Hostname: page-component-7dd5485656-dk7s8 Total loading time: 0 Render date: 2025-10-30T18:24:50.585Z Has data issue: false hasContentIssue false
  • English
  • Français

The psychopharmacology of violence: making sensible decisions

Published online by Cambridge University Press:  26 February 2014

Leslie Citrome  and
Jan Volavka
Leslie Citrome*
Affiliation:
Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, New York, USA
Jan Volavka
Affiliation:
Department of Psychiatry, New York University School of Medicine, New York, New York, USA
*
*Address for correspondence: Leslie Citrome, MD, MPH, 11 Medical Park Drive, Suite 106, Pomona, NY 10970, USA. (Email: citrome@cnsconsultant.com)
Get access Rights & Permissions [Opens in a new window]

Abstract

Violent behavior associated with mental disorders is a common reason for admission to a psychiatric inpatient unit. Once hospitalized, patients may continue to be intermittently agitated and have persistent aggressive behaviors, preventing their discharge back into the community. Managing agitation quickly with effective pharmacological agents can avoid further escalation to aggression and violence. In the acute setting, this usually involves the parenteral use of antipsychotics, with or without benzodiazepines. Within the past decade, short-acting intramuscular formulations of second-generation antipsychotics have become available and provide a means to induce calm with a substantially lower risk of acute dystonia or akathisia compared with haloperidol. New alternative formulations that avoid injections include inhalation and sublingual administration. Longer-term management of persistent aggressive behavior by reducing the frequency and intensity of future episodes of agitation is more complex. In contrast to agitation associated with schizophrenia or bipolar mania, no agents have yet been approved by regulatory agencies for the treatment of persistent aggressive behavior. The strongest evidence supports the use of clozapine as an antihostility agent, followed by olanzapine. Adjunctive strategies with anticonvulsants and beta-adrenergic agents may also be worthwhile to consider.

Keywords

Agitationaggressionpsychosisschizophreniabipolar mania

Information

Type
Review Articles
Information
CNS Spectrums , Volume 19 , Issue 5 , October 2014 , pp. 411 - 418
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

1. Swift, RH, Harrigan, EP, Cappelleri, JC, Kramer, D, Chandler, LP. Validation of the behavioural activity rating scale (BARS): a novel measure of activity in agitated patients. J Psychiatr Res. 2002; 36(2): 87–95.CrossRefGoogle Scholar
2. Lindenmayer, JP, Brown, E, Baker, RW, etal. An excitement subscale of the Positive and Negative Syndrome Scale. Schizophr Res. 2004; 68(2–3): 331–337.CrossRefGoogle ScholarPubMed
3. Yudofsky, SC, Silver, JM, Jackson, W, Endicott, J, Williams, D. The Overt Aggression Scale for the objective rating of verbal and physical aggression. Am J Psychiatry. 1986; 143(1): 35–39.Google ScholarPubMed
4. Björkdahl, A, Olsson, D, Palmstierna, T. Nurses’ short-term prediction of violence in acute psychiatric intensive care. Acta Psychiatr Scand. 2006; 113(3): 224–229.CrossRefGoogle ScholarPubMed
5. Kay, SR, Opler, LA, Fiszbein, A. Positive and Negative Syndrome Scale Manual. North Tonawanda, NY: Multi-Health Systems; 2000.Google Scholar
6. Citrome, L, Green, L. The dangerous agitated patient: what to do right now. Postgrad Med. 1990; 87(2): 231–236.CrossRefGoogle Scholar
7. Citrome, L. Agitation III: pharmacologic treatment of agitation. In: Glick RL, Berlin JS, Fishkind A, Zeller S, eds. Emergency Psychiatry: Principles and Practice. Baltimore, MD: Lippincott Williams & Wilkins, Wolters Kluwer Health; 2008: 137–147.Google Scholar
8. Regier, DA, Farmer, ME, Rae, DS, etal. Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiologic Catchment Area (ECA) Study. JAMA. 1990; 264(19): 2511–2518.CrossRefGoogle ScholarPubMed
9. Battaglia, J, Moss, S, Rush, J, etal. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. Am J Emerg Med. 1997; 15(4): 335–340.CrossRefGoogle ScholarPubMed
10. Brook, S, Lucey, JV, Gunn, KP. Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis: Ziprasidone I.M. Study Group. J Clin Psychiatry. 2000; 61(12): 933–941.CrossRefGoogle ScholarPubMed
11. Daniel, DG, Zimbroff, DL, Swift, RH, Harrigan, EP. The tolerability of intramuscular ziprasidone and haloperidol treatment and the transition to oral therapy. Int Clin Psychopharmacol. 2004; 19(1): 9–15.CrossRefGoogle ScholarPubMed
12. Brook, S, Walden, J, Benattia, I, Siu, CO, Romano, SJ. Ziprasidone and haloperidol in the treatment of acute exacerbation of schizophrenia and schizoaffective disorder: comparison of intramuscular and oral formulations in a 6-week, randomized, blinded-assessment study. Psychopharmacology (Berl). 2005; 178(4): 514–523.CrossRefGoogle Scholar
13. Wright, P, Meehan, K, Birkett, M, etal. A comparison of the efficacy and safety of olanzapine versus haloperidol during transition from intramuscular to oral therapy. Clin Ther. 2003; 25(5): 1420–1428.CrossRefGoogle ScholarPubMed
14. Andrezina, R, Marcus, RN, Oren, DA, etal. Intramuscular aripiprazole or haloperidol and transition to oral therapy in patients with agitation associated with schizophrenia: sub-analysis of a double-blind study. Curr Med Res Opin. 2006; 22(11): 2209–2219.CrossRefGoogle ScholarPubMed
15. Lesem, MD, Zajecka, JM, Swift, RH, Reeves, KR, Harrigan, EP. Intramuscular ziprasidone, 2 mg versus 10 mg, in the short-term management of agitated psychotic patients. J Clin Psychiatry. 2001; 62(1): 12–18.CrossRefGoogle ScholarPubMed
16. Daniel, DG, Potkin, SG, Reeves, KR, Swift, RH, Harrigan, EP. Intramuscular (IM) ziprasidone 20 mg is effective in reducing acute agitation associated with psychosis: a double-blind, randomized trial. Psychopharmacology (Berl). 2001; 155(2): 128–134.CrossRefGoogle ScholarPubMed
17. Citrome, L. Comparison of intramuscular ziprasidone, olanzapine, or aripiprazole for agitation: a quantitative review of efficacy and safety. J Clin Psychiatry. 2007; 68(12): 1876–1885.CrossRefGoogle ScholarPubMed
18. Pfizer Inc. Geodon: US package insert for Geodon (ziprasidone HCl) capsules and Geodon (ziprasidone mesylate) injection for intramuscular use. September 2013. http://labeling.pfizer.com/ShowLabeling.aspx?id=584. Accessed December 2, 2013.Google Scholar
19. Wright, P, Birkett, M, David, SR, etal. Double-blind, placebo-controlled comparison of intramuscular olanzapine and intramuscular haloperidol in the treatment of acute agitation in schizophrenia. Am J Psychiatry. 2001; 158(7): 1149–1151.CrossRefGoogle ScholarPubMed
20. Breier, A, Meehan, K, Birkett, M, etal. 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(5): 441–448.CrossRefGoogle ScholarPubMed
21. Meehan, K, Zhang, F, David, S, etal. A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania. J Clin Psychopharmacol. 2001; 21(4): 389–397.CrossRefGoogle ScholarPubMed
22. Meehan, KM, Wang, H, David, SR, etal. Comparison of rapidly acting intramuscular olanzapine, lorazepam, and placebo: a double-blind, randomized study in acutely agitated patients with dementia. Neuropsychopharmacology. 2002; 26(4): 494–504.CrossRefGoogle ScholarPubMed
23. Andrezina, R, Josiassen, RC, Marcus, RN, etal. 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 (Berl). 2006; 188(3): 281–292.CrossRefGoogle ScholarPubMed
24. Tran-Johnson, TK, Sack, DA, Marcus, RN, etal. Efficacy and safety of intramuscular aripiprazole in patients with acute agitation: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2007; 68(1): 111–119.CrossRefGoogle ScholarPubMed
25. Zimbroff, DL, Marcus, RN, Manos, G, etal. Management of acute agitation in patients with bipolar disorder: efficacy and safety of intramuscular aripiprazole. J Clin Psychopharmacol. 2007; 27(2): 171–176.CrossRefGoogle ScholarPubMed
26. Rappaport, SA, Marcus, RN, Manos, G, McQuade, RD, Oren, DA. A randomized, double-blind, placebo-controlled tolerability study of intramuscular aripiprazole in acutely agitated patients with Alzheimer's, vascular, or mixed dementia. J Am Med Dir Assoc. 2009; 10(1): 21–27.CrossRefGoogle ScholarPubMed
27. Allen, MH, Feifel, D, Lesem, MD, etal. Efficacy and safety of loxapine for inhalation in the treatment of agitation in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011; 72(10): 1313–1321.CrossRefGoogle ScholarPubMed
28. Lesem, MD, Tran-Johnson, TK, Riesenberg, RA, etal. Rapid acute treatment of agitation in individuals with schizophrenia: multicentre, randomised, placebo-controlled study of inhaled loxapine. Br J Psychiatry. 2011; 198(1): 51–58.CrossRefGoogle ScholarPubMed
29. Kwentus, J, Riesenberg, RA, Marandi, M, etal. Rapid acute treatment of agitation in patients with bipolar I disorder: a multicenter, randomized, placebo-controlled clinical trial with inhaled loxapine. Bipolar Disord. 2012; 14(1): 31–40.CrossRefGoogle ScholarPubMed
30. Citrome, L. Inhaled loxapine for agitation revisited: focus on effect sizes from 2 Phase III randomised controlled trials in persons with schizophrenia or bipolar disorder. Int J Clin Pract. 2012; 66(3): 318–325.CrossRefGoogle ScholarPubMed
31. Citrome, L. Addressing the need for rapid treatment of agitation in schizophrenia and bipolar disorder: focus on inhaled loxapine as an alternative to injectable agents. Ther Clin Risk Manag. 2013; 9: 235–245.CrossRefGoogle ScholarPubMed
32. Merck & Co., Inc. Saphris: US package insert for Saphris (asenapine) sublingual tablets. March 2013. http://www.merck.com/product/usa/pi_circulars/s/saphris/saphris_pi.pdf. Accessed December 2, 2013.Google Scholar
33. Citrome, L. Asenapine for schizophrenia and bipolar disorder: a review of the efficacy and safety profile for this newly approved sublingually absorbed second-generation antipsychotic. Int J Clin Pract. 2009; 63(12): 1762–1784.CrossRefGoogle ScholarPubMed
34. Pratts M, Citrome L, Grant W, Leso L, Opler LA. A single-dose, randomized, double-blind, placebo-controlled trial of sublingual asenapine for acute agitation. Acta Psychiatrica Scand. In press.Google Scholar
35. Wilson, MP, Pepper, D, Currier, GW, Holloman, GH Jr, Feifel, D. The psychopharmacology of agitation: consensus statement of the American Association for Emergency Psychiatry Project Beta Psychopharmacology Workgroup. West J Emerg Med. 2012; 13(1): 26–34.CrossRefGoogle Scholar
36. Volavka, J, Citrome, L. Heterogeneity of violence in schizophrenia and implications for long-term treatment. Int J Clin Pract. 2008; 62(8): 1237–1245.CrossRefGoogle ScholarPubMed
37. Nolan, KA, Volavka, J, Czobor, P, etal. Aggression and psychopathology in treatment-resistant inpatients with schizophrenia and schizoaffective disorder. J Psychiatr Res. 2005; 39(1): 109–115.CrossRefGoogle ScholarPubMed
38. Nolan, KA, Volavka, J, Mohr, P, Czobor, P. Psychopathy and violent behavior among patients with schizophrenia or schizoaffective disorder. Psychiatr Serv. 1999; 50(6): 787–792.CrossRefGoogle ScholarPubMed
39. Cooke, DJ, Michie, C. Refining the construct of psychopathy: towards a hierarchical model. Psychol Assess. 2001; 13(2): 171–188.CrossRefGoogle ScholarPubMed
40. Nolan, KA, Czobor, P, Roy, BB, etal. Characteristics of assaultive behavior among psychiatric inpatients. Psychiatr Serv. 2003; 54(7): 1012–1016.CrossRefGoogle ScholarPubMed
41. Citrome, L. New second-generation long-acting injectable antipsychotics for the treatment of schizophrenia. Expert Rev Neurother. 2013; 13(7): 767–783.CrossRefGoogle ScholarPubMed
42. Volavka, J, Zito, JM, Vitrai, J, Czobor, P. Clozapine effects on hostility and aggression in schizophrenia. J Clin Psychopharmacol. 1993; 13(4): 287–289.CrossRefGoogle ScholarPubMed
43. Citrome, L, Volavka, J, Czobor, P, etal. Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia. Psychiatr Serv. 2001; 52(11): 1510–1514.CrossRefGoogle ScholarPubMed
44. Volavka, J, Czobor, P, Nolan, K, etal. Overt aggression and psychotic symptoms in patients with schizophrenia treated with clozapine, olanzapine, risperidone, or haloperidol. J Clin Psychopharmacol. 2004; 24(2): 225–228.CrossRefGoogle ScholarPubMed
45. 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(6): 622–629.CrossRefGoogle ScholarPubMed
46. Citrome, L. Clozapine for schizophrenia: life-threatening or life-saving treatment? Current Psychiatry. 2009; 8(12): 56–63.Google Scholar
47. Volavka, J, Czobor, P, Derks, EM, etal; EUFEST Study Group. Efficacy of antipsychotic drugs against hostility in the European First-Episode Schizophrenia Trial (EUFEST). J Clin Psychiatry. 2011; 72(7): 955–961.CrossRefGoogle ScholarPubMed
48. Volavka, J, Czobor, P, Citrome, L, Van Dorn, RA. Effectiveness of antipsychotic drugs against hostility in patients with schizophrenia in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. CNS Spectr. In press. DOI: http://dx.doi.org/10.1017/S1092852913000849 CrossRefGoogle Scholar
49. Kinon, BJ, Roychowdhury, SM, Milton, DR, Hill, AL. Effective resolution with olanzapine of acute presentation of behavioral agitation and positive psychotic symptoms in schizophrenia. J Clin Psychiatry. 2001; 62(Suppl 2): 17–21.Google ScholarPubMed
50. Citrome, L, Volavka, J. Pharmacological management of acute and persistent aggression in forensic psychiatry settings. CNS Drugs. 2011; 25(12): 1009–1021.CrossRefGoogle ScholarPubMed
51. Citrome, L. Adjunctive lithium and anticonvulsants for the treatment of schizophrenia: what is the evidence? Expert Rev Neurother. 2009; 9(1): 55–71.CrossRefGoogle ScholarPubMed
52. Citrome, L, Levine, J, Allingham, B. Changes in use of valproate and other mood stabilizers for patients with schizophrenia from 1994 to 1998. Psychiatr Serv. 2000; 51(5): 634–638.CrossRefGoogle ScholarPubMed
53. Citrome, L, Shope, CB, Nolan, KA, Czobor, P, Volavka, J. Risperidone alone versus risperidone plus valproate in the treatment of patients with schizophrenia and hostility. Int Clin Psychopharmacol. 2007; 22(6): 356–362.CrossRefGoogle ScholarPubMed
54. Huband, N, Ferriter, M, Nathan, R, Jones, H. Antiepileptics for aggression and associated impulsivity. Cochrane Database Syst Rev. 2010;(2): CD003499.Google ScholarPubMed
55. Ratey, JJ, Sorgi, P, O'Driscoll, GA, etal. Nadolol to treat aggression and psychiatric symptomatology in chronic psychiatric inpatients: a double-blind, placebo-controlled study. J Clin Psychiatry. 1992; 53(2): 41–46.Google ScholarPubMed
56. Alpert, M, Allan, ER, Citrome, L, etal. A double-blind, placebo-controlled study of adjunctive nadolol in the management of violent psychiatric patients. Psychopharmacol Bull. 1990; 26(3): 367–371.Google ScholarPubMed
57. Caspi, N, Modai, I, Barak, P, etal. Pindolol augmentation in aggressive schizophrenic patients: a double-blind crossover randomized study. Int Clin Psychopharmacol. 2001; 16(2): 111–115.CrossRefGoogle ScholarPubMed