Risperidone in children with autism and serious behavioral problems. A double-blind pilot study of risperidone in the treatment of conduct disorder. A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders. Efficacy of risperidone augmentation to antidepressants in the management of suicidality in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. Olanzapine vs risperidone in the management of schizophrenia: a randomized double-blind trial in Australia and New Zealand. Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Adjunctive risperidone treatment in post-traumatic stress disorder: a preliminary controlled trial of effects on comorbid psychotic symptoms. Group cognitive behavior therapy for children with high-functioning autism spectrum disorders and anxiety: a randomized trial. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety. Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomised controlled clinical trial.
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 To examine whether risperidone is superior to placebo in the treatment of youths with conduct disorder.
                This was a 10-week, randomized, double-blind, placebo-controlled study with 2 parallel arms. Ten youths were randomly assigned to receive placebo and 10 youths were randomly assigned to receive risperidone. Patients were seen weekly throughout the trial. Medications could be increased at weekly intervals during the first 6 weeks of the study from an initial dose of 0.25 mg or 0.50 mg each morning, depending on patient weight. Patients weighing less than 50 kg had a maximum total daily dose of risperidone of 1.5 mg. Patients weighing 50 kg or greater had a maximum total daily dose of risperidone of 3.0 mg. The primary outcome measure was the Rating of Aggression Against People and/or Property Scale.
                Risperidone was superior to placebo in ameliorating aggression on most measures. Risperidone was reasonably well tolerated, with none of the risperidone-treated patients developing extrapyramidal side effects.
                These data provide preliminary evidence that risperidone may have efficacy in the treatment of youths with conduct disorder. Because of the small sample size and the brief length of this study, further research is necessary to confirm these findings. Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism. Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism.
                Thirty-one adults (age [mean+/-SD], 28.1+/-7.3 years) with autistic disorder (n=17) or pervasive developmental disorder not otherwise specified (n=14) participated in a 12-week double-blind, placebo-controlled trial of risperidone. Patients treated with placebo subsequently received a 12-week open-label trial of risperidone.
                For persons completing the study, 8 (57%) of 14 patients treated with risperidone were categorized as responders (daily dose [mean+/-SD], 2.9+/-1.4 mg) compared with none of 16 in the placebo group (P<.002). Risperidone was superior to placebo in reducing repetitive behavior (P<.001), aggression (P<.001), anxiety or nervousness (P<.02), depression (P<.03), irritability (P<.01), and the overall behavioral symptoms of autism (P<.02). Objective, measurable change in social behavior and language did not occur. Nine (60%) of 15 patients who received treatment with open-label risperidone following the double-blind placebo phase responded. Other than mild, transient sedation, risperidone was well tolerated, with no evidence of extrapyramidal effects, cardiac events, or seizures.
                Risperidone is more effective than placebo in the short-term treatment of symptoms of autism in adults. Major depressive disorder (MDD) is a severe mental illness with high risk of suicidality. Antidepressant treatment alone is not sufficient for the acute management of risk-taking symptoms of depression. This pilot study was designed to investigate the efficacy of risperidone augmentation to antidepressants in the acute management of suicidality and other core symptoms in MDD with suicidality.
                Twenty-four adult men and women diagnosed with MDD (DSM-IV), having a depressive episode with suicidality despite taking an antidepressant, were enrolled in an 8-week double-blind, placebo-controlled study. Subjects were randomly assigned to receive risperidone (0.25-2 mg/day) or placebo while continuing on their antidepressant therapy. Clinical efficacy in suicidality, depressive symptoms, and impulsivity were assessed after treatment with study drugs for 4 days, weekly for 4 weeks, then every other week for 4 weeks. Adverse events were also recorded at each visit. The study was conducted from June 2004 to April 2007.
                Risperidone significantly reduced suicidal ideations in MDD patients, and the overall effect of risperidone appeared to be superior to placebo. The effect of risperidone was rapid, with onset at 2 weeks' treatment, and was sustained along the course of 8 weeks' treatment. Furthermore, risperidone demonstrated superiority to placebo in improving other symptoms related to suicidality and having better trial completion rate, and the low dose risperidone was well tolerated by subjects in this study.
                Data from this pilot study suggest that risperidone is beneficial as an augmenting treatment in MDD patients who have developed high-risk suicidal ideation during a depressive episode. The antisuicidality effect of risperidone is especially valuable in the acute management of severe depressive symptoms. Although the pilot study is limited by small sample size, the promising results warrant further larger scale investigation in the efficacy of atypical antipsychotics in the treatment of severe depression with suicidality.
                clinicaltrials.gov Identifier: NCT00167154. Improved drug therapy for schizophrenia may represent the best strategy for reducing the costs of schizophrenia and the recurrent chronic course of the disease. Olanzapine and risperidone are atypical antipsychotic agents developed to meet this need. We report a multicenter, double-blind, parallel, 30-week study designed to compare the efficacy, safety, and associated resource use for olanzapine and risperidone in Australia and New Zealand. The study sample consisted of 65 patients who met DSM-IV criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder. Olanzapine-treated patients showed a significantly greater reduction in Positive and Negative Syndrome Scale (PANSS) total, Brief Psychiatric Rating Scale (BPRS) total, and PANSS General Psychopathology scores at endpoint compared to the risperidone-treated patients. Response rates through 30 weeks showed a significantly greater proportion of olanzapine-treated patients had achieved a 20% or greater improvement in their PANSS total score compared to risperidone-treated patients. Olanzapine and risperidone were equivalent in their improvement of PANSS positive and negative scores and Clinical Global Impression-Severity of Illness scale (CGI-S) at endpoint. Using generic and disease-specific measures of quality of life, olanzapine-treated patients showed significant within-group improvement in most measures, and significant differences were observed in favor of olanzapine over risperidone in Quality of Life Scale (QLS) Intrapsychic Foundation and Medical Outcomes Study Short Form 36-item instrument (SF-36) Role Functioning Limitations-Emotional subscale scores. Despite the relatively small sample size, our study suggests that olanzapine has a superior risk:benefit profile compared to risperidone. The authors assessed the efficacy and safety of the first long-acting atypical antipsychotic (long-acting injectable risperidone) in patients with schizophrenia.
                In a 12-week, multicenter, double-blind, randomized study, patients received intramuscular injections every 2 weeks of placebo or long-acting risperidone (25 mg, 50 mg, or 75 mg). The primary measure of efficacy was the change in total score on the Positive and Negative Syndrome Scale.
                Of the 554 patients who were enrolled, 400 entered the double-blind study, and 370 received at least one postbaseline assessment. Mean changes in score of -6.2, -8.5, and -7.4 on the Positive and Negative Syndrome Scale were seen at endpoint for the 25-, 50-, and 75-mg risperidone groups, respectively; all three change scores were significantly different from that seen with placebo (+2.6). Improvements in positive and negative symptoms were also significantly greater in patients receiving risperidone. Long-acting risperidone was well tolerated. Adverse events related to extrapyramidal symptoms were spontaneously reported by 13% of patients receiving placebo and 10% of patients in the 25-mg risperidone group, with higher rates in the 50-mg and 75-mg groups. Severity of extrapyramidal symptoms was mild at baseline and throughout the trial in each treatment group. Mean weight changes were small in the 25-, 50-, and 75-mg risperidone groups (0.5 kg, 1.2 kg, and 1.9 kg, respectively). Injection site pain was rated as low by the patients, consistent with the investigators' pain ratings.
                Long-acting injectable risperidone was efficacious and well tolerated and provides both clinicians and patients with a new mode of treatment that can improve the outcome of long-term therapy. Positive and negative symptoms of psychosis may be common in patients with chronic post-traumatic stress disorder (PTSD), but few studies have investigated the use of antipsychotic agents in these patients. This preliminary study examined the potential efficacy of risperidone in treating psychotic symptoms associated with chronic PTSD. In a 5-week, prospective, randomized, double-blind, placebo-controlled trial, adjunctive risperidone treatment was assessed in 40 combat veterans with chronic PTSD and comorbid psychotic features. Most patients were receiving antidepressants and some other psychotics with doses of concurrent medications held constant for at least 1 month prior to and during the study. Thirty-seven patients completed at least 1 week of treatment with risperidone or placebo. The Positive and Negative Syndrome Scale (PANSS) and the Clinician Administered PTSD Scale (CAPS) were used to assess symptoms. The PANSS was the primary outcome measure. At treatment endpoint, risperidone-treated patients showed a significantly greater decrease from baseline, albeit modest, in psychotic symptoms (PANSS total scores) than placebo-treated patients (P < 0.05). CAPS ratings declined significantly in both groups but did not differ significantly between groups. However, CAPS re-experiencing subscale scores had greater improvement in the risperidone-treated patients at week 5 (P < 0.05, completer analysis) with a trend towards greater improvement versus placebo a endpoint (P < 0.1, LOCF). Risperidone was well tolerated with minimal extrapyramidal symptoms. These preliminary results support studying the potential efficacy of risperidone for treating global psychotic symptoms associated with chronic PTSD with a suggestion that core re-experiencing symptoms may also be responsive. Further research using randomized, controlled trial designs in larger patient groups are needed to define more adequately the role of risperidone and other atypical agents in PTSD. Children with high-functioning autism spectrum disorders (ASD) are at high risk for developing significant anxiety. Anxiety can adversely impact functioning across school, home and community environments. Cognitive behavioral therapies (CBT) are frequently used with success for children with anxiety symptoms. Modified CBT interventions for anxiety in children with ASD have also yielded promising results.
                Fifty children with high-functioning ASD and anxiety were randomizedto group CBT or treatment-as-usual (TAU) for 12 weeks. Independent clinical evaluators, blind to condition, completed structured interviews (Anxiety Disorders Interview Schedule – Parent Version;ADIS-P) pre- and post-intervention condition.
                Forty-seven children completed either the CBT or TAU condition. Results indicated markedly better outcomes for the CBT group. Significant differences by group were noted in Clinician Severity Ratings, diagnostic status, and clinician ratings of global improvement. In the intent-to-treat sample, 10 of 20 children (50%) in the CBT group had a clinically meaningful positive treatment response, compared to 2 of 23 children (8.7%) in the TAU group.
                Initial results from this randomized, designed treatment study suggest that agroup CBT intervention specifically developed for children with ASD may be effective in decreasing anxiety. Limitations of this study include small sample size, lack of an attention control group, and use of outcome measures normed with typically developing children Prevention of relapse is a major goal of maintenance treatment in patients with psychotic disorders. We performed a long-term comparison of a newer, atypical antipsychotic drug, risperidone, and an older, conventional neuroleptic drug, haloperidol, in terms of the rate of relapse in patients with schizophrenia and schizoaffective disorder.
                In a double-blind, prospective study at 40 sites, we randomly assigned adult outpatients in stable condition with chronic schizophrenia or schizoaffective disorder to receive treatment with flexible doses of either risperidone or haloperidol for a minimum of one year.
                Of the 397 patients who underwent randomization, data from 2 were excluded because they did not receive study medication; data from all 30 patients from one site were excluded by the sponsor, the Janssen Research Foundation, because of concern about the integrity of the data. The median duration of treatment was 364 days in the risperidone group and 238 days in the haloperidol group (P=0.02). Of the 177 patients assigned to risperidone and the 188 assigned to haloperidol who remained in the analysis, 44.1 percent and 52.7 percent, respectively, discontinued treatment for reasons other than relapse. The Kaplan-Meier estimate of the risk of relapse at the end of the study was 34 percent for the risperidone group and 60 percent for the haloperidol group (P<0.001); the risk ratio for relapse with haloperidol, from the Cox model, was 1.93 (95 percent confidence interval, 1.33 to 2.80; P<0.001). Early discontinuation of treatment for any reason was more frequent among haloperidol-treated patients (risk ratio, 1.52; 95 percent confidence interval, 1.18 to 1.96). Patients in the risperidone group had greater reductions in the mean severity of both psychotic symptoms and extrapyramidal side effects than those in the haloperidol group.
                Adult outpatients with clinically stable schizophrenia or schizoaffective disorder have a lower risk of relapse if they are treated with risperidone than if they are treated with haloperidol. 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. 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.
Risperidone can be beneficial in some features of autism. However there are limited data available from studies with small sample sizes. In addition, there lacks a single standardised outcome measure allowing adequate comparison of studies, and long-term followup is also lacking. Further research is necessary to determine the efficacy pf risperidone in clinical practice.