Bipolar disorder in children and adolescents is a serious illness that adversely affects family, peers, and academic functioning. It increases risk for suicidality and is associated with high rates of occurrence. Bipolar depression presents a significant treatment challenge for clinicians. Although selective serotonin reuptake inhibitors are effective in the treatment of depression, they pose a risk of mania in children with bipolar disorder. There are now two FDA-approved medications: lurasidone and olanzapine/fluoxetine for the treatment of bipolar I depression in children and adolescents aged 10 to 17 years.
The efficacy and safety of lurasidone was investigated in a double-blind, placebo-controlled study of 347 youth aged 10 to 17 years with a diagnosis of bipolar I depression.1 Patients were randomized to lurasidone (n = 175) or placebo (n = 172) in this 6-week treatment study: 92% of the lurasidone group and 89.7% of the placebo group completed 6 weeks of treatment. The dose range of lurasidone was 20 to 80 mg daily, with a mean dose of 33.6 mg daily.
There was a statically significant difference from baseline to week 6 in the primary efficacy measure, Children’s Depression Rating Scale-Revised (CDRS-R) total score, between the lurasidone and placebo groups, favoring lurasidone. The effect size was medium, 0.45. Response rates (defined as ≥50% reduction from baseline to week 6 in CDRS-R total score) were significantly higher in the lurasidone group compared with the placebo group (59.5% vs 36.5%). The most frequent adverse events for the lurasidone were nausea and somnolence. There were no significant differences between the lurasidone and placebo groups on measures of suicidality, treatment-emergent mania, akathisia and extrapyramidal symptoms, cognitive function, weight and BMI, and lipid, glucose and prolactin levels.
The efficacy and safety of the olanzapine/fluoxetine combination (OFC) was evaluated in a double-blind placebo-controlled trial of 255 youths aged 10 to 17 years with bipolar I depression.2 Patients were randomized to OFC (n = 170) or placebo (n = 85) in this 8-week trial: 68.2% of the OFC group and 70.5% of the placebo group completed 8 weeks of treatment. The dose range of OFC was 6/25 to 12/50 mg daily with a mean dose of 7.7/37.6 mg daily.
There was a statically significant difference from baseline to week 8 in the primary efficacy measure, CDRS-R total score, between the OFC and placebo groups, favoring OFC. The effect size was medium, 0.46. Response rates (defined as ≥ 50% reduction from baseline to week 8 in CDRS-R total score and Young Mania Rating Scale item 1 score ≤2 at endpoint) were more significantly higher in the OFC group compared with the placebo group (78.2% vs 59.2%). Adverse events that were statistically significantly more in the OFC than the placebo-treated patients were weight gain, appetite increase, somnolence, sedation, and tremor. Mean weight gain for OFC-treated patients compared with placebo-treated patients was significantly greater (4.4 kg vs 0.5 kg). Patients in the OFC group had significantly greater increase in fasting total cholesterol, triglycerides, prolactin, and hepatic analytes. There were no significant differences in extrapyramidal symptoms and measures of suicidality between the patients receiving OFC and those patients receiving placebo.
Dr. Wagner is Professor and Chair, Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston, TX. She is President of the American Academy of Child and Adolescent Psychiatry.
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