title: Asenapine for the Acute Treatment of Pediatric Manic or Mixed Episode of Bipolar I Disorder.
abstract: OBJECTIVE
  To evaluate asenapine versus placebo in 403 patients aged 10 to 17 years with bipolar I disorder currently in manic or mixed episodes.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Johns Hopkins University and the Kennedy Krieger Institute, Baltimore. Electronic address: rfindli1@jhmi.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.affiliation: Merck, Whitehouse Station, NJ.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Landbloom
authors.affiliation: Merck during the course of the study; Actavis, an Allergan affiliate, Jersey City, NJ.
authors.forename: Armin
authors.initials: A
authors.lastname: Szegedi
authors.affiliation: Merck during the course of the study.
authors.forename: Janelle
authors.initials: J
authors.lastname: Koppenhaver
authors.affiliation: Merck, Oss, The Netherlands.
authors.forename: Sabine
authors.initials: S
authors.lastname: Braat
authors.affiliation: Merck, Oss, The Netherlands, during the course of the study; Novartis, Shanghai.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Merck, Whitehouse Station, NJ.
authors.forename: Mary
authors.initials: M
authors.lastname: Mackle
authors.affiliation: Lucille Packard Children's Hospital, Stanford University School of Medicine, Stanford, CA.
authors.forename: Kiki
authors.initials: K
authors.lastname: Chang
authors.affiliation: Forest Research Institute (now Actavis), an Allergan affiliate; Janssen Pharmaceuticals, Titusville, NJ.
authors.forename: Maju
authors.initials: M
authors.lastname: Mathews
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D003986:Dibenzocycloheptenes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D016015:Logistic Models; D008297:Male; D011569:Psychiatric Status Rating Scales; D012426:Russia; D014481:United States
chemical_list: D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D001569:Benzodiazepines; C522667:asenapine
keywords: asenapine; bipolar I disorder; manic episode; mixed episode