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

Johnson & Johnson Pharmaceutical Research & Development, Beerse, Belgium.
Bipolar Disorders (Impact Factor: 4.97). 11/2009; 11(7):687-700. DOI: 10.1111/j.1399-5618.2009.00750.x
Source: PubMed


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.
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.
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.
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.

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    • "Approval for treatment of bipolar disorder came from efficacy demonstrated in a 3-week, randomized, double-blind, placebo-controlled, multicenter trial of patients ranging in ages from 10 to 17 years (n=169).25 The efficacy on the primary parameter in those taking 3–6 mg/day (n=61) was comparable to those taking 0.5–2.5 mg/day (n=50). "
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    ABSTRACT: Objective To review the metabolic consequences of second-generation antipsychotics in youth and current monitoring and intervention guidelines for optimal treatment. Background Second-generation antipsychotics have largely replaced the use of first-generation antipsychotics in treating psychotic disorders in youth. In addition, there has been a dramatic increase in using these medications to treat a variety of nonpsychotic disorders. These medications have significant metabolic side effects, including weight gain. This raises concern, given the problem of pediatric obesity. Materials and methods A review of current literature looking at prescribing practices and possible reasons for the increased use of second-generation antipsychotics in children and adolescents was conducted. Review of the mechanisms for why youth may be particularly vulnerable to the metabolic consequences (particularly weight gain) was similarly completed. In addition, data supporting the efficacy, rationale, and unique side-effect profile of each individual second-generation drug were evaluated to help inform providers on when and what to prescribe, along with current monitoring practices. The current evidence base for possible interventions regarding the management of antipsychotic-induced weight gain was also evaluated. Results and conclusion On the basis of the literature review, there are several speculated reasons for the increase in prescriptions of second-generation antipsychotics. The choice of antipsychotic for youth should be based upon the disorder being treated along with the unique side-effect profile for the most commonly used second-generation antipsychotics. Monitoring strategies are also individualized to each antipsychotic. The current interventions recommended for antipsychotic-induced weight gain include lifestyle management, switching medication to a drug with a lower propensity for weight gain, and pharmacologic (particularly metformin) treatment.
    Full-text · Article · Sep 2014 · Adolescent Health, Medicine and Therapeutics
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    • "Furthermore, treatment adherence is often challenging to capture accurately in naturalistic long-term studies such as the one reported here. This is particularly important since several antipsychotic-related adverse events that could potentially reduce adherence, such as sedation or hyperprolactinemia, are dose-dependent [36,39,40]. Finally, adjusting the dose for weight, as we have done, or measuring the medication serum concentration could increase the sensitivity of dose as a predictor of weight gain. "
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    ABSTRACT: BACKGROUND: Most clinical trials of antipsychotics in children are brief, failing to address their long-term safety, particularly when taken concurrently with other psychotropics. This hypothesis-generating analysis evaluates potential correlates of weight gain in children receiving extended risperidone treatment. METHODS: Medically healthy 7-17 year-old patients treated with risperidone for six months or more were enrolled. Anthropometric measurements were conducted. Developmental and medication history was obtained from the medical record. Information related to birth weight, dietary intake, physical activity, and parental weight was collected. Mixed regression analyses explored the contribution of various demographic and clinical factors to age- and sex-adjusted weight and body mass index (BMI) z scores over the treatment period. RESULTS: The sample consisted of 110 patients (89 % males) with a mean age of 11.8 years (sd = 2.9) upon enrollment. The majority had an externalizing disorder and received 0.03 mg/kg/day (sd = 0.02) of risperidone, for 2.5 years (sd = 1.7), to primarily target irritability and aggression (81 %). Polypharmacy was common with 71 % receiving psychostimulants, 50 % selective serotonin reuptake inhibitors (SSRIs), and 32 % alpha2-agonists. Weight and BMI z score were positively correlated with baseline weight at the start of risperidone, treatment duration, and the weight-adjusted dose of risperidone but inversely associated with the weight-adjusted dose of psychostimulants and the concurrent use of SSRIs and alpha2-agonists. The effect of risperidone dose appeared to attenuate as treatment extended while that of psychostimulants became more significant. The rate of change in weight (or BMI) z score prior to and within the first 12 weeks of risperidone treatment did not independently predict future changes neither did birth weight, postnatal growth, dietary intake, physical activity, or parental weight. CONCLUSIONS: This comprehensive analysis exploring correlates of long-term weight (or BMI) change in risperidone-treated youths revealed that pharmacotherapy exerts significant but complex effects. Trial Registration Not applicable.
    Full-text · Article · May 2012 · Child and Adolescent Psychiatry and Mental Health
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    • "There have been few short-duration trials with other antipsychotics. Haas et al. noted that risperidone (0.5–2.5 mg/day) was efficacious and relatively well tolerated in the acute treatment of manic or mixed episodes in children and adolescents in the ages of 10 to 17 years [45]. In another RCT, 161 adolescents with an acute manic or mixed episode, Olanzapine (2.5–20 mg/d) was superior to placebo after 3 weeks [46]. "
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    ABSTRACT: . Despite controversy, bipolar disorder (BD) is being increasingly diagnosed in under 18s. There is scant information regarding its treatment and uncertainty regarding the status of “severe mood dysregulation (SMD)” and how it overlaps with BD. This article collates available research on treatment of BD in under 18s and explores the status of SMD. Methods . Literature on treatment of BD in under 18s and on SMD were identified using major search engines; these were then collated and reviewed. Results . Some markers have been proposed to differentiate BD from disruptive behaviour disorders (DBD) in children. Pharmacotherapy restricted to short-term trials of mood-stabilizers and atypical-antipsychotics show mixed results. Data on maintenance treatment and non-pharmacological interventions are scant. It is unclear whether SMD is an independent disorder or an early manifestation of another disorder. Conclusions . Valproate, lithium, risperidone, olanzapine, aripiprazole and quetiapine remain first line treatments for acute episodes in the under 18s with BD. Their efficacy in maintenance treatment remains unclear. There is no validated treatment for SMD. It is likely that some children who are currently diagnosed with BD and DBD and possibly most children currently diagnosed with SMD will be subsumed under the proposed category in the DSM V of disruptive mood dysregulation disorder with dysphoria.
    Full-text · Article · Jan 2012 · Depression research and treatment
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