The safety and effectiveness of open-label extended-release carbamazepine in the treatment of children and adolescents with bipolar I disorder suffering from a manic or mixed episode

Abstract

Objective

To assess the safety and effectiveness of open-label treatment with extended-release carbamazepine (ERC) in pediatric subjects suffering from bipolar I disorder.

Method

Medically healthy youths aged 10–17 years suffering from an acute manic or mixed episode were eligible. After screening for study eligibility, the youths began a 5-week titration period in which doses of ERC were adjusted in order to optimize benefit whilst minimizing adverse events, at doses between 200–1,200 mg/day. Thereafter, subjects could continue to receive treatment during a subsequent 21-week period. Safety measures included spontaneously reported adverse events (AEs) and laboratory assessments. The primary efficacy measure was the Young Mania Rating Scale (YMRS).

Results

A total of 60 children (ages 10–12) and 97 adolescents (ages 13–17), with an overall average age of 13.4 years (standard deviation [SD] 2.0 years) received ERC. The mean duration of study participation was 109.6 days (SD 70.2 days), with 66 (42%) completing the entire study. At end of study participation (end point), the most prevalent dose of ERC was 1,200 mg: 31.7% of children and 24.7% of adolescents reached the 1,200 mg dose. The YMRS decreased from a mean of 28.6 (SD 6.2) at baseline to a mean of 13.8 (SD 9.4) (P<0.0001) at end point. A total of 26 subjects discontinued study participation because of AEs, the most common of which were rash (n=6), white blood cell count decreased (n=5), nausea (n=3), and vomiting (n=3). No deaths were reported. The most commonly reported AEs were headache (n=41), somnolence (n=30), nausea (n=22), dizziness (n=21), and fatigue (n=19).

Conclusions

Open-label administration of ERC might be a safe and effective intervention in this subject population. More definitive studies are warranted.

Keywords:

• bipolar disorder
• children
• adolescents
• treatment
• carbamazpine

Acknowledgments

This study concerned a medication use that has not been approved by the US Food and Drug Administration.

Patricia A Blaine, RRT, EdM, medical writer/consultant, President of Medical Writing Corporation, provided editorial assistance for this paper, under the direction of the authors.

Disclosure

Validus Pharmaceuticals, LLC provided funding for the study.

Dr Findling receives or has received research support, acted as a consultant, received royalties from, and/or served on a speaker’s bureau for Abbott, Addrenex, Alexza, American Psychiatric Press, AstraZeneca, Biovail, Bristol-Myers Squibb, Cognition Group, Dainippon Sumitomo Pharma, Forest, GlaxoSmithKline, Guilford Press, Johns Hopkins University Press, Johnson & Johnson, KemPharm Lilly, Lundbeck, Merck, National Institutes of Health, Neuropharm, Novartis, Noven, Organon, Otsuka, Pfizer, Physicians’ Post-Graduate Press, Rhodes Pharmaceuticals, Roche, Sage, Sanofi-Aventis, Schering-Plough, Seaside Therapeutics, Sepracore, Shionogi, Shire, Solvay, Stanley Medical Research Institute, Sunovion, Supernus Pharmaceuticals, Transcept Pharmaceuticals, Validus, WebMD, and Wyeth.

In the last 12 months, Dr Ginsberg receives or has received research support, acted as a consultant, and/or served on a speaker’s bureau for AstraZeneca, Bristol Myers Squibb, Forest, Jaymac, Merck, Novartis, Noven, Otsuka, Pamlab, Pfizer, Seaside Therapeutics, Shionogi, Shire, Sunovion, and Validus.

The authors report no other conflicts of interest.