Efficacy, safety and tolerability of two dosing regimens in adolescent schizophrenia: double-blind study.

BACKGROUND: Effective treatments for adolescent schizophrenia are needed. AIMS: To compare efficacy and safety of two dosing regimens of risperidone. METHOD: Double-blind, 8-week study. Patients, 13-17 years, with an acute episode of schizophrenia, randomised 1:1 to risperidone 1.5-6.0 mg/day (regimen A; n=125) or 0.15-0.6 mg/day (regimen B; n=132). TRIAL REGISTRATION NUMBER: NCT00034749. RESULTS: Mean total Positive and Negative Syndrome Scale (PANSS) score improved significantly (P<0.001; effect size=0.49) from baseline to end-point for regimen A (mean=96.4 (s.d.=15.39) to mean=72.8 (s.d.=22.52)) compared with regimen B (mean=93.3 (s.d.=14.14) to mean=80.8 (s.d.=24.33)). Treatment-emergent adverse events occurred in 74% (regimen A) and 65% (regimen B) of patients; 4% of patients overall discontinued for adverse events. Mean change in body weight was 3.2 kg (s.d.=3.49) for regimen A and 1.7 kg (s.d.=3.29) for regimen B. CONCLUSIONS: Adolescent patients in the regimen A group showed greater improvement in total PANSS compared with the regimen B group. Treatment was well tolerated.

Risperidone for the treatment of acute mania in children and adolescents with bipolar disorder: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: To evaluate the efficacy, safety, and tolerability of risperidone monotherapy for the treatment of an acute mixed or manic episode in children and adolescents with bipolar I disorder. METHODS: This randomized, placebo-controlled, double-blind, 3-arm study (N = 169) included children and adolescents (ages 10-17 years) with a DSM-IV diagnosis of bipolar I disorder, experiencing a manic or mixed episode. Study participants were randomized to placebo (n = 58), risperidone 0.5-2.5 mg/day (n = 50), or risperidone 3-6 mg/day (n = 61) for 3 weeks. The primary efficacy measure was change in Young Mania Rating Scale (YMRS) total score from baseline to end point. Safety assessments included adverse event (AE) monitoring and scores on extrapyramidal symptom rating scales. RESULTS: Improvement in mean YMRS total score was significantly greater in risperidone-treated subjects than in placebo-treated subjects [mean change (SD) -9.1 (11.0) for placebo; -18.5 (9.7) for risperidone 0.5-2.5 mg (p < 0.001); -16.5 (10.3) for risperidone 3-6 mg (p < 0.001)]. The most common risperidone-associated AEs were somnolence, headache, and fatigue. Mean (SD) weight gain was 0.7 (1.9) kg, 1.9 (1.7) kg, and 1.4 (2.4) kg in the placebo, risperidone 0.5-2.5 mg, and risperidone 3-6 mg groups, respectively, during this 3-week study. CONCLUSIONS: At daily doses of 0.5-2.5 mg and 3-6 mg, risperidone was effective and well tolerated in children and adolescents experiencing acute manic or mixed episodes of bipolar I disorder. Results indicate that risperidone 0.5-2.5 mg has a better benefit-risk profile than risperidone 3-6 mg.

A randomized, double-blind, placebo-controlled study of risperidone maintenance treatment in children and adolescents with disruptive behavior disorders.

OBJECTIVE: The authors compared the effects of maintenance versus withdrawal of risperidone treatment in children and adolescents with symptoms of disruptive behavior disorder. METHOD: Patients with disruptive behavior disorder (5-17 years of age and a range of intellect) who had responded to risperidone treatment over 12 weeks were randomly assigned to 6 months of double-blind treatment with either risperidone or placebo. The primary efficacy measure was time to symptom recurrence, defined as sustained deterioration on either the Clinical Global Impression severity rating (/2 points) or the conduct problem subscale of the Nisonger Child Behavior Rating Form (/7 points). Secondary efficacy measures included rates of discontinuation due to symptom recurrence, disruptive behavior disorder symptoms, and general function. Safety and tolerability were also assessed. Risperidone dosage was based on weight (patients <50 kg: 0.25-0.75 mg/day; patients /50 kg: 0.5-1.5 mg/day). RESULTS: Treatment was initiated in 527 patients, with 335 randomly assigned to a double-blind maintenance condition. Time to symptom recurrence was significantly longer in patients who continued risperidone treatment than in those switched to placebo. Symptom recurrence in 25% of patients occurred after 119 days with risperidone and 37 days with placebo. Secondary efficacy measures also favored risperidone over placebo. Weight increased over the initial 12 weeks of treatment (mean weight z score change=0.2, SD=2.7, N=511), after which it plateaued. CONCLUSIONS: This study is the first placebo-controlled maintenance versus withdrawal trial of its kind in disruptive behavior disorder and provides evidence that patients who respond to initial treatment with risperidone would benefit from continuous treatment over the longer term.

Long-term use of risperidone in children with disruptive behavior disorders and subaverage intelligence: efficacy, safety, and tolerability.

OBJECTIVE: The aim of this study was to assess the long-term efficacy and tolerability of risperidone in the treatment of children and adolescents with disruptive behavior disorder (DBD) and below-average intelligence (IQ < 84) over a cumulative period of 2 years. METHODS: We followed 48 patients (6-15 years of age), who had previously completed a 1- year open-label study of risperidone, for an additional year of treatment. Efficacy was assessed using the conduct problem subscale of the Nisonger Child Behavior Rating Form (N-CBRF) as a primary outcome measure; other N-CBRF subscales, the Aberrant Behavior Checklist (ABC), and the Clinical Global Impression (CGI) of severity were secondary efficacy measures. Safety and tolerability were also assessed. RESULTS: Of the 48 patients enrolled in this extension study, 33 (69%) completed the trial. The efficacy benefits from the original study were maintained over the course of the extension study. Safety and tolerability were good overall, with the number of adverse events (AEs) decreasing in the extension trial, compared to the original trial. Six patients (13%) discontinued owing to AEs. Weight gain observed in the original trial stabilized during this extension trial. Cognitive testing demonstrated small, but significant, improvements in cognitive ability. CONCLUSIONS: Risperidone is safe and effective in treating DBDs in children over a cumulative period of 2 years.

Comparative efficacy and safety of long-acting risperidone and risperidone oral tablets.

A double-blind study of long-acting injectable risperidone and oral risperidone tablets was conducted in 640 patients with schizophrenia. All patients received flexible doses of 1-6 mg of oral risperidone for 8 weeks. Doses were stable during weeks 5-8. At the end of week 8, symptomatically stable patients were randomly assigned to receive long-acting risperidone (active injections, dummy oral) or continued oral risperidone (dummy injections, active oral) for 12 weeks. Significant improvements were demonstrated from baseline to endpoint in Positive and Negative Syndrome Scale (PANSS) total (P<0.001) and factor scores (P<0.05) in both groups. According to a noninferiority analysis, the two treatments showed comparable efficacy in total PANSS scores over the short-term. No unexpected adverse events were recorded. The findings indicate that symptomatically stable patients can be safely switched from oral risperidone to long-acting injectable risperidone without compromising efficacy.

Long-term safety and efficacy of risperidone in children with disruptive behaviour disorders. Results of a 2-year extension study.

OBJECTIVE: The aim of this study was to assess the longterm efficacy, safety, and tolerability of risperidone, over a cumulative period of 3 years, in treating children with disruptive behaviour disorders and below average intelligence (IQ 35-84). METHOD: This trial included 35 children (aged 6-16 years), diagnosed with disruptive behaviour disorder. All subjects had previously completed a 1-year, open-label risperidone study, and this extension study followed them for an additional 2 years of treatment. Safety was assessed using the Extrapyramidal Symptom Rating Scale (ESRS), clinical laboratory tests, electrocardiograms, and the recording of adverse events, vital signs, Tanner score, and changes in body mass index (BMI). Efficacy was measured using the Clinical Global Impression of Severity (CGI-S) scale. RESULTS: The beneficial effects observed in the original trial were maintained during the extension. Few extrapyramidal side-effects occurred, as assessed by the ESRS, and there were no cases of tardive dyskinesia. The children showed a modest increase in BMI, part of which may be attributed to normal growth over the 2-year period. Most adverse events were mild or moderate in severity, and none of them were considered probably or very likely related to risperidone. CONCLUSION: Continuing low-dose risperidone for up to 3 years appears to be safe and effective in children with disruptive behaviour disorders.

Mood stabilisers plus risperidone or placebo in the treatment of acute mania. International, double-blind, randomised controlled trial.

BACKGROUND: Few double-blind trials have examined the efficacy of a combination of a mood stabiliser and an atypical antipsychotic in acute mania. AIMS: To determine the efficacy of risperidone in combination with a mood stabiliser in acute mania. METHOD: Patients taking a mood stabiliser were randomised to 3 weeks' treatment with risperidone (n=75) or placebo (n=76). RESULTS: Young Mania Rating Scale (YMRS) scores improved rapidly with significantly greater reductions at week 1 in the risperidone group compared with the placebo group. At end-point YMRS scores decreased by 14.5 and 10.3 points in the risperidone and placebo groups, respectively. Significant improvements v. placebo (P<0.05) were noted in the risperidone group on several other clinically meaningful measures. Additionally, a post hoc analysis excluding carbamazepine-treated patients (plasma concentrations of risperidone active moiety were 40% lower in this group) revealed significantly greater reductions (P=0.047) in YMRS scores in the risperidone group than in the placebo group. Incidence of adverse events was similar in both groups. CONCLUSIONS: Risperidone is superior to placebo when used in combination with lithium or divalproex in acute mania.