NR275
Monday, May 23, 3:00 p.m.-5:00 p.m.

Intramuscular Aripiprazole Versus Placebo for Agitation in Acute Mania

Dan Oren, M.D., Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492; Taro Iwamoto, Ph.D., Ronald Marcus, M.D., Simon Vanveggel, M.S.C., Robert McQuade, Ph.D., Elyse G. Stock, M.D., Frank Yocca, Ph.D.

Educational Objectives:
At the conclusion of the presentation, the participant should be able to describe the intramuscular use of medications in acutely agitated patients with bipolar mania.

Summary:

Objective: To compare the efficacy of intramuscular (IM) aripiprazole and IM lorazepam with placebo in acutely agitated patients with a manic or mixed episode in bipolar 1 disorder.
Methods: This double-blinded, randomized, multicenter study compared two doses of IM aripiprazole (10 mg and 15 mg), lorazepam (2 mg), and placebo. The first injection was followed by inpatient evaluation for 24 hours. If needed, a second injection was given >2 hours post-initial injection and a third injection, if needed, >2 hours post-second injection. Primary efficacy measure was the mean change from baseline to two hours (LOCF), postinitial IM injection, in the PANSS Excited Component (PEC) score.
Results: Mean changes from baseline in PEC scores two hours post-initial IM injection were aripiprazole 10 mg (n=75), -8.7; aripiprazole 15 mg (n=75), -8.7; lorazepam 2 mg (n=68), -9.6, placebo (n=73), -5.8 (all active drugs p<0.001 vs. placebo). Aripiprazole was well tolerated in this study.
Conclusion: Aripiprazole IM shows efficacy significantly improved over placebo and similar to that of IM lorazepam in the treatment of agitation in patients with bipolar I disorder, manic or mixed.

References:
1. Keck PE, Marcus R, Tourkodimitris S, Ali M, Liebeskind A, Saha A, Ingenito G: A placebo-controlled, double-blind study of the efficacy and safety of aripiprazole in patients with acute bipolar mania. Am J Psychiatry 2003; 160:1651-1658.
2. R Gismondi, D Daniel, E Stock, R Wilber, R Marcus,WCarson, G Manos, T Iwamoto: Intramuscular aripiprazole treatment for acute agitation in patients with psychosis Neuropsychopharm 2004; 14(suppl 3):S261.

Frank Yocca, B.Ph., Department of Neuroscience Biology, Bristol-Myers Squibb Company, PO Box 5100, 5 Research Parkway, Wallingford, CT 06492; Ronald Marcus, M.D., Dan Oren, M.D., George Manos, Ph.D., William H. Carson, Jr., M.D., Taro Iwamoto, Ph.D., Elyse Stock, M.D.

Educational Objectives:
At the conclusion of the presentation, the participant should be able to describe the use of intramuscular formulations of typical and atypical antipsychotics in acutely agitated patients with schizophrenia or schizoaffective disorder.

Summary:

Objective: Compare the efficacy of intramuscular (IM) aripiprazole and haloperidol IM with placebo in acutely agitated patients with schizophrenia or schizoaffective disorder.
Methods: In this double-blind trial, patients were randomized to IM aripiprazole 10 mg, IM haloperidol 6.5 mg or placebo in a 2:2:1 fashion. The first injection was followed by inpatient evaluation for 24 hours. If needed, a second injection was given >2 hours post-initial injection and a third injection, if needed >2 hours post-second injection. For patients randomized to placebo, the third dose contained 10 mg aripiprazole. Primary efficacy measure was the mean change from baseline to two hours (LOCF) post-initial IM injection in the PANSS Excited Component (PEC) score. Patients completing the 24-hour IM phase continued their blinded treatment with tablets/capsules for four days.
Results: Mean changes from baseline in PEC scores two hours post-initial IM injection were aripiprazole (n=173), -7.3; haloperidol (n=184), -7.8; placebo (n=88), -4.8 (p<0.001 for both drugs vs. placebo). Mean CGI-I scores two hours post-initial IM injection were aripiprazole, 2.4; haloperidol, 2.4; placebo, 3.1 (p<0.001 vs. aripiprazole/haloperidol). Aripiprazole was well tolerated.
Conclusions: Aripiprazole IM shows greater efficacy than placebo and comparable efficacy to haloperidol IM in acutely agitated patients with schizophrenia or schizoaffective disorder.

References:
1. Gismondi R, Daniel D, Stock E, Wilber R, Marcus R, Carson W, Manos G, Iwamoto T: Intramuscular aripiprazole treatment for acute agitation in patients with psychosis Neuropsychopharm 2004; 14(suppl 3): S261.
2. Zimbroff DL: Management of acute psychosis: from emergency to stabilization. CNS Spectr 2003; 8(11 Suppl 2): 10-15.