Pharmacopsychiatry 2008; 41(5): 182-189
DOI: 10.1055/s-2008-1077050
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Treatment of Severe Agitation with Olanzapine in 166 Patients with Schizophrenia, Schizoaffective, or Bipolar I Disorder

M. Lambert 1 [*] , C. G. Huber 1 [*] , D. Naber 1 , A. Schacht 2 , T. T. Wagner 2 , H.-P. Hundemer 2 , A. Karow 1 , B. G. Schimmelmann 3
  • 1Psychosis Early Detection and Intervention Centre (PEDIC), Centre for Psychosocial Medicine, Department of Psychiatry and Psychotherapy, University Medical Centre, Hamburg-Eppendorf, Germany
  • 2Medical Neuroscience Department, Lilly Deutschland GmbH, Bad Homburg, Germany
  • 3Department of Child and Adolescent Psychiatry, University Duisburg-Essen, Duisburg, Germany
Further Information

Publication History

received 28.09.2007 revised 02.02.2008

accepted 03.03.2008

Publication Date:
01 September 2008 (online)

Abstract

Introduction: Agitation is a common phenomenon in schizophrenia or acute mania. Because of the inability of patients to give informed consent in such situations, data from consenting studies are limited.

Methods: This observational prospective 5-day study evaluated the effectiveness of olanzapine in a sample of highly agitated patients with aggression. Primary endpoint was mean change of the PANSS-Excited Component (PANSS-EC) score.

Results: Mean PANSS-EC score at baseline was 25.5 points, 60.2% were severely agitated and 41.6% severely aggressive. A significant decrease in PANSS-EC total score (−13.3 points) was observed with rapid dose escalation and an average daily dose of 21.2 mg/day of olanzapine. 40 patients (24.1%) required treatment with another antipsychotic and 21 patients (12.7%) were not treated with olanzapine at day 5. At endpoint, 64.2% of patients were in remission of agitation. PANSS-EC reduction was not significantly different in patients with or without concurrent benzodiazepine use.

Discussion: Severe agitation with aggression may be well controlled with olanzapine in many cases, possibly by higher initial and overall doses of olanzapine. Controlled studies are needed to confirm these findings.

References

  • 1 Allen MH, Currier GW, Carpenter D, Ross RW, Docherty JP. Treatment of behavioral emergencies 2005.  J Psychiatr Pract. 2005;  11 ((Suppl 1)) 5-108
  • 2 Allen MH, Currier GW, Hughes DH, Docherty JP, Carpenter D, Ross R. Treatment of behavioral emergencies: a summary of the expert consensus guidelines.  J Psychiatr Pract. 2003;  9 16-38
  • 3 Allen MH, Currier GW, Hughes DH, Reyes-Harde M, Docherty JP. The Expert Consensus Guideline Series. Treatment of behavioral emergencies.  Postgraduate medicine. 2001;  1-88
  • 4 Andreasen NC, Carpenter Jr WT, Kane JM, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus.  Am J Psychiatry. 2005;  162 441-449
  • 5 Baker RW, Kinon BJ, Maguire GA, Liu H, Hill AL. Effectiveness of rapid initial dose escalation of up to forty milligrams per day of oral olanzapine in acute agitation.  J Clin Psychopharmacol. 2003;  23 342-248
  • 6 Barbee JG, Mancuso DM, Freed CR, Todorov AA. Alprazolam as a neuroleptic adjunct in the emergency treatment of schizophrenia.  Am J Psychiatry. 1992;  149 506-510
  • 7 Battaglia J. Pharmacological management of acute agitation.  Drugs. 2005;  65 1207-1222
  • 8 Bitter I, Czobor P, Dossenbach M, Volavka J. Effectiveness of clozapine, olanzapine, quetiapine, risperidone, and haloperidol monotherapy in reducing hostile and aggressive behavior in outpatients treated for schizophrenia: a prospective naturalistic study (IC-SOHO).  Eur Psychiatry. 2005;  20 403-408
  • 9 Breier A, Meehan K, Birkett M, David S, Ferchland I, Sutton V. et al . A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia.  Arch Gen Psychiatry. 2002;  59 441-448
  • 10 Briken P, Nika E, Krausz M, Naber D. Atypical neuroleptics in the treatment of aggression and hostility in schizophrenic patients.  Fortschr Neurol Psychiatr. 2002;  70 139-144
  • 11 Currier GW, Chou JC, Feifel D, Bossie CA, Turkoz I, Mahmoud RA. et al . Acute treatment of psychotic agitation: a randomized comparison of oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam.  J Clin Psychiatry. 2004;  65 386-394
  • 12 Czekalla J, Siemer A, Wagner TT, Wilhelm S, Lambert M. Benzodiazepine co-medication of acutely aggressive psychiatric inpatients treated with olanzapine and other antipsychotics. Poster presented at the XIIIth Biennial Workshop on Schizophrenia Research, Davos, Switzerland, February 4–10, 2006.  Schizophr Res. 2006;  81 78-79
  • 13 Eli Lilly and Company .Zyprexa [US Product Information]. Indianapolis 2006
  • 14 Emsley R, Oosthuizen P. Evidence-based pharmacotherapy of schizophrenia.  Int J nNeuropsychopharmacol. 2004;  7 219-238
  • 15 Goedhard LE, Stolker JJ, Heerdink ER, Nijman HL, Olivier B, Egberts TC. Pharmacotherapy for the treatment of aggressive behavior in general adult psychiatry: A systematic review.  J Clin Psychiatry. 2006;  67 1013-1024
  • 16 Goedhard LE, Stolker JJ, Nijman HL, Egberts AC, Heerdink ER. Aggression of psychiatric patients associated with the use of as-needed medication.  Pharmacopsychiatry. 2007;  40 25-29
  • 17 Guy W. Clinical global impression. In: Guy W (ed). ECDEU Assessment Manual for Psychopharmacology, revised. Rockville, MI: National Insitute of Mental Health 1976: 217-222
  • 18 Haro JM, Kamath SA, Ochoa S, Novick D, Rele K, Fargas A. et al . The Clinical Global Impression-Schizophrenia scale: a simple instrument to measure the diversity of symptoms present in schizophrenia.  Acta Psychiatr Scand Suppl. 2003;  1 16-23
  • 19 Hofer A, Rettenbacher MA, Edlinger M, Huber R, Bodner T, Kemmler G. et al . Outcomes in schizophrenia outpatients treated with amisulpride or olanzapine.  Pharmacopsychiatry. 2007;  40 1-8
  • 20 Huber CG, Lambert M, Naber D, Schacht A, Hundemer H-P, Wagner TT. et al . Validation of a Clinical Global Impression Scale for Aggression (CGI-A) in a sample of 558 psychiatric patients.  Schizophr Res. , , in press
  • 21 Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia.  Schizophr Bull. 1987;  13 261-276
  • 22 Keck Jr PE. The role of second-generation antipsychotic monotherapy in the rapid control of acute bipolar mania.  J Clin Psychiatry. 2005;  66 ((Suppl 3)) 5-11
  • 23 Kennedy JS, Jeste D, Kaiser CJ, Golshan S, Maguire GA, Tollefson G. et al . Olanzapine vs haloperidol in geriatric schizophrenia: analysis of data from a double-blind controlled trial.  Int J Geriatr Psychiatry. 2003;  18 1013-1020
  • 24 Krakowski MI, Czobor P, Citrome L, Bark N, Cooper TB. Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder.  Arch Gen Psychiatry. 2006;  63 622-629
  • 25 Lambert M, Conus P, Lambert T, MacGorry PD. Pharmacotherapy of first-episode psychosis.  Expert Opin Pharmacother. 2003;  4 717-750
  • 26 Lindenmayer JP. The pathophysiology of agitation.  J Clin Psychiatry. 2000;  61 ((Suppl 14)) 5-10
  • 27 Lindenmayer JP, Czobor P, Alphs L, Nathan AM, Anand R, Islam Z. et al . The InterSePT scale for suicidal thinking reliability and validity.  Schizophr Res. 2003;  63 161-170
  • 28 Mallinckrodt CH, Clark WS, David SR. Accounting for dropout bias using mixed-effects models.  J Biopharm Stat. 2001;  11 9-21
  • 29 Mallinckrodt CH, Kaiser CJ, Watkin JG, Molenberghs G, Carroll RJ. The effect of correlation structure on treatment contrasts estimated from incomplete clinical trial data with likelihood-based repeated measures compared with last observation carried forward ANOVA.  Clin Trials. 2004;  1 477-489
  • 30 Marco CA, Vaughan J. Emergency management of agitation in schizophrenia.  Am J Emerg Med. 2005;  23 767-776
  • 31 Pascual JC, Madre M, Soler J, Barrachina J, Campins MJ, Alvarez E. et al . Injectable atypical antipsychotics for agitation in borderline personality disorder.  Pharmacopsychiatry. 2006;  39 117-118
  • 32 Poser W, Poser S. Abuse of and dependence on benzodiazepines.  Internist (Berl). 1986;  27 738-745
  • 33 Robinson D, Woerner MG, Pollack S, Lerner G. Subject selection biases in clinical trials: data from a multicenter schizophrenia treatment study.  J Clin Psychopharmacol. 1996;  16 170-176
  • 34 Sachs GS. Treatment of agitation with atypical antipsychotics in bipolar affective disorder.  Am J Psychiatry. , , in press
  • 35 San L, Arranz B, Querejeta I, Barrio S, Gandara J De la, Perez V. A naturalistic multicenter study of intramuscular olanzapine in the treatment of acutely agitated manic or schizophrenic patients.  Eur Psychiatry. 2006;  21 539-543
  • 36 Spearing MK, Post RM, Leverich GS, Brandt D, Nolen W. Modification of the Clinical Global Impressions (CGI) Scale for use in bipolar illness (BP): the CGI-BP.  Psychiatry Res. 1997;  73 159-171
  • 37 Turczynski J, Bidzan L, Staszewska-Malys E. Olanzapine in the treatment of agitation in hospitalized patients with schizophrenia and schizoaffective and schizofreniform disorders.  Med Sci Monit. 2004;  10 PI74-80
  • 38 WHO .ICD-10: The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva: World Health Organisation (WHO) 1992
  • 39 Wright P, Meehan K, Birkett M, Lindborg SR, Taylor CC, Morris P. et al . A comparison of the efficacy and safety of olanzapine versus haloperidol during transition from intramuscular to oral therapy.  Clin Ther. 2003;  25 1420-1428

1 These authors made equal contributions to the paper.

Correspondence

PD Dr. med. M. Lambert

Psychosis Early Detection and Intervention Centre (PEDIC)

Centre for Psychosocial Medicine

Department of Psychiatry and Psychotherapy

University Medical Centre Hamburg-Eppendorf

Martinistr. 52

20246 Hamburg

Germany

Phone: 49/40/428 03 76 70

Fax: +49/40/428 03 54 55

Email: lambert@uke.uni-hamburg.de

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