Atomoxetine as an adjunct therapy in the treatment of co-morbid attention-deficit/hyperactivity disorder in children and adolescents with bipolar I or II disorder.

INTRODUCTION: Atomoxetine has been proposed to be effective for treating co-morbid attention-deficit/hyperactivity disorder (ADHD) in children with bipolar disorder (BPD) without destabilizing mood. We conducted an 8-week, open label study to study the efficacy and tolerability of adjunct atomoxetine in euthymic children and adolescents with BPD and ADHD. METHODS: We evaluated 12 youth aged 6-17 years (mean = 11.3 years; 7 males) with a diagnosis of BPD I or II and ADHD. Subjects were euthymic at baseline and taking at least one mood stabilizer or antipsychotic. Primary outcome measure was the ADHD Rating Scale-IV (ADHD-RS-IV) (response = 25% decrease; remission = 40% decrease). Secondary outcome measures were change in Young Mania Rating Scale (YMRS) and Children's Depression Rating Scale (CDRS). RESULTS: In primary outcome criteria, 8 (67%) were responders and 6 (50%) were remitters by ADHD-RS criteria. There was a significant decrease in ADHD-RS scores over the study (p < 0.0001; Cohen d = 2.18, effect size = 0.73). YMRS and CDRS scores did not change significantly from baseline to week 8. No subjects experienced a manic or mixed episode during the study, but 2 subjects were discontinued early due to worsening of mood symptoms. CONCLUSIONS: We found atomoxetine to be efficacious in treating symptoms of ADHD in children and adolescents with BPD taking mood stabilizers or antipsychotics. It is unclear whether symptomatic worsening of 2 subjects was due to atomoxetine or the natural course of illness. Placebo-controlled studies are needed to clarify the role of atomoxetine in this population.

A double-blind, placebo-controlled pilot study of quetiapine for depressed adolescents with bipolar disorder.

OBJECTIVE: To conduct a pilot study comparing the effects of quetiapine and placebo for the treatment of depressive episodes in adolescents with bipolar I disorder. METHOD: Thirty-two adolescents (ages 12-18 years) with a depressive episode associated with bipolar I disorder were randomized to eight weeks of double-blind treatment with quetiapine, 300-600 mg/day, or placebo. This two-site study was conducted from March 2006 through August 2007. The primary efficacy measure was change in Children's Depression Rating Scale-Revised Version (CDRS-R) scores from baseline to endpoint. Secondary efficacy measures included change in CDRS-R scores over the eight-week study period (PROC MIXED), changes from baseline to endpoint in Hamilton Anxiety Rating Scale (HAM-A), Young Mania Rating Scale (YMRS), and Clinical Global Impression-Bipolar Version Severity (CGI-BP-S) scores, as well as response and remission rates. Safety and tolerability were assessed weekly. RESULTS: There was no statistically significant treatment group difference in change in CDRS-R scores from baseline to endpoint (p = 0.89, effect size =-0.05, 95% confidence interval: -0.77-0.68), nor in the average rate of change over the eight weeks of the study (p = 0.95). Additionally, there were no statistically significant differences in response (placebo =67% versus quetiapine = 71%) or remission (placebo = 40% versus quetiapine = 35%) rates, or change in HAM-A, YMRS, or CGI-BP-S scores (all p > 0.7) between treatment groups. Dizziness was more commonly reported in the quetiapine (41%) than in the placebo (7%) group (Fisher's exact test, p = 0.04). CONCLUSIONS: The results suggest that quetiapine monotherapy is no more effective than placebo for the treatment of depression in adolescents with bipolar disorder. However, limitations of the study, including the high placebo response rate, may have contributed to our findings and should be considered in the design of future investigations of pharmacological interventions for this population.

Divalproex sodium in the treatment of pediatric psychiatric disorders.

Divalproex sodium is an anticonvulsant that is used extensively in adults with indications for epilepsy, acute mania and migraine prophylaxis. It has been used in children and adolescents as a first-line agent for mania in bipolar disorder. Its efficacy as a mood stabilizer has been established, and there have been studies outlining its efficacy as an agent effective in the treatment of conduct disorder, disruptive behavior disorders, aggression and explosive disorder. Longer-acting formulations are now available that cause less gastrointestinal side effects and can also be taken once a day, thus potentially increasing adherence, an important factor in this patient population. Future directions would include developing a more potent valproic acid formulation with fewer side effects, completing randomized controlled trials to establish the efficacy of divalproex sodium in various other pediatric psychiatric disorders, establishing the relative efficacy of the compound in head-to-head comparisons with other mood stabilizers, examining systematically the value of the compound in multimodal pediatric psychiatric treatment packages, and complete effectiveness trials that demonstrate the short- and long-term effectiveness of the compound in the real world of clinicians. In this drug profile, divalproex sodium and its uses in the pediatric population for psychiatric conditions are reviewed.