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Intramuscular aripiprazole for the treatment of acute agitation in patients with schizophrenia or schizoaffective disorder: a double-blind, placebo-controlled comparison with intramuscular haloperidol

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Abstract

Introduction

This double-blind, placebo-controlled study investigated the efficacy and safety of intramuscular (IM) aripiprazole and IM haloperidol for the treatment of acute agitation in patients with schizophrenia or schizoaffective disorder.

Materials and methods

Four-hundred and forty-eight patients were randomized (2:2:1 ratio) to IM aripiprazole 9.75 mg, IM haloperidol 6.5 mg, or IM placebo. Patients could receive up to three injections over the first 24 h, with second and third injections administered ≥2 and ≥4 h, respectively, after the first if deemed clinically necessary. Primary efficacy measure was mean change in Positive and Negative Syndrome Scale Excited Component (PEC) score from baseline to 2 h.

Results

Mean improvement in PEC at 2 h was significantly greater for IM aripiprazole (−7.27) vs placebo (−4.78; p<0.001); IM aripiprazole was noninferior to IM haloperidol (−7.75) on PEC. All secondary efficacy measures showed significantly greater improvements at 2 h for IM aripiprazole and IM haloperidol over placebo. Mean number of injections/patient and percentage of patients requiring benzodiazepines were significantly lower for IM aripiprazole vs placebo (p<0.01). IM aripiprazole was well tolerated. Extrapyramidal symptom-related adverse events were similar for aripiprazole (1.7%) and placebo (2.3%) and lower than with haloperidol (12.6%).

Conclusion

These results show that IM aripiprazole is an effective treatment, comparable to IM haloperidol, and well-tolerated for acute agitation in patients with schizophrenia.

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Acknowledgments

We would like to thank all of the principal investigators who participated in this study: Mocrane Abbar, M.D. (Hospital Caremeau Service de Psychiatrie, Nimes, France); Jose Alvarez, M.D. (Comprehensive Neurosciences of Melbourne, Melbourne, FL, USA); Professor Raisa Andrezina (Department of Psychiatry, Riga Mental Health Care Centre, Riga, Latvia); Mohammed Abdul Bari, M.D. (Synergy Research Center, San Diego, CA, USA); Louise Beckett, M.D. (IPS Research Company, Oklahoma City, OK, USA); Miguel Bernardo-Arroyo, M.D. (Hospital Clinic Servicio de Psiquiatria, Barcelona, Spain); Daniel Bonnaffoux, M.D. (CHS du Jura, Dole, Cedex, France); Jeffrey Borenstein, M.D. (The Holliswood Hospital, Comprehensive Neuroscience Inc., Holliswood, NY, USA); Ronald Brenner, M.D. (Neurobehavioral Research, Lawrence, NY, USA); David W. Brown, M.D. (Community Clinical Research Inc., Austin, TX, USA); Richard M. Bunt, M.D. (MedPsych Specialists, Decatur, GA, USA); Osvaldo Caro, M.D. (First Hospital Panamericano, Unidad, Ponce, Puerto Rico); James C.Y. Chou, M.D. (New York University School of Medicine, Bellevue Hospital Center, NY, USA); Wlodzimierz Chrzanowski, M.D. (Samodzielny Publicczny Zaklad, Psychiatrycznej Opieki Zdrowotnej, Choroszcz K/Bialegostoku, Poland); Daniel Dassa, M.D. (Hospital Timone Adultes, Marseille, Cedex, France); Thierry Della, M.D. (Centre Hospitalier des Pyrenees, SAAU, Pau, France); Ivan Drabek, M.D. (Psychiatricka Lecebna Opava, Opava, Czech Republic); Katrin Eino, M.D. (Department of Psychiatry, North Estonia Regional Hospital, Tallinn, Estonia); Larry Ereshefsky, Pharm.D. (California Clinical Trials Medical Group, Glendale, CA, USA); David Howard Flaherty, D.O. (Segal Institute for Clinical Research, North Miami, FL, USA); Vera Pavo Filakovic, M.D. (Clinical Hospital Osijek, Psychiatric Clinic, Osijek, Croatia); Folnegovic-Smalc, M.D., Ph.D. (Psychiatric Hospital Vrapce, Zagreb, Croatia); Franco Garonna, M.D. (Azienda Sanitaria Ulss 3, Reparto Di Psichiatria Ospedale Civile, Bassano Del Grappa, Italy); Ramanath Gopalan, M.D. (Comprehensive Neurosciences of Northern Virginia, Falls Church, VA, USA); Sanjay Gupta, M.D. (Global Research and Consulting, Olean, NY, USA); George A.D. Hart, M.B., C.H.B. (Tara Hospital, Hurlingham Gauteng, South Africa); Jaromir Hons, M.D. (University Hospital Clinic of Psychiatry, Hradec Kralove, Czech Republic); Kadri Jaanson, M.D. (South Estonia Hospital, Psychiatry, Meegomae, Vorumaa, Estonia); Richard Jaffe, M.D. (Belmont Center for Comprehensive Treatment, Philadelphia, PA, USA); Jiri Janatka, M.D. (Central Military Hospital Clinic of Psychiatry, Prague, Czech Republic); Richard Josiassen, Ph.D. (Arthur P. Noyes Research Foundation, Norristown, PA, USA); Mary Ann Knesevich, M.D. (University Hills Clinical Research, Irving, TX, USA); Chandra S. Krishnasastry, M.D. (Clinical Research Services at Tennessee Christian Medical Center, Madison, TN, USA); Gunnar Larson, M.D. (C.C.R.I. Zablocki-Milwaukee VAMC, Milwaukee, WI, USA); Bum Soo Lee, M.D. (Anaheim Research Center, LLC, Anaheim, CA, USA); Michael Lesem, M.D. (Claghorn-Lesem Research Clinic, LLC, Bellaire, TX, USA); Michael T. Levy, M.D. (Behavioral Medical Research of Staten Island, Staten Island, NY, USA); Keh-Ming Lin, M.D., M.P.H. (Harbor UCLA Research and Education Institute, South Torrance, CA, USA); David E. Linden, M.D. (Linden Research Consultants, LLC, Oklahoma City, OK, USA); Adam Lowy, M.D. (Comprehensive Neuroscience Inc., Psychiatric Institute of Washington, Washington, DC, USA); Raymond Manning, M.D. (California Neuropsychopharmacology Research Institute–Los Angeles, LLC, Pico Rivera, CA, USA); David M. Marks, M.D. (Optimum Health Services, La Mesa, CA, USA); Denis Mee-Lee, M.D. (Hawaii Clinical Research Center, Honolulu, HI, USA); Ricky S. Mofsen, D.O. (Clinical Research Inc., St. Louis, MO, USA); Pavel Mohr, M.D., Ph.D. (Psychiatricke Centrum Praha, Prague, Czech Republic); Ljiljana Moro, M.D. (Clinical Hospital Rijeka, Psychiatric Clinic, Rijeka, Croatia); Izabela Niewiadomska-Marko, M.D. (Szpital IM. Jana Pawla II, Oddzial Psychiatrii, Nowy Targ, Poland); Anand K. Pandurangi, M.D. (Medical College of Virginia, Richmond, VA, USA); Michael Plopper, M.D. (Sharp Mesa Vista Hospital, San Diego, CA, USA); Pauline S. Powers, M.D. (Department of Psychiatry and Behavioral Medicine, University of South Florida, Tampa, FL, USA); Sohail Punjwani, M.D. (Segal Institute for Clinical Research, North Miami, FL, USA); Ants Puusild, M.D. (Parnu Hospital, Department of Psychiatry, Parnu, Estonia); Jiri Raboch, M.D. (General University Hospital Clinic of Psychiatry, Prague, Czech Republic); Joachim D. Raese, M.D. (Behavioral Health 2000, LLC, Riverside, CA, USA); Rakesh Ranjan, M.D. (Rakesh Ranjan, M.D., and Associates Inc., Lyndhurst, OH, USA); Paulis Revelis, M.D. (Jelgava Psychiatry Hospital, Jelgava, Latvia); Vitalijs Rodins, M.D. (Department of Psychiatry, Strenci Psychiatry Hospital, Strenci, Latvia); David Sack, M.D. (Comprehensive Neuroscience Inc., Cerritos, CA, USA); Scott Daniel Segal, M.D. (Segal Institute for Clinical Research, North Miami, FL, USA); Anantha Shekhar, M.D., Ph.D. (Indiana University Adult Psychiatry, Indianapolis, IN, USA); Michael Smith, M.D. (Harbor UCLA Research and Education Institute, South Torrance, CA, USA); Richard M. Steinbook, M.D. (Department of Psychiatry, University of Miami School of Medicine, Miami, FL, USA); Jaroslaw Strzelec, M.D. (NZOZ Wolmed, Dubie GM. Szczercow, Dubie, Poland); Jaromir Svestka, M.D. (University Hospital Clinic of Psychiatry, Brno-Bohunice, Czech Republic); Tram K. Tran-Johnson, Pharm.D., Psy.D. (California Neuropsychopharmacology Clinical Research Institute–San Diego, LLC, San Diego, CA, USA); Madeleine M. Valencerina, M.D. (Neogenics Clinical Trials, La Palma, CA, USA); Nadine Wertenschlag, M.D. (Etablissement Public de Sante Alsace, Nord Service du Dr. Brunner, Brumath, Cedex, France); Georges Zaykine, M.D. (Clinique Sainte-Therese, Narbonne, France); Dan L. Zimbroff, M.D. (Pacific Clinical Research Medical Group, Upland, CA, USA).

This study was supported by Bristol-Myers Squibb Company (Princeton, NJ) and Otsuka Pharmaceutical Co., Ltd. (Tokyo, Japan).

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Authors and Affiliations

  1. Department of Psychiatry, Riga Mental Health Care Centre, Tvaika Street 2, Riga, 1005, Latvia

    Raisa Andrezina

  2. Arthur P. Noyes Research Foundation, Department of Psychiatry, University of Pennsylvania, 1001 Sterigere Street, Norristown, PA, 19401, USA

    Richard C. Josiassen

  3. Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT, 06492, USA

    Ronald N. Marcus, Dan A. Oren, George Manos & Elyse Stock

  4. Otsuka America Pharmaceutical Inc., 100 Overlook Drive, Princeton, NJ, 08540, USA

    William H. Carson

  5. Otsuka Pharmaceutical Co. Ltd., 2-9 Kanda Tsukasa-cho, Chiyoda-ku, Tokyo, 101 8535, Japan

    Taro Iwamoto

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  1. Raisa Andrezina
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  2. Richard C. Josiassen
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  3. Ronald N. Marcus
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  4. Dan A. Oren
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  5. George Manos
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  6. Elyse Stock
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  7. William H. Carson
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  8. Taro Iwamoto
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Correspondence to Richard C. Josiassen.

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Joint first authorship for authors Raisa Andrezina and Richard Josiassen.

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Andrezina, R., Josiassen, R.C., Marcus, R.N. et al. Intramuscular aripiprazole for the treatment of acute agitation in patients with schizophrenia or schizoaffective disorder: a double-blind, placebo-controlled comparison with intramuscular haloperidol. Psychopharmacology 188, 281–292 (2006). https://doi.org/10.1007/s00213-006-0541-x

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  • DOI: https://doi.org/10.1007/s00213-006-0541-x

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