients participated in this multicentre 12-week parallel-group double-blind trial. After a run-in period of 2 weeks and a single-blind placebo wash-out of 1 week, they were randomly assigned to treatment with either the serotonin2 and dopamine-D2 antagonist risperidone or haloperidol. Two patients were excluded from the efficacy analysis. Five patients dropped out in the haloperidol group and 1 in the risperidone group. At the end of the trial, the mean daily dose was 12 mg for risperidone and 10 mg for haloperidol. The risperidone group showed greater improvement on the Positive and Negative Syndrome Scale for Schizophrenia, the Schedule for Affective Disorders and Schizophrenia-change version, and the Nurses' Observation Scale for Inpatient Evaluation. The improvement of negative symptoms was more pronounced in the risperidone group until week 8 of double-blind treatment. The consumption of antiparkinsonian medication was 10 times lower with risperidone. Both drugs were well tolerated and the laboratory, endocrinological and cardiovascular safety parameters were comparable. This study suggests that risperidone is comparable to haloperidol as an antipsychotic, but that it has a safer EPS profile. A randomized, double-blind, multi-center trial was started to compare the severity of extrapyramidal symptoms (EPS) during risperidone and haloperidol treatment in schizophrenic patients who had disturbing EPS during their previous neuroleptic treatment. Additional objectives of this trial were comparing the antipsychotic effectiveness of the two treatments and the use of antiparkinsonian medication.
                Effects of flexible doses of risperidone and haloperidol were compared in 77 psychotic patients (83% with chronic schizophrenia) with disturbing neuroleptic-induced EPS (risperidone 40 patients, haloperidol 37). The trial was completed by 47 patients: 25 in the risperidone group (12 women, 13 men), and 22 in the haloperidol group (10 women, 12 men).
                An adequate antipsychotic effect was obtained in most patients by both treatments. The primary aim of this trial was comparing parkinsonism measured with the extrapyramidal syndrome rating scale (ESRS) during treatment with risperidone and haloperidol. Two primary parameters were selected: the change from baseline to the worst score during treatment of ESRS II (parkinsonism) and ESRS VI (clinical global impression of severity of parkinsonism). The CGI of severity of parkinsonism was better with risperidone (P=0.025), while the parkinsonism total score tended to be better with risperidone (P<0. 10). Before the double-blind treatment, 34 (of the 77) had used antiparkinson medication (risperidone 18, haloperidol 16). During the double-blind treatment phase, 21 patients had used antiparkinson medication (risperidone 11, haloperidol 10). The larger reduction of parkinsonism in the risperidone group was not due to a difference in the use of anti-parkinsonian medication.
                In this group of schizophrenic patients with disturbing EPS during previous neuroleptic treatment, a stronger reduction of parkinsonism was observed with risperidone than with haloperidol. 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. An international, multicenter, double-blind study was conducted in 183 patients with a first psychotic episode (provisional schizophreniform disorder or schizophrenia; DSM-III-R) treated with flexible doses of risperidone or haloperidol for 6 weeks. At endpoint, 63 percent of risperidone-treated patients and 56 percent of haloperidol-treated patients were clinically improved (> or = 50% reduction in Positive and Negative Syndrome Scale total scores). Risperidone was better tolerated than haloperidol: the severity of extrapyramidal symptoms was significantly lower in the risperidone-treated patients; significantly fewer risperidone-treated patients required antiparkinsonian medication; and significantly fewer discontinued treatment because of adverse events. A post hoc analysis revealed that low doses of these antipsychotics were efficacious in some patients. Furthermore, the severity of extrapyramidal symptoms and the use of antiparkinsonian medications were significantly lower in patients receiving low doses (maximum, < or = 6 mg/day) than high doses (maximum, > 6 mg/day) of risperidone or haloperidol. These findings are consistent with the suggestion that patients with a first psychotic episode may require low doses of antipsychotic medications. Studies designed specifically to compare low and high doses of antipsychotics are warranted to help optimize treatment for these patients. The study assessed the efficacy and safety of risperidone as an adjunctive agent to mood stabilizers in the treatment of acute mania.
                This 3-week randomized, double-blind, placebo-controlled study included 156 bipolar disorder patients with a current manic or mixed episode who received a mood stabilizer (lithium or divalproex) and placebo, risperidone, or haloperidol. The primary efficacy measure was the Young Mania Rating Scale. Other assessments used the Brief Psychiatric Rating Scale, the Clinical Global Impression scale, and safety measures.
                The trial was discontinued by 25 (49%) of the 51 placebo group patients, 18 (35%) of the 52 risperidone group patients, and 28 (53%) of the 53 haloperidol group patients. Mean modal doses were 3.8 mg/day (SD=1.8) of risperidone and 6.2 mg/day (SD=2.9) of haloperidol. Significantly greater reductions in Young Mania Rating Scale scores at endpoint and over time were seen in the risperidone group and in the haloperidol group, compared with the placebo group. Young Mania Rating Scale total scores improved with risperidone and with haloperidol both in patients with psychotic features and in those without psychotic features at baseline. Extrapyramidal Symptom Rating Scale total scores at endpoint were significantly higher in the haloperidol patients than in the placebo patients. Antiparkinsonian medications were received by 8%, 17%, and 38% of patients in the placebo, risperidone, and haloperidol groups, respectively.
                Risperidone plus a mood stabilizer was more efficacious than a mood stabilizer alone, and as efficacious as haloperidol plus a mood stabilizer, for the rapid control of manic symptoms and was well tolerated. Risperidone represents a unique pharmacology of potent antagonism of both serotonin and dopamine receptors. In a randomized, parallel-group, double-blind trial of risperidone vs. haloperidol and placebo in 36 schizophrenic patients in acute exacerbation, risperidone showed a quicker onset of antipsychotic activity than did haloperidol. Risperidone treatment was statistically superior to placebo, with a trend toward superiority to haloperidol. Risperidone did not differ from placebo on assessment scales of extrapyramidal side effects, but produced significantly less than did haloperidol. There were no major adverse reactions associated with risperidone use, but it was noted to reduce the signs of tardive dyskinesia. This study suggests that risperidone may offer a superior side-effect profile, and possibly greater efficacy, than a standard neuroleptic such as haloperidol.
Risperidone, as monotherapy and adjunctive treatment, is effective in reducing manic symptoms. The main adverse effects are weight gain, extrapyramidal effects and sedation. Risperidone is comparable in efficacy to haloperidol. 
Higher quality trials are required to provide more reliable and precise estimates of its costs and benefits.