title: Management of acute agitation in patients with bipolar disorder: efficacy and safety of intramuscular aripiprazole.
abstract: To investigate the efficacy and safety of intramuscular (IM) aripiprazole for the treatment of agitation in patients with bipolar I disorder, manic or mixed episodes. In total, 301 patients experiencing acute agitation were randomized to IM aripiprazole 9.75 mg per injection (n = 78), IM aripiprazole 15 mg per injection (n = 78), IM lorazepam 2 mg per injection (n = 70), or IM placebo (n = 75) in this double-blind multicenter study. Patients could receive up to 3 injections over 24 hours. Primary efficacy measure was mean change in Positive and Negative Syndrome Scale Excited Component score from baseline at 2 hours after first injection. Mean improvements in Positive and Negative Syndrome Scale Excited Component score at 2 hours were significantly greater with IM aripiprazole (9.75 mg, -8.7; 15 mg, -8.7) and IM lorazepam (-9.6) versus IM placebo (-5.8; P <or= 0.001). For all other efficacy measures, all 3 active treatments showed significantly greater improvements over IM placebo at 2 hours (P < 0.05), with similar improvements across the active treatments. Significant differences over IM placebo were seen by 45 to 60 minutes for several efficacy parameters. Both IM aripiprazole doses were well tolerated; the safety profile was similar to oral aripiprazole. Oversedation (Agitation-Calmness Evaluation Scale score of 8 or 9) during 2 hours after first injection was less frequent with IM aripiprazole 9.75 mg (6.7%) and IM placebo (6.8%) versus IM aripiprazole 15 mg (17.3%) and IM lorazepam (19.1%). IM aripiprazole 9.75 and 15 mg are effective and well tolerated for acute agitation in bipolar disorder, although the low incidence of oversedation suggests a risk-benefit profile for IM aripiprazole 9.75 mg.
authors.affiliation: Pacific Clinical Research Medical Group, Upland, CA 91786, USA. dan.zimbroff@pcrmg.com
authors.forename: Dan L
authors.initials: DL
authors.lastname: Zimbroff
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Marcus
authors.forename: George
authors.initials: G
authors.lastname: Manos
authors.forename: Elyse
authors.initials: E
authors.lastname: Stock
authors.forename: Robert D
authors.initials: RD
authors.lastname: McQuade
authors.forename: Philippe
authors.initials: P
authors.lastname: Auby
authors.forename: Dan A
authors.initials: DA
authors.lastname: Oren
mesh_terms: D000208:Acute Disease; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000068180:Aripiprazole; D001714:Bipolar Disorder / Q000150:complications / Q000188:drug therapy*; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007273:Injections, Intramuscular; D008140:Lorazepam / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D009325:Nausea / Q000139:chemically induced; D010352:Patient Dropouts / Q000706:statistics & numerical data; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011595:Psychomotor Agitation / Q000150:complications / Q000188:drug therapy*; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; D008140:Lorazepam