Psychiatric Quarterly

, Volume 89, Issue 1, pp 157–168 | Cite as

Clozapine in Reducing Aggression and Violence in Forensic Populations

  • Kathleen Patchan
  • Gopal Vyas
  • Ann L. Hackman
  • Marie Mackowick
  • Charles M. Richardson
  • Raymond C. Love
  • Ikwunga Wonodi
  • MacKenzie A. Sayer
  • Matthew Glassman
  • Stephanie Feldman
  • Deanna L. Kelly
Review Article


Popular media often portray people with a mental illness as being aggressive, violent, and incarcerated as a result of their behavior. Despite exaggeration in the media, risks for some aggressive behaviors are in fact higher in individuals with schizophrenia. This is often the case with influence of comorbid substance use disorders. It is essential that mental health professionals are aware of treatments that may help with attenuating and treating behaviors that contribute to violence, aggression and incarceration. This paper reviews violence and incarceration in individuals with schizophrenia as well as recommendations, guidelines and benefits for the use of clozapine in this population. Clozapine remains one of the most underutilized evidence-based medications available in the psychiatric arena in the United States. It is a viable and recommended option in the forensic population and it may be helpful on the path to recovery as well as bring substantial savings to the criminal justice system.


Clozapine Forensic Violence Aggression Criminal justice 



This work was supported in part by grants NIMH R01 MH102215 (Kelly PI) and R01 MH105571-01 (Kelly PI).

Compliance with Ethical Standards

This work was supported in part by grants NIMH R01 MH102215 (Kelly PI) and R01 MH105571–01 (Kelly PI).

Disclosure of Potential Conflicts of Interest

Dr. Raymond Love owns stock in GlaxoSmithKline. All other authors declare that they have no conflict of interest.

Research Involving Human Participants and/or Animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Bortolato, B, Miskowiak, KW, Kohler, CA, et al. Cognitive dysfunction in bipolar disorder and schizophrenia: a systematic review of meta-analyses. Neuropsychiatr Dis Treat 2015;11:3111–3125.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Carbon, M and Correll, CU. Thinking and acting beyond the positive: the role of the cognitive and negative symptoms in schizophrenia. CNS Spectr 2014;19 Suppl 1:38–52; quiz 35–37, 53.PubMedGoogle Scholar
  3. 3.
    Lysaker, PH, Vohs, J, Minor, KS, et al. Metacognitive Deficits in Schizophrenia: Presence and Associations With Psychosocial Outcomes. J Nerv Ment Dis 2015;203:530–536.CrossRefPubMedGoogle Scholar
  4. 4.
    Bouwmans, C, de Sonneville, C, Mulder, CL, et al. Employment and the associated impact on quality of life in people diagnosed with schizophrenia. Neuropsychiatr Dis Treat 2015;11:2125–2142.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Brekke, JS, Prindle, C, Bae, SW, et al. Risks for individuals with schizophrenia who are living in the community. Psychiatr Serv 2001;52:1358–1366.CrossRefPubMedGoogle Scholar
  6. 6.
    Latalova, K, Kamaradova, D, and Prasko, J. Violent victimization of adult patients with severe mental illness: a systematic review. Neuropsychiatr Dis Treat 2014;10:1925–1939.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Fazel, S, Gulati, G, Linsell, L, et al. Schizophrenia and violence: systematic review and meta-analysis. PLoS Med 2009;6:e1000120.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Regier, DA, Farmer, ME, Rae, DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA 1990;264:2511–2518.CrossRefPubMedGoogle Scholar
  9. 9.
    Mueser, KT, Penn, DL, Addington, J, et al. The NAVIGATE Program for First-Episode Psychosis: Rationale, Overview, and Description of Psychosocial Components. Psychiatr Serv 2015;66:680–690.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Dixon, LB, Goldman, HH, Bennett, ME, et al. Implementing Coordinated Specialty Care for Early Psychosis: The RAISE Connection Program. Psychiatr Serv 2015;66:691–698.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Miami-Dade County Criminal Mental Health Project. [cited 2016 9/7]; Available from:
  12. 12.
    Weinstein, H, Kim, D, Mack, A, et al. Prevalence and assessment of mental disorders in correctional settings. Handbook of correctional mental health 2005;43–68.Google Scholar
  13. 13.
    James, D and Glaze, L. Mental health problems of prison and jail inmates (Bureau of Justice Statistics Special Report, NCJ 213600). Washington, DC: Department of Justice 2006;Google Scholar
  14. 14.
    Soyka, M, Morhart-Klute, V, and Schoech, H. Delinquency and criminal offenses in former schizophrenic inpatients 7–12 years following discharge. Eur Arch Psychiatry Clin Neurosci 2004;254:289–294.CrossRefPubMedGoogle Scholar
  15. 15.
    Ghoreishi, A, Kabootvand, S, Zangani, E, et al. Prevalence and attributes of criminality in patients with schizophrenia. J Inj Violence Res 2015;7:7–12.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Ascher-Svanum, H, Nyhuis, AW, Faries, DE, et al. Involvement in the US criminal justice system and cost implications for persons treated for schizophrenia. BMC Psychiatry 2010;10:11.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Greenberg, G, Rosenheck, RA, Erickson, SK, et al. Criminal justice system involvement among people with schizophrenia. Community Ment Health J 2011;47:727–736.CrossRefPubMedGoogle Scholar
  18. 18.
    Baillargeon, J, Binswanger, IA, Penn, JV, et al. Psychiatric disorders and repeat incarcerations: the revolving prison door. Am J Psychiatry 2009;166:103–109.CrossRefPubMedGoogle Scholar
  19. 19.
    Steadman, HJ, Osher, FC, Robbins, PC, et al. Prevalence of serious mental illness among jail inmates. Psychiatr Serv 2009;60:761–765.CrossRefPubMedGoogle Scholar
  20. 20.
    Fazel, S and Danesh, J. Serious mental disorder in 23000 prisoners: a systematic review of 62 surveys. Lancet 2002;359:545–550.CrossRefPubMedGoogle Scholar
  21. 21.
    Hawthorne, WB, Folsom, DP, Sommerfeld, DH, et al. Incarceration among adults who are in the public mental health system: rates, risk factors, and short-term outcomes. Psychiatr Serv 2012;63:26–32.CrossRefPubMedGoogle Scholar
  22. 22.
    Lin, I, Muser, E, Munsell, M, et al. Economic impact of psychiatric relapse and recidivism among adults with schizophrenia recently released from incarceration: a Markov model analysis. J Med Econ 2015;18:219–229.CrossRefPubMedGoogle Scholar
  23. 23.
    Robertson, AG, Swanson, JW, Frisman, LK, et al. Patterns of justice involvement among adults with schizophrenia and bipolar disorder: key risk factors. Psychiatr Serv 2014;65:931–938.CrossRefPubMedGoogle Scholar
  24. 24.
    Robertson, AG, Swanson, JW, Lin, H, et al. Influence of Criminal Justice Involvement and Psychiatric Diagnoses on Treatment Costs Among Adults With Serious Mental Illness. Psychiatr Serv 2015;66:907–909.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Love, RC, Kelly, DL, Freudenreich, O, et al. Clozapine underutilization: Addressing the barriers. National Association of State Mental Health Porgram Directors 2016 [cited 2016 October 4]; Available from:
  26. 26.
    Kane, J, Honigfeld, G, Singer, J, et al. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988;45:789–796.CrossRefPubMedGoogle Scholar
  27. 27.
    Wahlbeck, K, Cheine, M, Essali, A, et al. Evidence of clozapine's effectiveness in schizophrenia: a systematic review and meta-analysis of randomized trials. Am J Psychiatry 1999;156:990–999.PubMedGoogle Scholar
  28. 28.
    Chakos, M, Lieberman, J, Hoffman, E, et al. Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials. Am J Psychiatry 2001;158:518–526.CrossRefPubMedGoogle Scholar
  29. 29.
    Tuunainen, A, Wahlbeck, K, and Gilbody, S. Newer atypical antipsychotic medication in comparison to clozapine: a systematic review of randomized trials. Schizophr Res 2002;56:1–10.CrossRefPubMedGoogle Scholar
  30. 30.
    Sinclair, D and Adams, CE. Treatment resistant schizophrenia: a comprehensive survey of randomised controlled trials. BMC Psychiatry 2014;14:253.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Citrome, L. A systematic review of meta-analyses of the efficacy of oral atypical antipsychotics for the treatment of adult patients with schizophrenia. Expert Opin Pharmacother 2012;13:1545–1573.CrossRefPubMedGoogle Scholar
  32. 32.
    Leucht, S, Cipriani, A, Spineli, L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013;382:951–962.CrossRefPubMedGoogle Scholar
  33. 33.
    Frogley, C, Taylor, D, Dickens, G, et al. A systematic review of the evidence of clozapine's anti-aggressive effects. Int J Neuropsychopharmacol 2012;15:1351–1371.CrossRefPubMedGoogle Scholar
  34. 34.
    Citrome, L, Volavka, J, Czobor, P, et al. Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia. Psychiatr Serv 2001;52:1510–1514.CrossRefPubMedGoogle Scholar
  35. 35.
    Volavka, J, Czobor, P, Sheitman, B, et al. Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder. Am J Psychiatry 2002;159:255–262.CrossRefPubMedGoogle Scholar
  36. 36.
    Krakowski, MI, Czobor, P, and Nolan, KA. Atypical antipsychotics, neurocognitive deficits, and aggression in schizophrenic patients. J Clin Psychopharmacol 2008;28:485–493.CrossRefPubMedGoogle Scholar
  37. 37.
    Victoroff, J, Coburn, K, Reeve, A, et al. Pharmacological management of persistent hostility and aggression in persons with schizophrenia spectrum disorders: a systematic review. J Neuropsychiatry Clin Neurosci 2014;26:283–312.CrossRefPubMedGoogle Scholar
  38. 38.
    Buchanan, RW, Kreyenbuhl, J, Kelly, DL, et al. The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull 2010;36:71–93.CrossRefPubMedGoogle Scholar
  39. 39.
    Stone-Brown, K, Naji, M, Francioni, A, et al. Psychotropic prescribing in seriously violent men with schizophrenia or personality disorder in a UK high security hospital. CNS Spectr 2016;21:60–69.CrossRefPubMedGoogle Scholar
  40. 40.
    Qurashi, I, Stephenson, P, Chu, S, et al. An evaluation of subjective experiences, effects and overall satisfaction with clozapine treatment in a UK forensic service. Ther Adv Psychopharmacol 2015;5:146–150.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Smith, H and White, T. The effect of clozapine on the social behaviour schedule in patients attending a forensic psychiatry day hospital. Med Sci Law 2004;44:213–216.CrossRefPubMedGoogle Scholar
  42. 42.
    Buscema, CA, Abbasi, QA, Barry, DJ, et al. An algorithm for the treatment of schizophrenia in the correctional setting: the Forensic Algorithm Project. J Clin Psychiatry 2000;61:767–783.CrossRefPubMedGoogle Scholar
  43. 43.
    Martin, A, O'Driscoll, C, and Samuels, A. Clozapine use in a forensic population in a New South Wales prison hospital. Aust N Z J Psychiatry 2008;42:141–146.CrossRefPubMedGoogle Scholar
  44. 44.
    Ronaldson, KJ, Fitzgerald, PB, and McNeil, JJ. Clozapine-induced myocarditis, a widely overlooked adverse reaction. Acta Psychiatr Scand 2015;132:231–240.CrossRefPubMedGoogle Scholar
  45. 45.
    Alawami, M, Wasywich, C, Cicovic, A, et al. A systematic review of clozapine induced cardiomyopathy. Int J Cardiol 2014;176:315–320.CrossRefPubMedGoogle Scholar
  46. 46.
    Williams, AM and Park, SH. Seizure associated with clozapine: incidence, etiology, and management. CNS Drugs 2015;29:101–111.CrossRefPubMedGoogle Scholar
  47. 47.
    Honigfeld, G, Arellano, F, Sethi, J, et al. Reducing clozapine-related morbidity and mortality: 5 years of experience with the Clozaril National Registry. J Clin Psychiatry 1998;59 Suppl 3:3–7.PubMedGoogle Scholar
  48. 48.
    Munro, J, O'Sullivan, D, Andrews, C, et al. Active monitoring of 12,760 clozapine recipients in the UK and Ireland. Beyond pharmacovigilance. The British Journal of Psychiatry 1999;175:576–580.CrossRefPubMedGoogle Scholar
  49. 49.
    Lahdelma, L and Appelberg, B. Clozapine-induced agranulocytosis in Finland, 1982-2007: long-term monitoring of patients is still warranted. J Clin Psychiatry 2012;73:837–842.CrossRefPubMedGoogle Scholar
  50. 50.
    Drew, L. Clozapine and agranulocytosis: re-assessing the risks. Australas Psychiatry 2013;21:335–337.CrossRefPubMedGoogle Scholar
  51. 51.
    Balda, MV, Garay, OU, Papale, RM, et al. Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012). Int Clin Psychopharmacol 2015;30:109–114.CrossRefPubMedGoogle Scholar
  52. 52.
    Ikai, S, Suzuki, T, Uchida, H, et al. Reintroduction of clozapine after perforation of the large intestine--a case report and review of the literature. Ann Pharmacother 2013;47:e31.CrossRefPubMedGoogle Scholar
  53. 53.
    Kelly, DL, Ben-Yoav, H, Payne, GF, et al. Blood Draw Barriers for Treatment with Clozapine and Development of Point-of-Care Monitoring Device. Clin Schizophr Relat Psychoses 2015;Google Scholar
  54. 54.
    Gee, S, Vergunst, F, Howes, O, et al. Practitioner attitudes to clozapine initiation. Acta Psychiatr Scand 2014;130:16–24.CrossRefPubMedGoogle Scholar
  55. 55.
    Tungaraza, TE and Farooq, S. Clozapine prescribing in the UK: views and experience of consultant psychiatrists. Ther Adv Psychopharmacol 2015;5:88–96.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    NC Division of Mental Health, Developmental Disabilities and Substance Abuse Services and the North Carolina Psychiatric Association. Clozapine (Clozaril): an underutilized evidence based treatment [PowerPoint Slides] (n.d.). Retrieved from
  57. 57.
    Hill, M and Freudenreich, O. Clozapine: key discussion points for prescribers. Clin Schizophr Relat Psychoses 2013;6:177–185.CrossRefPubMedGoogle Scholar
  58. 58.
    Citrome, L and Volavka, J. Pharmacological management of acute and persistent aggression in forensic psychiatry settings. CNS Drugs 2011;25:1009–1021.CrossRefPubMedGoogle Scholar
  59. 59.
    Kelly, DL, Dixon, LB, Kreyenbuhl, JA, et al. Clozapine utilization and outcomes by race in a public mental health system: 1994-2000. J Clin Psychiatry 2006;67:1404–1411.CrossRefPubMedGoogle Scholar
  60. 60.
    Mallinger, JB, Fisher, SG, Brown, T, et al. Racial disparities in the use of second-generation antipsychotics for the treatment of schizophrenia. Psychiatr Serv 2006;57:133–136.CrossRefPubMedGoogle Scholar
  61. 61.
    Copeland, LA, Zeber, JE, Valenstein, M, et al. Racial disparity in the use of atypical antipsychotic medications among veterans. Am J Psychiatry 2003;160:1817–1822.CrossRefPubMedGoogle Scholar
  62. 62.
    Kelly, DL, Kreyenbuhl, J, Dixon, L, et al. Clozapine underutilization and discontinuation in African Americans due to leucopenia. Schizophr Bull 2007;33:1221–1224.CrossRefPubMedGoogle Scholar
  63. 63.
    Moeller, FG, Chen, YW, Steinberg, JL, et al. Risk factors for clozapine discontinuation among 805 patients in the VA hospital system. Ann Clin Psychiatry 1995;7:167–173.CrossRefPubMedGoogle Scholar
  64. 64.
    Pai, NB and Vella, SC. Reason for clozapine cessation. Acta Psychiatr Scand 2012;125:39–44.CrossRefPubMedGoogle Scholar
  65. 65.
    Haddy, TB, Rana, SR, and Castro, O. Benign ethnic neutropenia: what is a normal absolute neutrophil count? J Lab Clin Med 1999;133:15–22.CrossRefPubMedGoogle Scholar
  66. 66.
    Denic, S, Showqi, S, Klein, C, et al. Prevalence, phenotype and inheritance of benign neutropenia in Arabs. BMC Blood Disord 2009;9:3.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Shoenfeld, Y, Alkan, ML, Asaly, A, et al. Benign familial leukopenia and neutropenia in different ethnic groups. Eur J Haematol 1988;41:273–277.CrossRefPubMedGoogle Scholar
  68. 68.
    Crosslin, DR, McDavid, A, Weston, N, et al. Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE Network. Hum Genet 2012;131:639–652.CrossRefPubMedGoogle Scholar
  69. 69.
    Paz, Z, Nails, M, and Ziv, E. The genetics of benign neutropenia. Isr Med Assoc J 2011;13:625–629.PubMedGoogle Scholar
  70. 70.
    Nalls, MA, Wilson, JG, Patterson, NJ, et al. Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart studies. Am J Hum Genet 2008;82:81–87.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Abecasis, GR, Altshuler, D, Auton, A, et al. A map of human genome variation from population-scale sequencing. Nature 2010;467:1061–1073.CrossRefPubMedGoogle Scholar
  72. 72.
    Reich, D, Nalls, MA, Kao, WH, et al. Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene. PLoS Genet 2009;5:e1000360.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Thobakgale, CF and Ndung'u, T. Neutrophil counts in persons of African origin. Curr Opin Hematol 2014;21:50–57.CrossRefPubMedGoogle Scholar
  74. 74.
    Patchan, KM, Richardson, C, Vyas, G, et al. The risk of suicide after clozapine discontinuation: Cause for concern. Ann Clin Psychiatry 2015;27:253–256.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Buchanan, RW. Clozapine: efficacy and safety. Schizophr Bull 1995;21:579–591.CrossRefPubMedGoogle Scholar
  76. 76.
    Borison, RL, Diamond, BI, Sinha, D, et al. Clozapine withdrawal rebound psychosis. Psychopharmacol Bull 1988;24:260–263.PubMedGoogle Scholar
  77. 77.
    Shiovitz, TM, Welke, TL, Tigel, PD, et al. Cholinergic rebound and rapid onset psychosis following abrupt clozapine withdrawal. Schizophr Bull 1996;22:591–595.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Kathleen Patchan
    • 1
  • Gopal Vyas
    • 2
  • Ann L. Hackman
    • 1
  • Marie Mackowick
    • 3
  • Charles M. Richardson
    • 2
  • Raymond C. Love
    • 4
  • Ikwunga Wonodi
    • 5
  • MacKenzie A. Sayer
    • 5
  • Matthew Glassman
    • 5
  • Stephanie Feldman
    • 5
  • Deanna L. Kelly
    • 5
  1. 1.Department of PsychiatryUniversity of Maryland School of MedicineBaltimoreUSA
  2. 2.Spring Grove Hospital and Maryland Psychiatric Research CenterUniversity of Maryland School of MedicineBaltimoreUSA
  3. 3.Clifton T. Perkins Hospital CenterJessupUSA
  4. 4.School of PharmacyUniversity of MarylandBaltimoreUSA
  5. 5.Maryland Psychiatric Research CenterUniversity of Maryland School of MedicineBaltimoreUSA

Personalised recommendations