New research
Asenapine for the Acute Treatment of Pediatric Manic or Mixed Episode of Bipolar I Disorder

https://doi.org/10.1016/j.jaac.2015.09.007Get rights and content
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Objective

To evaluate asenapine versus placebo in 403 patients aged 10 to 17 years with bipolar I disorder currently in manic or mixed episodes.

Method

In this double-blind, placebo-controlled, international trial, patients were randomized 1:1:1:1 to placebo, asenapine 2.5, 5, or 10 mg b.i.d. (twice daily). Primary efficacy measure was change from baseline in Young-Mania Rating Scale (YMRS) total score at day 21. Analyses of patients with/without attention-deficit/hyperactivity disorder (ADHD) and with/without stimulant use were performed.

Results

The mean difference in asenapine versus placebo in YMRS was –3.2 (p = .0008), –5.3 (p < .001), and –6.2 (p < .001) for asenapine 2.5, 5, and 10 mg b.i.d., respectively. Treatment-emergent adverse events with an incidence ≥5% and at least twice placebo were somnolence, sedation, hypoesthesia oral, paresthesia oral, and increased appetite. The asenapine groups had a higher incidence of ≥7% weight gain (range, 8.0%–12.0%) versus placebo (1.1%; p < .05). The mean change from baseline in fasting insulin was larger for patients treated with asenapine than those with placebo (asenapine 2.5 mg b.i.d.: 73.375 pmol/L; asenapine 5 mg b.i.d.: 114.042 pmol/L; asenapine 10 mg b.i.d.: 59.846 pmol/L; placebo: 3.690 pmol/L). The mean changes from baseline for lipid parameters and glucose were also larger in asenapine groups than in the placebo group. No safety differences were observed with respect to ADHD and stimulant use.

Conclusion

All asenapine doses versus placebo were superior based on change in YMRS at day 21. Asenapine was generally well tolerated in patients aged 10 to 17 years with bipolar I disorder in manic or mixed states. Increases in weight and fasting insulin were associated with asenapine.

Clinical trial registration information—Efficacy and Safety of Asenapine Treatment for Pediatric Bipolar Disorder; http://clinicaltrials.gov; NCT01244815.

Key words

asenapine
bipolar I disorder
manic episode
mixed episode

Cited by (0)

The study was designed by Merck and Co., Inc., which had direct oversight or participation in every stage of the study. All authors had full access to the data after study completion and unblinding and are responsible for the work described in this article. All authors were involved in at least 1 of the following: conception, design, acquisition, analysis, and statistical analysis, interpretation of data, and drafting the manuscript and/or revising the manuscript for important intellectual content. All authors provided final approval of the version to be published.

Ms. Braat served as the statistical expert for this research.

Tonya Goodman, BSc, of Arbor Communications, Inc., Ann Arbor, MI provided medical writing services in the preparation of this manuscript, funding for which was provided by Forest Laboratories, LLC, an Allergan affiliate.

Disclosure: Dr. Findling has received research support from, acted as a consultant to, and/or served on a speaker's bureau of Alcobra, Alexza Pharmaceuticals, the American Academy of Child and Adolescent Psychiatry, the American Physician Institute, American Psychiatric Press, Bracket, Bristol-Myers Squibb, CogCubed, Cognition Group, Coronado Biosciences, Dana Foundation, Eli Lilly and Co., Elsevier, Forest, GlaxoSmithKline, Guilford Press, Johns Hopkins University Press, Johnson and Johnson, Jubilant Clinsys, KemPharm, Lundbeck, Merck, the National Institutes of Health, Neurim, Novartis, Otsuka, Oxford University Press, Pfizer, Physicians Postgraduate Press, Purdue, Rhodes Pharmaceuticals, Roche, Sage, Shire, Sunovion, Supernus Pharmaceuticals, Transcept Pharmaceuticals, Validus, and WebMD. Dr. Landbloom is a full-time Merck employee with Merck stock. Dr. Szegedi is a former full-time Merck employee with Merck stock and is a current full-time employee of Actavis, an Allergan affiliate, with Allergan stock. Dr. Zhu is a former full-time employee of Merck and is a current full-time employee of Novartis. Dr. Mackle is a full-time employee of Merck. Dr. Chang has received research support, or has acted as a consultant for Actavis, Eli Lilly and Co., GlaxoSmithKline, Merck, and Sunovion. Dr. Mathews was employed at the time of the study by Forest Research Institute (now Actavis), an Allergan affiliate, and owns stock. Ms. Koppenhaver is a former employee of Merck and holds Merck stock. Ms. Braat is a former full-time employee of Merck.