Acute Treatment of Mania in Children and Adolescents
Acute Treatment of Mania in Children and Adolescents
Of several recent reviews of the efficacy of second-generation antipsychotics (SGAs) for treating children and adolescents who have mania, a review by Liu et al. is the most comprehensive, as the authors were able to access the results of both published and unpublished trials. The summary that follows is derived from the review by Liu et al., supplemented by information available on the Clinical Trials Register (www.clinicaltrials.gov).
We identified four published randomized placebo-controlled trials of SGAs [aripiprazole (2), olanzapine, risperidone], two unpublished trials (quetiapine, ziprasidone), and two more in progress (clozapine for treatment refractory mania, paliperidone). Sample sizes ranged from 41 (aripiprazole 1) to 296 (aripiprazole 2). Participants were typically 10–17 years old, met criteria for bipolar I (the aripiprazole trials also permitted bipolar II) and were experiencing a manic or mixed episode. Trials commonly permitted ADHD, oppositional defiant disorder (ODD), conduct disorder and anxiety comorbidity but excluded other psychiatric conditions. It was not clear in most cases if patients were naive to antipsychotic medication. Trials ranged in duration from 21 to 42 days. Two trials (aripiprazole 2 and quetiapine) randomized participants to one of two fixed doses of medication or placebo, whereas other trials titrated to effect and tolerability. The smaller aripiprazole trial permitted concurrent treatment with psychostimulant medication. Response in each of the trials was defined as a 50% reduction in scores on the Young Mania Rating Scale.
All of these trials favoured active treatment over placebo and differences in response rates were statistically significant. Response rates to active treatment ranged from 49 to 89%, whereas response to placebo ranged from 22 to 52%. A meta-regression found that mean age was not associated with response rate in the clinical trials,. We were able to calculate numbers needed to treat (NNT) for each trial, which are summarized in Table 1 .
Two reviews of the tolerability of SGAs approached the topic in different ways. Liu et al. combined data from open-label and randomized controlled trials (RCTs) to provide a descriptive report of common adverse events for each drug. These data are summarized in Table 2 .
Fraguas et al. reviewed open-label and randomized trials of SGA for both schizophrenia and bipolar spectrum disorders, focusing on weight gain, metabolic and cardiovascular parameters, prolactin levels and neuromotor symptoms. Consistent with the descriptive data reported in Table 2 , in the RCTs for bipolar disorder, Fraguas et al. found statistically significant increases in BMI when adolescents were treated with olanzapine and higher doses of risperidone, but not when they were prescribed aripiprazole. Differences were also nonsignificant for treatment with quetiapine and lower doses of risperidone. Drug–placebo differences in mean glucose levels were nonsignificant when adolescents were treated with olanzapine and risperidone and unavailable for other SGAs. Mean cholesterol level increases for aripiprazole, olanzapine, quetiapine, and risperidone were nonsignificant. Increases in mean triglyceride levels were statistically significant for olanzapine but nonsignificant for aripiprazole, quetiapine, and risperidone. Increases in mean prolactin levels were statistically significant for olanzapine and risperidone, and nonsignificant for quetiapine. When available, rates of patients developing dystonia, rigidity, tremor and akathisia were mildly elevated compared with patients who received placebo, but no difference reached statistical significance.
Second-generation Antipsychotics
Of several recent reviews of the efficacy of second-generation antipsychotics (SGAs) for treating children and adolescents who have mania, a review by Liu et al. is the most comprehensive, as the authors were able to access the results of both published and unpublished trials. The summary that follows is derived from the review by Liu et al., supplemented by information available on the Clinical Trials Register (www.clinicaltrials.gov).
We identified four published randomized placebo-controlled trials of SGAs [aripiprazole (2), olanzapine, risperidone], two unpublished trials (quetiapine, ziprasidone), and two more in progress (clozapine for treatment refractory mania, paliperidone). Sample sizes ranged from 41 (aripiprazole 1) to 296 (aripiprazole 2). Participants were typically 10–17 years old, met criteria for bipolar I (the aripiprazole trials also permitted bipolar II) and were experiencing a manic or mixed episode. Trials commonly permitted ADHD, oppositional defiant disorder (ODD), conduct disorder and anxiety comorbidity but excluded other psychiatric conditions. It was not clear in most cases if patients were naive to antipsychotic medication. Trials ranged in duration from 21 to 42 days. Two trials (aripiprazole 2 and quetiapine) randomized participants to one of two fixed doses of medication or placebo, whereas other trials titrated to effect and tolerability. The smaller aripiprazole trial permitted concurrent treatment with psychostimulant medication. Response in each of the trials was defined as a 50% reduction in scores on the Young Mania Rating Scale.
All of these trials favoured active treatment over placebo and differences in response rates were statistically significant. Response rates to active treatment ranged from 49 to 89%, whereas response to placebo ranged from 22 to 52%. A meta-regression found that mean age was not associated with response rate in the clinical trials,. We were able to calculate numbers needed to treat (NNT) for each trial, which are summarized in Table 1 .
Two reviews of the tolerability of SGAs approached the topic in different ways. Liu et al. combined data from open-label and randomized controlled trials (RCTs) to provide a descriptive report of common adverse events for each drug. These data are summarized in Table 2 .
Fraguas et al. reviewed open-label and randomized trials of SGA for both schizophrenia and bipolar spectrum disorders, focusing on weight gain, metabolic and cardiovascular parameters, prolactin levels and neuromotor symptoms. Consistent with the descriptive data reported in Table 2 , in the RCTs for bipolar disorder, Fraguas et al. found statistically significant increases in BMI when adolescents were treated with olanzapine and higher doses of risperidone, but not when they were prescribed aripiprazole. Differences were also nonsignificant for treatment with quetiapine and lower doses of risperidone. Drug–placebo differences in mean glucose levels were nonsignificant when adolescents were treated with olanzapine and risperidone and unavailable for other SGAs. Mean cholesterol level increases for aripiprazole, olanzapine, quetiapine, and risperidone were nonsignificant. Increases in mean triglyceride levels were statistically significant for olanzapine but nonsignificant for aripiprazole, quetiapine, and risperidone. Increases in mean prolactin levels were statistically significant for olanzapine and risperidone, and nonsignificant for quetiapine. When available, rates of patients developing dystonia, rigidity, tremor and akathisia were mildly elevated compared with patients who received placebo, but no difference reached statistical significance.
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