Comparison of quetiapine and risperidone in the treatment of schizophrenia: A randomized, double-blind, flexible-dose, 8-week study. Risperidone versus pimozide in Tourette's disorder: a comparative double-blind parallel-group study. Effects of risperidone on conduct and disruptive behavior disorders in children with subaverage IQs. A randomized double-blind 12-week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia. Quetiapine has equivalent efficacy and superior tolerability to risperidone in the treatment of schizophrenia with predominantly negative symptoms. Efficacy and safety of aripiprazole in the acute treatment of schizophrenia in Chinese patients with risperidone as an active control: a randomized trial. Double-blind, placebo-controlled study of risperidone for the treatment of disruptive behaviors in children with subaverage intelligence. International multisite double-blind trial of the atypical antipsychotics risperidone and olanzapine in 175 elderly patients with chronic schizophrenia. Risperidone versus haloperidol in the treatment of chronic schizophrenic patients: a parallel group double-blind comparative trial. A randomized controlled trial of risperidone in the treatment of aggression in hospitalized adolescents with subaverage cognitive abilities. Efficacy and tolerability of ziprasidone versus risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder: an 8-week, double-blind, multicenter trial. Risperidone in the treatment of behavioral disturbances in children and adolescents with borderline intellectual functioning: a double-blind, placebo-controlled pilot trial. Tic reduction with risperidone versus pimozide in a randomized, double-blind, crossover trial. Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. Risperidone: clinical safety and efficacy in schizophrenia. A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder. The impact upon extra-pyramidal side effects, clinical symptoms and quality of life of a switch from conventional to atypical antipsychotics (risperidone or olanzapine) in elderly patients with schizophrenia. A randomized placebo-controlled trial of risperidone for the treatment of aggression, agitation, and psychosis of dementia. Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response. Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison. A comparison of the relative safety, efficacy, and tolerability of quetiapine and risperidone in outpatients with schizophrenia and other psychotic disorders: the quetiapine experience with safety and tolerability (QUEST) study. Risperidone in children with autism and serious behavioral problems. Comparison of olanzapine and risperidone in the treatment of psychosis and associated behavioral disturbances in patients with dementia. Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomised controlled clinical trial. Rapid antimanic effect of risperidone monotherapy: a 3-week multicenter, double-blind, placebo-controlled trial. Amisulpride versus risperidone in the treatment of schizophrenic patients: a double-blind pilot study in Taiwan. Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders. A double-blind study of combination of clozapine with risperidone in patients with schizophrenia: effects on cognition. A double-blind, controlled study of sertindole versus risperidone in the treatment of moderate-to-severe schizophrenia. A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. Issues that may determine the outcome of antipsychotic trials: industry sponsorship and extrapyramidal side effect. Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a randomized double-blind study. The Risperidone Study Group. A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth: a double-blind, randomized, 8-week trial.
To compare the efficacy and tolerability of quetiapine and risperidone in the treatment of schizophrenia.
                In this 8-week, double-blind, multicenter, flexible-dose study, patients with schizophrenia (DSM-IV diagnosis) were randomly assigned to quetiapine (200-800 mg/day) or risperidone (2-8 mg/day). The primary hypothesis was that quetiapine was not inferior to risperidone. The primary efficacy measure was change from baseline in Positive and Negative Syndrome Scale (PANSS) total scores; secondary outcomes included response rate (> or = 40% reduction in PANSS scores), Clinical Global Impression-Change (CGI-C), and cognitive and social functioning. Tolerability assessments included treatment-emergent adverse events and changes in weight, glucose, and prolactin. Patients were recruited from June 2001 to September 2002.
                Patients (N = 673) were randomly assigned to quetiapine (N = 338, mean dose = 525 mg/day) or risperidone (N = 335, mean dose = 5.2 mg/day). The primary analysis demonstrated noninferiority between treatments (p < .05). Improvements with both treatments were comparable on PANSS total, negative, and general psychopathology subscales. Risperidone-treated patients had a significantly (p = .03) greater improvement in PANSS positive subscale score among all patients, but not among completers. Improvements in PANSS response rates, CGI-C, and cognitive function were similar between treatment groups. Changes in serum glucose and weight were minimal and comparable. The rate of extrapyramidal symptom (EPS)-related adverse events was significantly higher with risperidone (22%) than quetiapine (13%; p < .01). Somnolence was more common with quetiapine (26%) than risperidone (20%; p = .04). Prolactin levels increased with risperidone (+35.5 ng/mL), but decreased with quetiapine (-11.5 ng/mL; p < .001).
                Quetiapine and risperidone had broadly comparable clinical efficacy. Both agents improved cognitive and social functioning, and neither had a clinically significant effect on weight or glucose. Somnolence was more common with quetiapine; EPS and elevated prolactin rates were significantly higher with risperidone. The treatment of Tourette's disorder with classical neuroleptics is limited by their side effects. Risperidone is a new efficacious antipsychotic with a low propensity for extrapyramidal side effects. To establish risperidone's therapeutic potential in Tourette's disorder, we studied the safety and efficacy of risperidone in comparison with pimozide in patients with Tourette's disorder diagnosed according to DSM-III-R.
                In a 12-week, multicenter, double-blind, parallel-group study, 26 patients were treated with risperidone (mean daily dose = 3.8 mg), and 24 patients were treated with pimozide (mean daily dose = 2.9 mg).
                There was significant improvement of tics with respect to the Tourette's Symptom Severity Scale (TSSS) for both groups. Forty-one patients completed the study. At endpoint, 54% (14/26) of the risperidone patients and 38% (9/24) of the pimozide patients had only very mild or no symptoms on the global severity rating of the TSSS. Both treatment groups had improved significantly at endpoint in regard to Global Assessment of Functioning and Clinical Global Impressions scale outcomes. Symptoms of anxiety and depressive mood improved significantly from baseline in both groups. Obsessive-compulsive behavior improvement reached significance only in the risperidone group. Although the severity of extrapyramidal side effects was low in both groups, fewer patients in the risperidone group reported extrapyramidal side effects (N = 4) compared with the pimozide group (N = 8). Depression, fatigue, and somnolence were reported as the most prominent side effects in both treatment groups.
                Both drugs were efficacious and well tolerated in patients with Tourette's disorder. Risperidone may become the first-line drug in the treatment of Tourette's disorder owing to a more favorable efficacy and tolerability profile. To determine whether risperidone is effective in reducing symptoms of disruptive behaviors (such as aggression, impulsivity, defiance of authority figures, and property destruction) associated with conduct disorder, oppositional defiant disorder, and disruptive behavior disorder-not otherwise specified in children with subaverage IQs.
                The trial consisted of a 1-week, single-blind, placebo run-in period and was followed by a 6-week, double-blind, placebo-controlled period. One hundred ten children (aged 5-12 years inclusive) with an IQ of 36-84 with a disruptive behavior disorder and a score of at least 24 on the Conduct Problem subscale of the Nisonger Child Behavior Rating Form (NCBRF) were enrolled. Eighty percent of subjects had comorbid attention-deficit/hyperactivity disorder (ADHD). Risperidone doses ranged from 0.02 to 0.06 mg/kg per day. Subjects were rated on the NCBRF, Aberrant Behavior Checklist, Behavior Problems Inventory, Clinical Global Impressions (CGI), modified California Verbal Learning Test (CVLT), and a continuous performance task (CPT).
                The intention-to-treat analysis of risperidone-treated subjects showed a significant (p < .001) reduction in mean scores (from 33.4 at baseline to 17.6 at end point; 47.3% reduction) versus placebo-treated subjects (mean baseline of 32.6 to 25.8 at end point; 20.9% reduction) on the Conduct Problem subscale of the NCBRF. Between-group differences in favor of risperidone were seen as early as week 1 and were significant at all post-baseline visits. Other subscales showed significant improvement with risperidone compared with placebo. CGI scale ratings of improvement showed highly significant gains for risperidone over placebo. A subanalysis demonstrated that the effect of risperidone was unaffected by diagnosis, presence/absence of ADHD, psychostimulant use, IQ status, and somnolence. Risperidone produced no changes on the cognitive variables (CPT/modified CVLT). The most common side effects included somnolence, headache, appetite increase, and dyspepsia. Side effects related to extrapyramidal symptoms were reported in 7 (13.2%) and 3 (5.3%) of the subjects in the risperidone and placebo groups, respectively (p = .245).
                Risperidone appears to be an adequately tolerated and effective treatment in children with subaverage IQs and severe disruptive behaviors such as aggression and destructive behavior. Sexual dysfunction is common in people suffering from schizophrenia and is reported by patients to be a significant reason for medication nonadherence. This report contains data for 27 people with schizophrenia who participated in a randomized double-blind 12-week trial of risperidone (4 mg/day), quetiapine (400 mg/day) or fluphenazine (12.5 mg/day). At baseline and endpoint, subjects were rated on the Changes in Sexual Function Questionnaire (CSFQ), the Prolactin-Related Adverse Event Questionnaire (PRAEQ) and had prolactin levels drawn. Endpoint prolactin levels were 50.6 +/- 40.4, 24.4 +/- 18.5, and 8.2 +/- 4.4 mg/dl for risperidone (N = 12), fluphenazine (N = 9) and quetiapine (N=6), respectively (F = 7.5,df = 2, p = 0.005, controlling for sex). Orgasm quality/ability improved significantly for quetiapine as compared to fluphenazine and risperidone (F = 4.41, df = 2, p = 0.033). Seventy-eight percent of patients on fluphenazine reported sexual dysfunction whereas did only 42 and 50% of those on risperidone and quetiapine. Forty percent of quetiapine patients reported they felt better about their sexuality as compared to previous treatment, as did 55% on risperidone. Conversely, only 13% of fluphenazine subjects reported any improvement. Hormonal problems (menstrual problems, gynecomastia, galactorrhea) were predominately observed in risperidone-treated subjects. Overall, quetiapine was associated with a normalization of prolactin levels and had the greatest benefits among these drugs regarding sexual functioning. Atypical antipsychotics are generally thought to be more effective than conventional agents in treating the negative symptoms of schizophrenia; however, there have been few direct comparisons among atypicals. We therefore investigated risperidone and quetiapine with respect to their efficacy against negative symptoms in a 12-week,double-blind, comparative pilot study involving 44 patients with schizophrenia with predominantly negative symptoms, as defined by Positive and Negative Syndrome Scale (PANSS) scores. Other efficacy measures included the Scale for the Assessment of Negative Symptoms (SANS) and the Clinical Global Impression (CGI) rating scale. Antipsychotic tolerability was assessed using the Simpson-Angus Scale (SAS) and various laboratory measures. Mean doses were 589.7 mg/ day quetiapine and 4.9 mg/day risperidone (observed cases). Both antipsychotics produced significant decreases in PANSS total, positive and negative scores, and SANS scores. Patients receiving risperidone were significantly more likely to experience extrapyramidal symptoms (EPS) [p <0.05], or to require anticholinergic medication (p <0.05), and had significantly higher prolactin levels (p <0.001) than quetiapine-treated patients. In conclusion, there is no significant difference in efficacy between quetiapine and risperidone in alleviating the negative symptoms of schizophrenia. Quetiapine is also well tolerated, with a lower incidence of EPS and prolactin increase than risperidone. Asian populations may differ from other races in response to antipsychotics. Studies of aripiprazole in Asian populations are scarce. This study aimed to investigate the efficacy, safety, and tolerability of aripiprazole in Chinese patients with acute schizophrenia or schizoaffective disorder.
                This 4-week, double-blind, randomized, parallel study was conducted in 5 medical centers in Taiwan between March 2004 and January 2005. A total of 83 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were randomly assigned (with a randomization ratio of 3:2) to 15 mg/day of aripiprazole (N = 49) or 6 mg/day of risperidone (N = 34). Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total, positive, and negative scores and Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement scale scores. Extrapyramidal symptoms (EPS), weight gain, serum prolactin level, QTc interval, and self-reported adverse events were assessed as measures of safety and tolerability.
                Both the aripiprazole and risperidone groups showed statistical improvement from baseline in PANSS total, PANSS positive, PANSS negative, and CGI-S scores at study endpoint (all p < .001). Significant improvement was noted in the first week of treatment for both treatment groups. There were no significant differences in efficacy measures between treatment groups. Aripiprazole showed significantly less EPS liability as assessed by the Simpson-Angus Scale (p < .005) and less serum prolactin level elevation (p < .001) than risperidone. Both groups showed mild weight gain. No patients showed clinically significant QTc interval prolongation in this study.
                Compared with risperidone 6 mg/day, aripiprazole 15 mg/day has comparable efficacy and favorable safety and tolerability profiles in the short-term treatment of Chinese patients with acute schizophrenia. In this group of Chinese patients, the overall response to aripiprazole did not differ from that of white patients.
                ClinicalTrials.gov identifier NCT00283179. The short-term efficacy and safety of risperidone in the treatment of disruptive behaviors was examined in a well-characterized cohort of children with subaverage intelligence.
                In this 6-week, multicenter, double-blind, parallel-group study of 118 children (aged 5-12 years) with severely disruptive behaviors and subaverage intelligence (IQ between 36 and 84, inclusive), the subjects received 0.02-0.06 mg/kg per day of risperidone oral solution or placebo. The a priori primary efficacy measure was the change in score from baseline to endpoint on the conduct problem subscale of the Nisonger Child Behavior Rating Form.
                The risperidone group showed significantly greater improvement than did the placebo group on the conduct problem subscale of the Nisonger Child Behavior Rating Form from week 1 through endpoint (change in score of -15.2 and -6.2, respectively). Risperidone was also associated with significantly greater improvement than placebo on all other Nisonger Child Behavior Rating Form subscales at endpoint, as well as on the Aberrant Behavior Checklist subscales for irritability, lethargy/social withdrawal, and hyperactivity; the Behavior Problems Inventory aggressive/destructive behavior subscale; a visual analogue scale of the most troublesome symptom; and the Clinical Global Impression change score. The most common adverse effects reported during risperidone treatment were headache and somnolence. The extrapyramidal symptom profile of risperidone was comparable to that of placebo. Mean weight increases of 2.2 kg. and 0.9 kg occurred in the risperidone and placebo groups, respectively.
                Risperidone was effective and well tolerated for the treatment of severely disruptive behaviors in children with subaverage IQ. The authors compared the effects of the two most commonly used atypical antipsychotics, risperidone and olanzapine, in elderly patients with schizophrenia.
                In an 8-week, international, double-blind study, patients (outpatients, hospital inpatients, and residents of nursing or boarding homes) were randomly assigned to receive risperidone (1 mg to 3 mg/day) or olanzapine (5 mg to 20 mg/day). The main outcome measures were changes in Positive and Negative Syndrome Scale (PANSS) total scores and rates of extrapyramidal symptoms (EPS).
                Subjects were 175 patients age 60 years or over with schizophrenia or schizoaffective disorder. The mean duration of illness was 36.5 years. Median doses were 2 mg/day of risperidone and 10 mg/day of olanzapine. PANSS total scores and four of the five PANSS factor scores (positive symptoms, negative symptoms, disorganized thoughts, and anxiety/depression) improved significantly at all time-points and at endpoint in both groups; between-treatment differences were not significant. EPS-related adverse events were reported by 9.2% of patients in the risperidone group and 15.9% in the olanzapine group; the between-treatment difference was not significant. Total scores on the Extrapyramidal Symptom Rating Scale were reduced in both groups at endpoint; between-treatment differences were not significant. Clinically relevant weight gain was seen in both groups, but was significantly less frequent in risperidone patients than in olanzapine patients.
                Stable elderly patients with chronic schizophrenia receiving appropriate doses of risperidone or olanzapine over an 8-week period experienced significant reductions in the severity of psychotic and extrapyramidal symptoms, with a relatively low risk of side effects. 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. Risperidone is an atypical antipsychotic drug that blocks dopamine as well as serotonin receptor systems. The present study was designed to examine the efficacy and safety of risperidone in a 6-week double-blind, randomized, parallel-group design in the treatment of aggression in adolescents with a primary diagnosis of DSM-IV disruptive behavior disorders and with subaverage intelligence.
                We randomly assigned 38 adolescents (33 boys; 10 subjects with slightly subaverage IQ, 14 with borderline IQ, and 14 with mild mental retardation), who were hospitalized for treatment of psychiatric disorders associated with severe aggression, to receive risperidone or placebo. The main efficacy measures were the Clinical Global Impressions-Severity of Illness scale (CGI-S), the modified Overt Aggression Scale (OAS-M), and the Aberrant Behavior Checklist (ABC). Side effects were measured using the Extrapyramidal Symptom Rating Scale (ESRS).
                The mean daily dose of risperidone at the end of treatment was 2.9 mg (range, 1.5-4 mg). Risperidone, compared with placebo, was associated with significant improvements on the CGI-S (p < .001) and the at-school ABC overall and hyperactivity scales (p < .05). During a 2-week washout following the 6-week trial, a statistically significant worsening was found in the risperidone group on the CGI-S scale, the OAS-M. and the ABC. Extrapyramidal symptoms were absent or very mild during risperidone treatment. Transient tiredness was present in 11 (58%) of 19 drug-treated subjects. Other untoward effects included sialorrhea, nausea, and slight weight gain (mean = 3.5% of body weight in the risperidone group). No clinically relevant changes were found in laboratory parameters, electrocardiogram, heart rate, or blood pressure.
                These results suggest that risperidone may be effective for severe aggression in adolescents with disruptive behavior disorders and subaverage intelligence, and these results are consistent with reports suggesting its effectiveness for treating severe aggression in adolescents in general. More head-to-head comparisons of antipsychotics are needed to discern the relative efficacy and safety profiles of these compounds. Thus, we compared ziprasidone and risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder.
                Patients with DSM-III-R acute exacerbation of schizophrenia or schizoaffective disorder were randomly assigned to double-blind ziprasidone 40 to 80 mg b.i.d. (N = 149) or risperidone 3 to 5 mg b.i.d (N = 147) for 8 weeks. Primary efficacy measures included Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions-Severity of Illness scale (CGI-S) score; secondary measures included scores on the PANSS negative sub-scale, CGI-Improvement scale (CGI-I), and PANSS-derived Brief Psychiatric Rating Scale (BPRSd) total and core items. Safety assessments included movement disorder evaluations, laboratory tests, electrocardiography, vital signs, and body weight. Efficacy analyses employed a prospectively defined Evaluable Patients cohort. Treatment equivalence was conferred if the lower limit of the 95% confidence interval of the ziprasidone/risperidone ratio of least-squares mean change from baseline was > 0.60. Data were gathered from August 1995 to January 1997.
                Equivalence was demonstrated in PANSS total scores, CGI-S scores, PANSS negative subscale scores, BPRSd total and core item scores, and PANSS total and CGI-I responder rates. Both agents were well tolerated. Risperidone exhibited a significantly higher Movement Disorder Burden (MDB) score (p < .05) and higher incidences of prolactin elevation and clinically relevant weight gain. However, compared with current recommendations, study dosing may have been high for some risperidone-treated patients (mean dose = 7.4 mg/day) and low for some ziprasidone-treated patients (mean dose = 114.2 mg/day).
                Both agents equally improved psychotic symptoms, and both were generally well tolerated, with ziprasidone demonstrating a lower MDB score and less effect on prolactin and weight than risperidone. Risperidone, an antipsychotic agent with combined serotonin (5-HT2A) and dopamine (D2) receptor-blocking properties, is associated with fewer extrapyramidal side effects in adults than conventional neuroleptics. Approved in 1993 for the treatment of schizophrenia, recent studies have highlighted its potential in other conditions, such as the management of behavioral disturbances. This phase II, double-blind, placebo-controlled study evaluated the efficacy and tolerability of risperidone in the treatment of persistent behavioral disturbances in children with borderline intellectual functioning. Thirteen patients (6-14 years) with low IQ (66-85) were enrolled in and completed the 4-week study. Risperidone, in daily doses of > or = 0.01 mg/kg (mean dose at treatment endpoint = 0.05 mg/kg; mean total dose = 1.2 mg/day), was significantly more effective than placebo in improving Aberrant Behavioral Checklist (ABC) symptom cluster scores for irritation (p < 0.05) and hyperactivity (p < 0.01), Clinical Global Impression score (p < 0.05), the Visual Analogue Scale score for individual target symptom (p < 0.001), and Personal Assessment Checklist scores for social relationships (p < 0.05) and occupational attitudes (p < 0.05). In addition, the improvement in total ABC score in the risperidone-treated group was clinically relevant (65% improvement vs. baseline), whereas the placebo-treated patients only improved 7% versus baseline. There was no difference between risperidone- and placebo-treated groups with respect to the occurrence of extrapyramidal side effects, and risperidone was well tolerated. In conclusion, short-term risperidone treatment was well tolerated and significantly more effective than placebo in controlling behavioral disturbances in children with low IQ. To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders.
                This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic motor tic disorder were randomized to 4 weeks of treatment with pimozide or risperidone, followed by the alternate treatment after a 2-week placebo washout. The primary efficacy outcome measure was change in tic severity assessed by the Yale Global Tic Severity Scale (YGTSS). ECG results, weight gain, and side effects were also compared.
                Compared to pimozide treatment, risperidone treatment was associated with significantly lower tic severity scores (YGTSS: baseline 43.3 +/- 17.5, pimozide 34.2 +/- 14.2, risperidone 25.2 +/- 13.6; p =.05). Weight gain during the 4-week treatment periods was greater for risperidone (mean 1.9 kg) than pimozide (1.0 kg). No patient suffered a serious adverse event, but 6 of 19 subjects failed to complete the protocol. Neither medication was associated with ECG changes.
                In this study, risperidone appeared superior to pimozide for tic suppression but was associated with greater weight gain. Aripiprazole is a dopamine D2 receptor partial agonist with partial agonist activity at serotonin 5HT1A receptors and antagonist activity at 5HT2A receptors. This multicenter trial examined the efficacy, safety, and tolerability of aripiprazole in patients with acute exacerbation of schizophrenia or schizoaffective disorder.
                In this 4-week double-blind study, 404 patients were randomized to 20 mg/d (n = 101) or 30 mg/d (n = 101) of aripiprazole, placebo (n = 103), or 6 mg/d of risperidone (n = 99). Efficacy assessments included Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression scores. Safety and tolerability evaluations included extrapyramidal symptoms and effects on weight, prolactin, and corrected QT (QTc) interval.
                Aripiprazole (20 and 30 mg/d) and risperidone (6 mg/d) were significantly better than placebo on all efficacy measures. Separation from placebo occurred at week 1 for PANSS total and positive scores with aripiprazole and risperidone and for PANSS negative scores with aripiprazole. There were no significant differences between aripiprazole and placebo in mean change from baseline in the extrapyramidal symptom rating scales. Mean prolactin levels decreased with aripiprazole but significantly increased 5-fold with risperidone. Mean change in QTc interval did not differ significantly from placebo with any active treatment group. Aripiprazole and risperidone groups showed a similar low incidence of clinically significant weight gain.
                Aripiprazole is effective, safe, and well tolerated for the positive and negative symptoms in schizophrenia and schizoaffective disorder. It is the first non-D2 receptor antagonist with clear antipsychotic effects and represents a novel treatment development for psychotic disorders. 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. The safety and efficacy of risperidone and olanzapine were compared in a double-blind trial that used doses widely accepted in clinical practice.
                Subjects (N=377) who met DSM-IV criteria for schizophrenia or schizoaffective disorder were randomly assigned to receive 2-6 mg/day of risperidone (mean modal dose=4.8 mg/day) or 5-20 mg/day of olanzapine (mean modal dose=12.4 mg/day) for 8 weeks.
                The two study groups were similar at baseline except that the olanzapine group was slightly younger than the risperidone group. Seventy-five percent of the participants completed the trial, with no between-treatment differences in the proportion of dropouts. Similar proportions of the risperidone and olanzapine groups reported extrapyramidal symptoms (24% and 20%, respectively). Severity of extrapyramidal symptoms was low in both groups, with no between-group differences. Total Positive and Negative Syndrome Scale scores and scores on the five Positive and Negative Syndrome Scale factors were improved in both groups at week 8 (subjects who completed the study) and endpoint (all subjects, including dropouts). There were overall between-treatment differences in efficacy. Comparison of individual factors found no significant differences at endpoint; at week 8, however, improvements on Positive and Negative Syndrome Scale factors for positive symptoms and anxiety/depression were greater with risperidone than olanzapine. An increase in body weight of > or =7% was seen in 27% of olanzapine participants and 12% of risperidone participants.
                Both treatments were well tolerated and efficacious. The frequency and severity of extrapyramidal symptoms were similar in the two treatment groups. Greater reductions in severity of positive and affective symptoms were seen with risperidone than with olanzapine treatment among study completers. There was no measure on which olanzapine was superior. Greater weight gain was associated with olanzapine than with risperidone treatment. Atypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance, but have similar efficacy to conventional antipsychotics. Trials in the elderly have been either retrospective, small, of short duration or of a single-arm design.
                To demonstrate the effects upon motor side-effects, efficacy, safety and quality of life (QOL) of switching elderly patients with schizophrenia from conventional antipsychotics to olanzapine or risperidone.
                Elderly patients with schizophrenia were randomly allocated to olanzapine or risperidone and followed through an open-label crossover period. Between and within group intention to treat analyses were conducted.
                66 patients were randomised (mean age 69.6 [SD +/- 6.2]). Four (11.8%) patients on olanzapine and 8 (26.7%) patients on risperidone failed to complete the crossover because of treatment failure [Odds Ratio (OR) = 2.73[0.73-10.2] p = 0.14]. The mean doses upon completion of switching in each arm were 9.9 mg (SD = 4.2) and 1.7 mg (SD = 1.2) for olanzapine and risperidone respectively. In both arms there was improvement in Parkinsonism, though only olanzapine was associated with a reduction in dyskinetic symptoms. The Brief Psychiatric Rating Scale, Scale for the assessment of Negative Symptoms and Montgomery and Asberg Depression Rating Scale scores all improved through the crossover period in both arms with no between group differences. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the World Health Organisation-Quality Of Life [Brief] (WHO-QOL-BREF) scale ( p = 0.02). Patients in the olanzapine arm also demonstrated improvement from baseline in the WHO-QOL-BREF physical, psychological and health satisfaction domains, but risperidone had no effect on any Quality of Life (QOL) measure.
                After switching from a conventional antipsychotic, olanzapine and risperidone were associated with improvement in core symptoms of schizophrenia and motor side effects. Subjects switched to olanzapine were more likely to complete the switching process and show an improvement in psychological QOL.
                Copyright 2003 John Wiley & Sons, Ltd. This randomized, double-blind, placebo-controlled trial examined the efficacy and safety of risperidone in the treatment of aggression, agitation, and psychosis in elderly nursing-home patients with dementia.
                Elderly patients with a DSM-IV diagnosis of dementia of the Alzheimer's type, vascular dementia, or a combination of the 2 (i.e., mixed dementia) and significant aggressive behaviors were randomized to receive, for a period of 12 weeks, a flexible dose of either placebo or risperidone solution up to a maximum of 2 mg/day. Outcome measures were the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale, and the Clinical Global Impression of Severity (CGI-S) and of Change (CGI-C) scales.
                A total of 345 patients were randomized to treatment with risperidone or placebo, and 337 patients received at least one dose of study drug. The trial was completed by 67% of patients in the placebo group and 73% of patients in the risperidone group. The mean +/- SE dose of risperidone was 0.95 +/- 0.03 mg/day. The primary endpoint of the study, the difference from baseline to endpoint in CMAI total aggression score, showed a significant reduction in aggressive behavior for risperidone versus placebo (p <.001). A similar improvement was also seen for the CMAI total non-aggression subscale (p <.002) and for the BEHAVE-AD total (p <.001) and psychotic symptoms subscale (p =.004). At endpoint, the CGI-S and the CGI-C scores indicated a significantly greater improvement with risperidone compared with placebo (p <.001). Overall, 94% and 92% of the risperidone and placebo groups, respectively, reported at least 1 adverse event. Somnolence and urinary tract infection were more common with risperidone treatment, whereas agitation was more common with placebo. There was no significant difference in the number of patients who reported extrapyramidal symptoms between the risperidone (23%) and placebo (16%) groups.
                Treatment with low-dose (mean = 0.95 mg/day) risperidone resulted in significant improvement in aggression, agitation, and psychosis associated with dementia. Clozapine and risperidone were the first two "second-generation" antipsychotic drugs approved for schizophrenia. There is currently little information about their comparative efficacy from head-to-head clinical trials. The purpose of this study was to examine the comparative efficacy of clozapine and risperidone for positive and negative symptoms, depression, parkinsonian side effects, and indexes of neuroendocrine function in schizophrenic patients who met a priori criteria for partial response to traditional neuroleptic agents.
                After a baseline fluphenazine treatment period, 29 patients participated in a 6-week, double-blind, parallel-group comparison of the effects of these agents.
                Clozapine was superior to risperidone for positive symptoms and parkinsonian side effects, but there were no significant differences between the drugs on two measures of negative symptoms, Brief Psychiatric Rating Scale total scores, and depression scores. The clozapine patients, but not the risperidone patients, demonstrated significant reductions from the fluphenazine baseline in positive symptoms, total symptoms, and depression. In addition, clozapine produced fewer effects on plasma prolactin than risperidone or fluphenazine. The mean daily doses during week 6 of the trial were 403.6 mg of clozapine and 5.9 mg of risperidone.
                The findings from this study indicate that these drugs have both important differences and similarities in their comparative efficacy in chronically ill, partially responsive patients with schizophrenia. Further research on second-generation antipsychotic drugs in this patient population that addresses key methodological issues, such as optimal dose and treatment duration, are needed. This 52-week randomized, double-blind, flexible-dose, multicenter study evaluated the overall effectiveness (as measured by treatment discontinuation rates) of olanzapine, quetiapine, and risperidone in patients early in the course of psychotic illness.
                Patients were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) administered in twice-daily doses. Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks (primary outcome measure) based on a prespecified noninferiority margin of 20%.
                A total of 400 patients were randomly assigned to treatment with olanzapine (N=133), quetiapine (N=134), or risperidone (N=133). The mean modal prescribed daily doses were 11.7 mg for olanzapine, 506 mg for quetiapine, and 2.4 mg for risperidone. At week 52, all-cause treatment discontinuation rates were 68.4%, 70.9%, and 71.4% for olanzapine, quetiapine, and risperidone, respectively. Reductions in total score on the Positive and Negative Syndrome Scale (PANSS) were similar for the three treatment groups, but reductions in PANSS positive subscale scores were greater in the olanzapine group (at 12 weeks and at 52 weeks or withdrawal from study) and the risperidone group (at 12 weeks). The most common elicited adverse events for olanzapine were drowsiness (53%), weight gain (51%), and insomnia (38%); for quetiapine, drowsiness (58%), increased sleep hours (42%), and weight gain (40%); and for risperidone, drowsiness (50%), menstrual irregularities in women (47%), and weight gain (41%).
                Olanzapine, quetiapine, and risperidone demonstrated comparable effectiveness in early-psychosis patients, as indicated by similar rates of all-cause treatment discontinuation. The few published direct comparative studies of the tolerability and efficacy of atypical antipsychotic agents were performed in relatively homogeneous populations that may not be typical of patients seen in clinical practice.
                The Quetiapine Experience with Safety and Tolerability (QUEST) study compared the relative safety, tolerability, and efficacy of quetiapine and risperidone in outpatients with a broad range of psychotic symptoms.
                This was a multicenter, 4-month, open-label, randomized clinical trial. Patients were randomized in a 3:1 ratio to receive quetiapine or risperidone. Doses were adjusted to maximize efficacy and to minimize adverse events. Extrapyramidal symptoms (EPS) were assessed with an EPS checklist; adverse events were recorded. Efficacy was assessed using the Clinical Global Impression (CGI) scale, Positive and Negative Symptom Scale (PANSS), and Hamilton Rating Scale for Depression (HAM-D).
                A total of 728 patients were randomized, 553 to quetiapine and 175 to risperidone. Mean prescribed doses over the study period were 253.9 mg/d quetiapine and 4.4 mg/d risperidone. At the end of 4 months, EPS declined in both treatment groups, but quetiapine-treated patients were significantly less likely to require dose adjustment or concurrent anti-EPS medication (P < 0.001). The most common adverse events in the quetiapine and risperidone groups were somnolence (31.3% and 15.4%, respectively), dry mouth (14.5% and 6.9%), and dizziness (12.7% and 6.9%). Overall, tolerance to side effects with the 2 drugs, measured by dropout rates, was comparable. At each visit, a higher percentage of quetiapine-treated patients showed improvement on the CGI scale, but there were no significant between-group differences on the PANSS. At end point, quetiapine-treated patients had significantly lower HAM-D scores (P = 0.028).
                The results of this study suggest that quetiapine is as effective as risperidone for the treatment of psychotic symptoms, is more effective for depressive symptoms, may have a more favorable EPS profile, and has comparable overall tolerability. Atypical antipsychotic agents, which block postsynaptic dopamine and serotonin receptors, have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances. However, data on the safety and efficacy of atypical antipsychotic agents in children are limited.
                We conducted a multisite, randomized, double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior in children 5 to 17 years old. The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions - Improvement (CGI-I) scale at eight weeks.
                A total of 101 children (82 boys and 19 girls; mean [+/-SD] age, 8.8+/-2.7 years) were randomly assigned to receive risperidone (49 children) or placebo (52). Treatment with risperidone for eight weeks (dose range, 0.5 to 3.5 mg per day) resulted in a 56.9 percent reduction in the Irritability score, as compared with a 14.1 percent decrease in the placebo group (P<0.001). The rate of a positive response, defined as at least a 25 percent decrease in the Irritability score and a rating of much improved or very much improved on the CGI-I scale, was 69 percent in the risperidone group (34 of 49 children had a positive response) and 12 percent in the placebo group (6 of 52, P<0.001). Risperidone therapy was associated with an average weight gain of 2.7+/-2.9 kg, as compared with 0.8+/-2.2 kg with placebo (P<0.001). Increased appetite, fatigue, drowsiness, dizziness, and drooling were more common in the risperidone group than in the placebo group (P<0.05 for each comparison). In two thirds of the children with a positive response to risperidone at eight weeks (23 of 34), the benefit was maintained at six months.
                Risperidone was effective and well tolerated for the treatment of tantrums, aggression, or self-injurious behavior in children with autistic disorder. The short period of this trial limits inferences about adverse effects such as tardive dyskinesia.
                Copyright 2002 Massachusetts Medical Society The authors compared efficacy of olanzapine versus placebo and risperidone as measured by the Neuropsychiatric Inventory and Clinical Global Impression-Severity of Psychosis scale in patients with dementia-related psychosis.
                Patients with moderate-to-severe psychotic symptoms associated with dementia were recruited from outpatient or residential settings and randomly assigned to 10-week, double-blind, flexible-dose treatment with olanzapine (N=204; 2.5 mg-10 mg/day; mean: 5.2 mg/day), risperidone (N=196; 0.5 mg-2 mg/day; mean: 1.0 mg/day) or placebo (N=94).
                Most measures of neuropsychiatric functioning improved in all treatment groups, including the placebo group, and no significant treatment differences occurred. Overall discontinuation was lowest in the placebo group, and the olanzapine group had a significantly higher incidence of discontinuation due to adverse events (16.2%) relative to placebo (3.2%) and risperidone (8.7%) groups. Treatment-emergent extrapyramidal symptoms were more numerous for risperidone- than placebo- or olanzapine-treated patients. Abnormally high prolactin levels occurred in 78.0% of risperidone patients, compared with 16.7% for olanzapine and 5.0% for placebo. The incidence of weight gain greater than 7% from baseline was higher in the olanzapine group relative to risperidone, but neither active-treatment group showed a statistical difference from placebo (1.1%). No other statistically significant and clinically relevant differences were seen for any other vital sign, electrocardiographic measure, or laboratory hematology and chemistry, including glucose, except for cholesterol, which decreased from baseline to endpoint in both active-treatment groups.
                Patients' neuropsychiatric functioning improved with olanzapine, risperidone, and placebo treatment. There was a substantial response in the placebo group, and no significant differences emerged among treatments. Patients suffering from schizophrenic psychoses sometimes insufficiently respond to antipsychotic monotherapy and then combination approaches are preferred. We aimed in validating the add-on of ziprasidone and risperidone to clozapine, and we performed a randomised head-to-head trial. Patients with partial response to clozapine were randomly attributed to augmentation with ziprasidone (n = 12) or risperidone (n = 12). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Depression Scale (HAMD), the Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF). Furthermore, several safety and tolerability measures were obtained. After six weeks, both groups showed significant reductions of positive and negative symptoms. In addition, affective state, psychosocial functioning and clozapine side effects improved without significant differences between the groups. Both approaches were well tolerated. However, the ziprasidone group experienced a small elongation of the QTc interval and a reduction of extrapyramidal symptoms. Patients under clozapine-risperidone therapy developed a rise of serum prolactin levels. The clozapine augmentation with ziprasidone or risperidone resulted in significant psychopathological improvements. The side effects differed between the treatment groups. Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary. This study evaluated the efficacy and safety of risperidone monotherapy in the treatment of acute bipolar mania.
                Patients with DSM-IV bipolar I disorder experiencing an acute manic episode (baseline Young Mania Rating Scale score >/==" BORDER="0">20) were randomly assigned to 3 weeks of treatment with risperidone (flexible dose: 1-6 mg/day) or placebo. The primary efficacy measure was the mean baseline-to-endpoint change in total score on the Young Mania Rating Scale. Secondary efficacy measures included the Clinical Global Impression (CGI) severity rating and scores on the Montgomery-Asberg Depression Rating Scale, Positive and Negative Syndrome Scale, and Global Assessment Scale (GAS). Safety assessments consisted of monitoring adverse events, vital signs, electrocardiogram and laboratory results, and scores on the Extrapyramidal Symptom Rating Scale.
                Subjects (N=259) received treatment with either risperidone (N=134) or placebo (N=125). The mean modal dose of risperidone was 4.1 mg/day. Improvement in mean Young Mania Rating Scale total score (adjusted for covariates) was significantly greater in the risperidone than in the placebo group at endpoint (mean change=-10.6 [SD=9.5] versus -4.8 [SD=9.5], respectively), with significant between-group differences seen as early as 3 days after start of treatment (change with risperidone: mean=-6.8 [SD=5.8]; change with placebo: mean=-4.0 [SD=5.8]) and continuing throughout all time points. Improvements in CGI severity ratings and scores on the Montgomery-Asberg Depression Rating Scale, Positive and Negative Syndrome Scale, and GAS were also significantly greater among patients receiving risperidone than those given placebo. The most common adverse event reported among risperidone patients was somnolence. While Extrapyramidal Symptom Rating Scale scores were significantly greater in patients receiving risperidone, mean total and subscale scores were low.
                Risperidone monotherapy was significantly more efficacious than placebo in the treatment of acute mania and demonstrated a rapid onset of action. Risperidone was well tolerated by patients in this study. The atypical antipsychotics, amisulpride and risperidone, have different receptor affinity characteristics. Although the relative efficacy of both drugs compared to conventional antipsychotics is well established, it remains unclear how the efficacy of amisulpride compares with risperidone. There have been no controlled studies comparing amisulpride to risperidone in Asian patients. The purpose of this study was to compare the efficacy and safety of amisulpride with that of risperidone in Taiwanese schizophrenic patients.
                Patients with productive positive symptoms (n = 48) were enrolled into this double-blind, randomized pilot study for 6 weeks. Patients received either amisulpride (400-800 mg/day) or risperidone (4-8 mg/day). Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI), Social and Occupational Functioning Assessment Scale (SOFAS), and patients' subjective responses to treatment were assessed during the trial period. Adverse events were recorded at each follow-up visit.
                At the end of the trial, the mean dosage was 630 +/- 134 mg/day and 6.88 +/- 1.54 mg/day for amisulpride and risperidone, respectively. There was no significant difference in the reduction of the PANSS total score (amisulpride -24.1 versus risperidone -28.4, p = 0.999), the PANSS positive subscale score (amisulpride -6.8 versus risperidone -8.3, p = 0.467), the PANSS negative subscale score (amisulpride -5.6 versus risperidone -6.4, p = 0.999), or the CGI score between the two groups. The extrapyramidal symptom ratings, the improvement in the SOFAS (amisulpride 11.1 versus risperidone 10.0) and the subjective response (amisulpride 82% versus risperidone 83%) were comparable. No serious adverse events were recorded in either treatment group. There was a statistically significant body weight gain in the risperidone group. In contrast, there was a statistically, though not clinically, significant reduction of blood pressure and heart rate in the amisulpride group.
                This study suggests that amisulpride is as effective as risperidone in the treatment of patients with schizophrenia. Both drugs were well tolerated, but had different side effect profiles. Olanzapine and risperidone, both second-generation antipsychotic agents, represent two different pharmacologic strategies. Although they share some in vitro properties, they differ by virtue of their chemical structure, spectrum of receptor binding affinities, animal neuropharmacology, pharmacokinetics, and in vivo neuroimaging profile. Based on such differences, it was hypothesized that the two compounds would show distinct safety and/or efficacy characteristics. To test this hypothesis, an international, multicenter, double-blind, parallel-group, 28-week prospective study was conducted with 339 patients who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms. However, olanzapine demonstrated significantly greater efficacy in negative symptoms (Scale for Assessment of Negative Symptoms summary score), as well as overall response rate (> or = 40% decrease in the Positive and Negative Syndrome Scale total score). Furthermore, a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves. The incidence of extrapyramidal side effects, hyperprolactinemia, and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients. In addition, statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts. Thus, the differential preclinical profiles of these two drugs were also evident in a controlled, clinical investigation. Olanzapine seemed to have a risk-versus-benefit advantage. Atypical antipsychotic drugs produce improvement in some domains of cognition as well as psychopathology in patients with schizophrenia. However, the effect of combinations of atypical antipsychotic drugs on cognitive function is unknown. The aim of this study was to compare the effect of risperidone or placebo on cognitive function in patients with schizophrenia who were previously treated with clozapine monotherapy.
                This prospective, randomized, double-blind, placebo-controlled, 6-week study included 30 patients with DSM-IV schizophrenia. Patients whose psychopathology was no more than partially responsive to clozapine treatment were randomly assigned to receive adjunctive treatment with risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Cognitive test scores for verbal learning and memory, verbal fluency, attention, executive function, verbal working memory, and motor function were the primary outcome measures. Secondary outcome measures included assessment of psychopathology, extrapyramidal side effects, and global functioning. Data were collected between November 2001 and July 2003.
                Significant improvement was found in both treatment groups in a variety of cognitive measures, but there was significantly greater improvement in the placebo-augmented group on measures of initial learning acquisition and attention. The improvement in cognition was not correlated with improvement in psychopathology. There were significant correlations between improvement in verbal working memory, verbal learning and memory, and attention and quality of life and global functioning in the placebo-augmented but not the risperidone-augmented group.
                Adjunctive treatment with risperidone for 6 weeks in patients with schizophrenia who had received chronic treatment with clozapine does not significantly improve cognitive function. Sertindole is a non-sedating atypical antipsychotic effective in the management of schizophrenia and is associated with placebo-level incidence of extrapyramidal symptoms (EPS). In this randomized, double-blind, parallel-group, flexible-dose, multi-centre study, the efficacy and tolerability of sertindole was directly compared with another atypical antipsychotic in patients with schizophrenia. A total of 187 patients were randomly assigned to treatment with sertindole (12-24 mg/day, n=98) or risperidone (4-10 mg/day, n=89) for 12 weeks. Although early termination reduced the power of the study, some significant between-group differences were evident. Sertindole reduced the mean Positive and Negative Syndrome Scale total scores to a greater extent than risperidone, and the difference reached statistical significance at endpoint for the Observed Cases (OC) dataset. Moreover, sertindole was superior for the treatment of negative symptoms compared to risperidone (P<0.05, Last Observation Carried Forward and OC). Both treatment groups were similarly effective in improving Clinical Global Impression (Severity and Improvement), the Drug Attitude Inventory and Global Assessment of Functioning scores. Sertindole and risperidone were both well tolerated. Numerically, fewer patients in the sertindole group (19%) reported EPS-related adverse events than in the risperidone group (28%), although significantly more sertindole-treated patients reported QT prolongation and abnormal ejaculation volume (P<0.05). In conclusion, sertindole was well tolerated and demonstrated clinically relevant efficacy advantages over risperidone. 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. This study presents a meta-analysis of the influence of several potentially biasing factors (eg industry support, extrapyramidal side effects) on efficacy of studies comparing second-generation antipsychotic (SGA) with first-generation antipsychotic (FGA) medications. We used the dataset from our previously published meta-analysis of 124 randomized controlled trials (RCTs) comparing SGAs with FGAs, to evaluate whether certain possible biases could influence the actual outcome on the total score of the Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impressions (CGI) scores. Industry sponsorship was determined by contact with authors or publication statement. We calculated whether (1) industry sponsorship, (2) study quality, (3) extrapyramidal symptoms (EPS) properties, or (4) prophylactic antiparkinsonian medications influenced SGA vs FGA efficacy for each drug and averaged overall by two Hedges and Olkin-based meta-analyses. The analysis found that none of the factors was significantly associated with a particular outcome. While industry-sponsored articles may conclude their medication to be more favorable than that of a competitor in an RCT, we found that the observed efficacy was not influenced by sponsorship. Many attribute the finding that SGAs appears to be more efficacious than FGAs to be a result of EPS-decreasing efficacy (or its measurement). We were unable to confirm that the drug's EPS properties or antiparkinsonian management altered actual efficacy. The purpose of this study was to compare the short-term efficacy and safety of risperidone and clozapine in treatment-resistant chronic schizophrenic patients.
                In a controlled double-blind, multicenter study, 86 inpatients with chronic schizophrenia (DSM-III-R), who were resistant to or intolerant of conventional neuroleptics, were randomly assigned to receive risperidone or clozapine for 8 weeks after a 7-day washout period. After a 1-week dose-titration phase, doses were fixed at 6 mg/day of risperidone and 300 mg/day of clozapine for 1 week and then adjusted according to each patient's response. The final mean doses were 6.4 mg/day of risperidone and 291.2 mg/day of clozapine. Treatment efficacy and safety were evaluated with several well-known rating scales.
                Both risperidone and clozapine significantly reduced the severity of psychotic symptoms (scores on the Positive and Negative Syndrome Scale and the Clinical Global Impression scale) from baseline, with no significant between-group differences. At endpoint, 67% of the risperidone group and 65% of the clozapine group were clinically improved (reduction of 20% or more in total Positive and Negative Syndrome Scale score). Risperidone appeared to have a faster onset of action. In both groups extrapyramidal symptoms and other adverse events were few, and their severity was generally mild. Neither group showed evidence of a relation between drug plasma concentrations and clinical effectiveness.
                Risperidone was well tolerated and as effective as medium doses of clozapine in patients with chronic schizophrenia who had been resistant to or intolerant of conventional neuroleptics. This pilot study was undertaken to estimate the acute antipsychotic effect size and side effect propensity of risperidone and olanzapine in the pediatric population, in comparison to haloperidol, a conventional antipsychotic with established efficacy. Risperidone and olanzapine are widely used as first-line treatments to ameliorate psychotic symptoms in youth, but their abilities to specifically treat children and adolescents presenting due to psychotic symptoms have not been rigorously studied. Subjects, selected because of prominent positive psychotic symptoms, were randomly assigned to double-blind, parallel treatment with risperidone, olanzapine, or haloperidol for 8 weeks. The primary outcome was reduction in the Brief Psychiatric Rating Scale for Children total score from baseline to termination. An exploratory, descriptive analysis was done to compare the three treatments. A total of 50 patients, 8-19 years, participated. All treatments reduced symptoms significantly with p-values (corrected for multiple comparisons) of 0.0018 for each of the atypical agents and 0.012 for haloperidol. In all, 88% of subjects treated with olanzapine, 74% treated with risperidone, and 53% treated with haloperidol met response criteria. The primary side effects observed in all patients were mild to moderate sedation, extrapyramidal symptoms, and weight gain. Risperidone and olanzapine acutely reduced psychotic symptoms in this pediatric sample. Exploratory comparisons indicate the magnitude of the antipsychotic response with these atypical agents is comparable to that observed with haloperidol. However, youth treated with risperidone and olanzapine experienced weight gain and extrapyramidal effects that appear more prevalent and severe than reported in adults.
Risperidone seems to produce somewhat more extrapyramidal side effects and clearly more prolactin increase than most other SGAs. It may also differ from other compounds in efficacy and in the occurrence of other adverse effects such as weight gain, metabolic problems, cardiac effects, sedation and seizures. Nevertheless, the large proportion of participants leaving studies early and incomplete reporting of outcomes makes it difficult to draw firm conclusions. Further large trials, especially comparing risperidone with those other new drugs for which only a few RCTs are available, are needed.