title: A randomized, placebo- and active-controlled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorder.
abstract: OBJECTIVE
  To evaluate the antimanic efficacy and safety of paliperidone extended-release (ER) tablets in patients with bipolar I disorder.
  
  
  METHODS
  This study included a 3-week, double-blind, acute treatment phase (paliperidone ER versus placebo, with quetiapine as control), and a 9-week, double-blind, maintenance phase (paliperidone ER versus quetiapine). Patients [n = 493; Young Mania Rating Scale (YMRS) score >or= 20] were randomized (2:2:1) to flexibly dosed paliperidone ER (3-12 mg/day), quetiapine (400-800 mg/day), or placebo for the acute treatment phase. During the maintenance phase, patients assigned to placebo were switched to paliperidone ER but not included in analysis of efficacy.
  
  
  RESULTS
  Paliperidone ER was superior to placebo at the 3-week endpoint {primary outcome; least-squares mean difference in change from baseline in YMRS scores [95% confidence interval (CI)]: -5.5 (-7.57; -3.35); p < 0.001} and noninferior to quetiapine at the 12-week endpoint [least-squares mean difference (95% CI): 1.7 (-0.47; 3.96)]. The median mode dose during the 12-week treatment period was 9 mg for paliperidone ER and 600 mg for quetiapine. The most common (>or= 10%) treatment-emergent adverse events during the 12-week period were: headache (16%), somnolence (10%), and akathisia (10%) for paliperidone ER; somnolence (21%), sedation and dry mouth (17% each), headache (14%), and dizziness (13%) for quetiapine. Body weight increase >or= 7% from baseline to 12-week endpoint was 8% with paliperidone ER and 17% with quetiapine. A higher percentage of paliperidone ER (13.9%) versus quetiapine patients (7.5%) 'switched to depression' at the12-week endpoint.
  
  
  CONCLUSIONS
  Paliperidone ER (3-12 mg/day) was efficacious and tolerable in the treatment of acute mania.
authors.affiliation: Institute of Neuroscience, University of Barcelona Hospital Clinic, IDIBAPS, CIBERSAM, Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.forename: Isaac F
authors.initials: IF
authors.lastname: Nuamah
authors.forename: Pilar
authors.initials: P
authors.lastname: Lim
authors.forename: Eric C
authors.initials: EC
authors.lastname: Yuen
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Palumbo
authors.forename: David W
authors.initials: DW
authors.lastname: Hough
authors.forename: Joris
authors.initials: J
authors.lastname: Berwaerts
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000145:classification / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000627:therapeutic use; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011569:Psychiatric Status Rating Scales; D011743:Pyrimidines / Q000627:therapeutic use*; D000069348:Quetiapine Fumarate; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D007555:Isoxazoles; D011743:Pyrimidines; D000069348:Quetiapine Fumarate; D000068882:Paliperidone Palmitate