quetiapine-fumarate and Attention-Deficit-and-Disruptive-Behavior-Disorders

This is an update of the original Cochrane Review, last published in 2012 (Loy 2012). Children and youths with disruptive behaviour disorders may present to health services, where they may be treated with atypical antipsychotics. There is increasing usage of atypical antipsychotics in the treatment of disruptive behaviour disorders.. To evaluate the effect and safety of atypical antipsychotics, compared to placebo, for treating disruptive behaviour disorders in children and youths. The aim was to evaluate each drug separately rather than the class effect, on the grounds that each atypical antipsychotic has different pharmacologic binding profile (Stahl 2013) and that this is clinically more useful.. In January 2017, we searched CENTRAL, MEDLINE, Embase, five other databases and two trials registers.. Randomised controlled trials of atypical antipsychotics versus placebo in children and youths aged up to and including 18 years, with a diagnosis of disruptive behaviour disorders, including comorbid ADHD. The primary outcomes were aggression, conduct problems and adverse events (i.e. weight gain/changes and metabolic parameters). The secondary outcomes were general functioning, noncompliance, other adverse events, social functioning, family functioning, parent satisfaction and school functioning.. We used standard methodological procedures expected by Cochrane. Two review authors (JL and KS) independently collected, evaluated and extracted data. We used the GRADE approach to assess the quality of the evidence. We performed meta-analyses for each of our primary outcomes, except for metabolic parameters, due to inadequate outcome data.. We included 10 trials (spanning 2000 to 2014), involving a total of 896 children and youths aged five to 18 years. Bar two trials, all came from an outpatient setting. Eight trials assessed risperidone, one assessed quetiapine and one assessed ziprasidone. Nine trials assessed acute efficacy (over four to 10 weeks); one of which combined treatment with stimulant medication and parent training. One trial was a six-month maintenance trial assessing symptom recurrence.The quality of the evidence ranged from low to moderate. Nine studies had some degree of pharmaceutical support/funding. Primary outcomesUsing the mean difference (MD), we combined data from three studies (238 participants) in a meta-analysis of aggression, as assessed using the Aberrant Behaviour Checklist (ABC) ‒ Irritability subscale. We found that youths treated with risperidone show reduced aggression compared to youths treated with placebo (MD -6.49, 95% confidence interval (CI) -8.79 to -4.19; low-quality evidence). Using the standardised mean difference (SMD), we pooled data from two risperidone trials (190 participants), which used different scales: the Overt Aggression Scale ‒ Modified (OAS-M) Scale and the Antisocial Behaviour Scale (ABS); as the ABS had two subscales that could not be combined (reactive and proactive aggression), we performed two separate analyses. When we combined the ABS Reactive subscale and the OAS-M, the SMD was -1.30 in favour of risperidone (95% CI -2.21 to -0.40, moderate-quality evidence). When we combined the ABS Proactive subscale and OAS-M, the SMD was -1.12 (95% CI -2.30 to 0.06, moderate-quality evidence), suggesting uncertainty about the estimate of effect, as the confidence intervals overlapped the null value. In summary, there was some evidence that aggression could be reduced by risperidone. Data were lacking on other atypical antipsychotics, like quetiapine and ziprasidone, with regard to their effects on aggression.We pooled data from two risperidone trials (225 participants) in a meta-analysis of conduct problems, as assessed using the Nisonger Child Behaviour Rating Form ‒ Conduct Problem subscale (NCBRF-CP). This yielded a final mean score that was 8.61 points lower in the risperidone group compared to the placebo group (95% CI -11.49 to -5.74; moderate-quality evidence).We investigated the effect on weight by performing two meta-analyses. We wanted to distinguish between the effects of antipsychotic medication only and the combined effect wit. There is some evidence that in the short term risperidone may reduce aggression and conduct problems in children and youths with disruptive behaviour disorders There is also evidence that this intervention is associated with significant weight gain.For aggression, the difference in scores of 6.49 points on the ABC ‒ Irritability subscale (range 0 to 45) may be clinically significant. It is challenging to interpret the clinical significance of the differential findings on two different ABS subscales as it may be difficult to distinguish between reactive and proactive aggression in clinical practice. For conduct problems, the difference in scores of 8.61 points on the NCBRF-CP (range 0 to 48) is likely to be clinically significant. Weight gain remains a concern.Caution is required in interpreting the results due to the limitations of current evidence and the small number of high-quality trials. There is a lack of evidence to support the use of quetiapine, ziprasidone or any other atypical antipsychotic for disruptive behaviour disorders in children and youths and no evidence for children under five years of age. It is uncertain to what degree the efficacy found in clinical trials will translate into real-life clinical practice. Given the effectiveness of parent-training interventions in the management of these disorders, and the somewhat equivocal evidence on the efficacy of medication, it is important not to use medication alone. This is consistent with current clinical guidelines.

Topics: Adolescent; Aggression; Antipsychotic Agents; Anxiety Disorders; Attention Deficit and Disruptive Behavior Disorders; Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Conduct Disorder; Depressive Disorder, Major; Dibenzothiazepines; Humans; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Thiazoles; Weight Gain

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Attention Deficit and Disruptive Behavior Disorders; Benzodiazepines; Child; Clozapine; Dibenzothiazepines; Drug Interactions; Drug Monitoring; Humans; Olanzapine; Pediatrics; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone

Disruptive behaviour disorders include conduct disorder, oppositional defiant disorder and disruptive behaviour not otherwise specified. Attention deficit hyperactivity disorder (ADHD) is frequently associated with disruptive behaviour disorders. The difficulties associated with disruptive behaviour disorders are demonstrated through aggression and severe behavioural problems. These often result in presentation to psychiatric services and may be treated with medications such as atypical antipsychotics. There is increasing evidence of a significant rise in the use of atypical antipsychotics for treating disruptive behaviour disorders in child and adolescent populations.. To evaluate the effect and safety of atypical antipsychotics, compared to placebo, for treating disruptive behaviour disorders in children and youths. . We searched the following databases in August 2011: CENTRAL (2011, Issue 3), MEDLINE (1948 to August Week 1), EMBASE (1980 to 2011 Week 32), PsycINFO (1806 to August Week 2 2011), CINAHL (1937 to current), ClinicalTrials.gov (searched 15 August 2011), Australian New Zealand Clinical Trials Registry (ANZCTR) (searched 15 August 2011), CenterWatch (searched 15 August 2011) and ICTRP (searched 15 August 2011).. We included randomised controlled trials with children and youths up to and including the age of 18, in any setting, with a diagnosis of a disruptive behaviour disorder. We included trials where participants had a comorbid diagnosis of attention deficit hyperactivity disorder, major depression or an anxiety disorder.. Two review authors independently selected the studies and disagreements were resolved by discussion. Two review authors extracted data independently. One review author entered data into Review Manager software and another checked it. We contacted trial authors for information about adverse effects and to provide missing data.. We included eight randomised controlled trials, spanning 2000 to 2008. Seven assessed risperidone and one assessed quetiapine. Three of the studies were multicentre. Seven trials assessed acute efficacy and one assessed time to symptom recurrence over a six-month maintenance period.We performed meta-analyses for the primary outcomes of aggression, conduct problems and weight changes but these were limited by the available data as different trials reported either mean change scores (average difference) or final/post-intervention raw scores and used different outcome measures. We also evaluated each individual trial's treatment effect size where possible, using Hedges' g.For aggression, we conducted two meta-analyses. The first included three trials (combined n = 238) using mean difference (MD) on the Aberrant Behaviour Checklist (ABC) Irritability subscale. Results yielded a final mean score with treatment that was 6.49 points lower than the post-intervention mean score with placebo (95% confidence interval (CI) -8.79 to -4.19). The second meta-analysis on aggression included two trials (combined n = 57) that employed two different outcome measures (Overt Aggression Scale (modified) (OAS-M) and OAS, respectively) and thus we used a standardised mean difference. Results yielded an effect estimate of -0.18 (95% CI -0.70 to 0.34), which was statistically non-significant.We also performed two meta-analyses for conduct problems. The first included two trials (combined n = 225), both of which employed the Nisonger Child Behaviour Rating Form - Conduct Problem subscale (NCBRF-CP). The results yielded a final mean score with treatment that was 8.61 points lower than that with placebo (95% CI -11.49 to -5.74). The second meta-analysis on conduct problems included two trials (combined n = 36), which used the Conners' Parent Rating Scale - Conduct Problem subscale (CPRS-CP). Results yielded a mean score with treatment of 12.67 lower than with placebo (95% CI -37.45 to 12.11), which was a statistically non-significant result.With respect to the side effect of weight gain, a meta-analysis of two studies (combined n = 138) showed that participants on risperidone gained on average 2.37 kilograms more than those in the placebo group over the treatment period (MD 2.37; 95% CI 0.26 to 4.49).For individual trials, there was a range of effect sizes (ranging from small to large) for risperidone reducing aggression and conduct problems. The precision of the estimate of the effe. There is some limited evidence of efficacy of risperidone reducing aggression and conduct problems in children aged 5 to 18 with disruptive behaviour disorders in the short term.For aggression, the difference in scores of 6.49 points on the ABC Irritability subscale (range 0 to 45) may be clinically significant. For conduct problems, the difference in scores of 8.61 points on the NCBRF-CP (range 0 to 48) is likely to be clinically significant.Caution is required due to the limitations of the evidence and the small number of relevant high-quality studies. The findings from the one study assessing impact in the longer term suggest that the effects are maintained to some extent (small effect size) for up to six months. Inadequately powered studies produced non-significant results. The evidence is restricted by heterogeneity of the population (including below average and borderline IQ), and methodological issues in some studies, such as use of enriched designs and risk of selection bias. No study addressed the issue of pre-existing/concurrent psychosocial interventions, and comorbid stimulant medication and its dosage was only partially addressed. There is currently no evidence to support the use of quetiapine for disruptive behaviour disorders in children and adolescents.It is uncertain to what degree the efficacy found in clinical trials will translate into real life clinical practice. Participants in the studies were recruited from clinical services but those who agree to take part in the clinical trials are a subset of the overall population presenting for care. There are no research data for children under five years of age. Further high-quality research is required with large samples of clinically representative youths and long-term follow-up to replicate current findings.

Topics: Adolescent; Aggression; Antipsychotic Agents; Anxiety Disorders; Attention Deficit and Disruptive Behavior Disorders; Attention Deficit Disorder with Hyperactivity; Conduct Disorder; Depressive Disorder, Major; Dibenzothiazepines; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Weight Gain

The use of second-generation antipsychotics (SGAs) in youth has increased considerably. Increases are mainly attributable to treatment of disruptive behaviour disorders (DBDs). Our objective was to review the evidence regarding the efficacy of SGAs for DBDs in youth.. We performed a systematic review of all randomized controlled trials (RCTs) of SGAs and placebo for the treatment of DBDs in youth, focusing on efficacy data.. Eight RCTs in youth with DBDs were included. Five RCTs evaluated the use of risperidone in youth with the combination of subaverage-borderline IQ and disruptive behaviour-aggression. Single RCTs evaluated the use of risperidone for treatment-resistant aggression in attention-deficit hyperactivity disorder and for the treatment of conduct disorder (CD), and a single RCT evaluated the use of quetiapine for adolescent CD. The efficacy results of each of these studies are described.. Four placebo-controlled studies support the short-term efficacy of low-dose risperidone in youth with a subaverage IQ. Placebo-controlled evidence is weak or nonexistent for SGAs other than risperidone, and is weak in youth with an average IQ. Multiple factors likely account for the disconnect between this limited evidence base and the frequent use of SGAs for DBDs in clinical practice. These include extrapolation from studies in youth with autism or a subaverage IQ to normally developing youth; ease of SGA titration and the mistaken perception that little monitoring is required; unavailability of psychosocial treatments; limited familiarity with other pharmacological options; clinical and cultural norms; and the influence of the pharmaceutical industry.

Topics: Adolescent; Antipsychotic Agents; Attention Deficit and Disruptive Behavior Disorders; Child; Child, Preschool; Dibenzothiazepines; Humans; Intellectual Disability; Quetiapine Fumarate; Risperidone

Diagnosis of bipolar disorder in children and adolescents is increasing, and the early-onset form of bipolar disorder usually carries more morbidity than later-onset forms. Patient education and psychotherapeutic and psychosocial interventions should be used in conjunction with carefully planned medication regimens. Recent data support the use of atypical antipsychotics for manic or mixed states in children and adolescents. However, more information is needed about long-term treatment of mania, treatment of bipolar depression, and treatment of comorbid psychiatric conditions.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Attention Deficit and Disruptive Behavior Disorders; Bipolar Disorder; Child; Comorbidity; Dibenzothiazepines; Disorders of Excessive Somnolence; Humans; Obesity; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Weight Gain

Disruptive behavior disorders, including conduct disorder, oppositional defiant disorder, and disruptive behavior disorder not otherwise specified, are serious conditions in children and adolescents that include a behavior pattern of violating the basic rights of others and age-appropriate rules or standards and may include aggressive behavior. Although no pharmacotherapy is currently approved for use in this population, evidence suggests that atypical antipsychotic treatment may be useful in patients with these conditions who present with problematic aggression. Currently, research on risperidone shows it to be effective in treating aggressive behavior in this patient population. Limited research is also available on olanzapine, quetiapine, and aripiprazole, but more research is needed on these and other agents. As with any pharmacotherapy, adverse events (including weight gain, headache, and somnolence) should be carefully considered with these medications, especially in children and adolescents, and it is important to properly dose and monitor patients during medication therapy.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Attention Deficit and Disruptive Behavior Disorders; Attention Deficit Disorder with Hyperactivity; Benzodiazepines; Child; Dibenzothiazepines; Disorders of Excessive Somnolence; Headache; Humans; Methylphenidate; Obesity; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone

Atypical antipsychotics offer superior safety and similar efficacy compared with conventional agents in adults with psychotic disorders. Consequently, atypical antipsychotics have been increasingly used in children and adolescents. Because most information now available on pediatric use comes from case reports and small open-label studies rather than large controlled trials, treatment in pediatric patients is often guided by experience with adults or based on limited evidence in youths. Although the literature contains reports on the use of each agent in this class in children, risperidone has been the focus of the greatest number of reports. However, the atypical antipsychotics are not interchangeable; each has a unique pharmacologic profile and may differ considerably in terms of adverse effects. Evidence on the use of atypical antipsychotics in children and adolescents is summarized in this review.

Topics: Adolescent; Age Factors; Antipsychotic Agents; Attention Deficit and Disruptive Behavior Disorders; Benzodiazepines; Bipolar Disorder; Child; Child Development Disorders, Pervasive; Clozapine; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Tic Disorders

The aim of this study was to compare the efficacy and tolerability of quetiapine and divalproex for the treatment of impulsivity and reactive aggression in adolescents with co-occurring bipolar disorder and disruptive behavior disorders.. Patients were included in this post hoc analysis if they scored > or = 14 on the Positive and Negative Syndrome Scale (PANSS) Excited Component (EC) and > or = 4 on at least one of the PANSS EC items, had a current diagnosis of bipolar I disorder, manic or mixed episode, and had a lifetime and/or current diagnosis of a disruptive behavioral disorder (DBD) [conduct disorder (CD) or oppositional defiant disorder (ODD)]. Thirty-three (92%) of the 36 subjects with bipolar disorder and DBD met the PANSS EC inclusion criteria. These thirty-three adolescents were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 microg/mL) for 28 days in this double-blinded study. The primary efficacy measure was change in PANSS Excited Component (EC) score over the study period and at each time point.. Repeated measures analysis of variance (ANOVA) demonstrated statistically significant within-treatment-group effects for divalproex (baseline = 20.6, end point = 13.3, p < 0.0001) and quetiapine (baseline = 18.8, end point = 10.8, p < 0.0001) for the PANSS EC. There were no statistically significant treatment group differences in PANSS EC changes from baseline to end point scores (p = 0.7, d = 0.14). Mixed regression analyses (comparison of slopes, DAY*TREATMENT) revealed that there was no significant difference in the rate of improvement in the PANSS EC scores between the two treatment groups [F(1,31) = 0.78, p = 0.39, d = 0.28].. Quetiapine and divalproex showed similar efficacy for the treatment of impulsivity and reactive aggression related to co-occurring bipolar and disruptive behavior disorders in adolescents. Quetiapine and divalproex are both useful as monotherapy for the treatment of impulsivity and reactive aggression in adolescents with bipolar and disruptive behavior disorders. Placebo-controlled studies are necessary.

Topics: Adolescent; Aggression; Antimanic Agents; Antipsychotic Agents; Attention Deficit and Disruptive Behavior Disorders; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Child; Dibenzothiazepines; Double-Blind Method; Humans; Impulsive Behavior; Quetiapine Fumarate; Valproic Acid

To determine the risk of developing obesity and related metabolic complications in children following long-term treatment with risperidone or quetiapine.. This was a 1-year naturalistic longitudinal study conducted between February 2009 and March 2012. A total of 130 children aged 2 to 18 years without prior exposure to second-generation antipsychotics (SGAs) were enrolled at initiation of treatment with either risperidone or quetiapine. Metabolic parameters were measured at baseline and months 6 and 12. Data of 37 participants (20 treated with risperidone and 17 treated with quetiapine) who completed 12-month monitoring were used in the analysis.. After 1 year of SGA treatment, mean weight increased significantly by 10.8 kg (95% CI 7.9 kg to 13.7 kg) for risperidone and 9.7 kg (95% CI 6.5 kg to 12.8 kg) for quetiapine. Body mass index z score also increased significantly in both groups (P < 0.001). There was a high incidence of children becoming overweight or obese (6/15 [40.0%] for risperidone-treated and 7/14 [50.0%] for quetiapine-treated). The mean levels of fasting glucose (for risperidone-treated) and ratio of total cholesterol to high-density lipoprotein cholesterol (for quetiapine-treated) increased significantly by 0.23 mmol/L (95% CI 0.03 mmol/L to 0.42 mmol/L) and 0.48 mmol/L (95% CI 0.15 mmol/L to 0.80 mmol/L), respectively.. Children treated with risperidone or quetiapine are at a significant risk for developing obesity, elevated waist circumference, and dyslipidemia during 12 months of treatment. These data emphasize the importance of regular monitoring for early identification and treatment of metabolic side effects.

Topics: Adolescent; Antipsychotic Agents; Anxiety Disorders; Attention Deficit and Disruptive Behavior Disorders; Blood Pressure; Body Mass Index; British Columbia; Child; Child Development Disorders, Pervasive; Child, Preschool; Cholesterol; Cholesterol, HDL; Cohort Studies; Dyslipidemias; Female; Humans; Incidence; Longitudinal Studies; Male; Mental Disorders; Metabolic Syndrome; Mood Disorders; Obesity; Overweight; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Waist Circumference

Topics: Adolescent; Analysis of Variance; Antipsychotic Agents; Aripiprazole; Attention Deficit and Disruptive Behavior Disorders; Benzodiazepines; Bipolar Disorder; Body Mass Index; Body Weight; Child; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Mental Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Spain; Time Factors

Topics: Adolescent; Antipsychotic Agents; Attention Deficit and Disruptive Behavior Disorders; Child; Cross Reactions; Dibenzothiazepines; False Positive Reactions; Female; Humans; Male; Methadone; Quetiapine Fumarate; Retrospective Studies; Substance Abuse Detection

Topics: Aggression; Anticonvulsants; Attention Deficit and Disruptive Behavior Disorders; Child; Diagnosis, Differential; Dibenzothiazepines; Disruptive, Impulse Control, and Conduct Disorders; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Electroencephalography; Humans; Hyperammonemia; Lithium Chloride; Liver Function Tests; Male; Neurotoxicity Syndromes; Quetiapine Fumarate; Valproic Acid