Skip to main content
×
×
Home

Clozapine: an effective treatment for seriously violent and psychopathic men with antisocial personality disorder in a UK high-security hospital

  • Darcy Brown (a1), Fintan Larkin (a2), Samrat Sengupta (a2), Jose L. Romero-Ureclay (a2), Callum C. Ross (a2), Nitin Gupta (a3), Morris Vinestock (a2) and Mrigendra Das (a2)...
Abstract
Objective

A number of studies have demonstrated the anti-aggressive properties of clozapine in schizophrenia and its positive effect in borderline personality disorder. There is no published literature on the treatment of antisocial personality disorder (ASPD) with clozapine. We present a case series of 7 patients with primary ASPD and high psychopathic traits treated with clozapine, having a significant history of serious violence and currently detained in a UK based high-security hospital.

Methods

A retrospective review of case notes was carried out to formulate Clinical Global Impression (CGI) scores and record incidents of violence and aggression. Effect on specific symptom domains (cognitive-perceptual, impulsive-behavioural dyscontrol, affective dysregulation) was also noted. Metabolic parameters and serum clozapine levels were also sampled.

Results

All 7 patients showed significant improvement on clozapine. It was shown to benefit all symptom domains, especially impulsive behavioral dyscontrol and anger. The number of violent incidents committed by 6 of the 7 patients reduced significantly, and all patients’ risk of violence reduced. Clozapine serum levels for 6 of the 7 patients were in the range 150–350 ng/mL.

Conclusion

Clozapine is of benefit in reducing the clinical severity of ASPD. It improved all symptom domains, especially impulsive-behavioral dyscontrol and anger, and reduced levels of aggression and violence, especially at lower doses (serum levels <350 ng/m). To our knowledge, this is the first account of clozapine treatment in patients with ASPD and high psychopathy.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Clozapine: an effective treatment for seriously violent and psychopathic men with antisocial personality disorder in a UK high-security hospital
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Clozapine: an effective treatment for seriously violent and psychopathic men with antisocial personality disorder in a UK high-security hospital
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Clozapine: an effective treatment for seriously violent and psychopathic men with antisocial personality disorder in a UK high-security hospital
      Available formats
      ×
Copyright
The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence . The written permission of Cambridge University Press must be obtained for commercial re-use.
Corresponding author
*Address for correspondence: Mrigendra Das, Broadmoor Hospital, Crowthorne, Berkshire, RG45 7EG, UK. (Email: mrigendra.das@wlmht.nhs.uk)
Footnotes
Hide All

We wish to thank John Wakelam and Stephen Heslop (pharmacists at Broadmoor Hospital) and Ottilie Sedgwick (research psychologist at Broadmoor Hospital) for their assistance in accessing records.

Footnotes
References
Hide All
1. Ingenhoven, T, Lafay, P, Rinne, T, etal. Effectiveness of pharmacotherapy for severe personality disorders: meta-analyses of randomized controlled trials. J Clin Psychiatry. 2010; 71(1): 1425.
2. Lieb, K, Völlm, B, Rücker, G, etal. Pharmacotherapy for borderline personality disorder: Cochrane systematic review of randomised trials. Br J Psychiatry. 2010; 196(1): 412.
3. Stoffers, JBA, Völlm, G, Rücker, A, etal. Pharmacological interventions for borderline personality disorder. Cochrane Database Syst Rev. 2010; (6): CD005653.
4. Bellino, S, Paradiso, E, Bogetto, F. Efficacy and tolerability of quetiapine in the treatment of borderline personality disorder: a pilot study. J Clin Psychiatry. 2006; 67(7): 10421046.
5. Hilger, E, Barnas, C, Kasper, S. Quetiapine in the treatment of borderline personality disorder. World J Biol Psychiatry. 2003; 4(1): 4244.
6. Villeneuve, E, Lemelin, S. Open-label study of atypical neuroleptic quetiapine for treatment of borderline personality disorder: impulsivity as main target. J Clin Psychiatry. 2005; 66(10): 12981303.
7. Nickel, M, Muehlbacher, M, Nickel, C, etal. Aripiprazole in the treatment of patients with borderline personality disorder: a double-blind, placebo-controlled study. Am J Psychiatry. 2006; 163(5): 833838.
8. Bellino, S, Bozzatello, P, Rinaldi, C, Bogetto, F. Paliperidone ER in the treatment of borderline personality disorder: a pilot study of efficacy and tolerability. Depress Res Treat. 2011; 2011: 680194.
9. Grootens, KP, Verkes, RJ. Emerging evidence for the use of atypical antipsychotics in borderline personality disorder. Pharmacopsychiatry. 2005; 38(01): 2023.
10. Bogenschutz, MP, Nurnberg, G. Olanzapine versus placebo in the treatment of borderline personality disorder. J Clin Psychiatry. 2004; 65(1): 104109.
11. Linehan, MM, McDavid, JD, Brown, MZ, Sayrs, JH, Gallop, RJ. Olanzapine plus dialectical behavior therapy for women with high irritability who meet criteria for borderline personality disorder: a double-blind, placebo-controlled pilot study. J Clin Psychiatry. 2008; 69(6): 9991005.
12. Schulz, CS, Camlin, KL, Berry, SA, Jesberger, JA. Olanzapine safety and efficacy in patients with borderline personality disorder and co-morbid dysthymia. Biol Psychiatry. 1999; 46(10): 14291435.
13. Zanarini, MC, Frankenburg, FR, Parachini, EA. A preliminary, randomized trial of fluoxetine, olanzapine, and the olanzapine-fluoxetine combination in women with borderline personality disorder. J Clin Psychiatry. 2004; 65(7): 903907.
14. Zanarini, MC, Frankenburg, FR. Olanzapine treatment of female borderline personality disorder patients: a double-blind, placebo-controlled pilot study. J Clin Psychiatry. 2001; 62(11): 849854.
15. Keshavan, M, Shad, M, Soloff, P, Schooler, N. Efficacy and tolerability of olanzapine in the treatment of schizotypal personality disorder. Schizophr Res. 2004; 71(1): 97101.
16. Koenigsberg, HW, Reynolds, D, Goodman, M, etal. Risperidone in the treatment of schizotypal personality disorder. J Clin Psychiatry. 2003; 64(6): 628634.
17. Rocca, P, Marchiaro, L, Cocuzza, E, Bogetto, F. Treatment of borderline personality disorder with risperidone. J Clin Psychiatry. 2002; 63(3): 241244.
18. Vauquelin, G, Bostoen, S, Vanderheyden, P, Seeman, P. Clozapine, atypical antipsychotics, and the benefits of fast-off D2 dopamine receptor antagonism. Naunyn Schmiedebergs Arch Pharmacol. 2012; 385(4): 337372.
19. Fakra, E, Azorin, J. Clozapine for the treatment of schizophrenia. Expert Opin Pharmacother. 2012; 13(3): 19231935.
20. Chakos, M, Lieberman, J, Hoffman, E, Bradford, D, Sheitman, B. Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials. Am J Psychiatry. 2001; 158(4): 518526.
21. Kane, J, Honigfeld, G, Singer, J, Meltzer, H. Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988; 45(9): 789796.
22. Meltzer, , Herbert, Y. Treatment-resistant schizophrenia-the role of clozapine. Curr Med Res Opin. 1997; 14(1): 120.
23. Chengappa, KN, Ebeling, T, Kang, JS, Levine, J, Parepally, H. Clozapine reduces severe self-mutilation and aggression in psychotic patients with borderline personality disorder. J Clin Psychiatry. 1999; 60(7): 477484.
24. Vohra, AK. Treatment of severe borderline personality disorder with clozapine. Indian J Psychiatry. 2010; 52(3): 267269.
25. Benedetti, F, Sforzini, L, Colombo, C, Maffei, C, Smeraldi, E. Low-dose clozapine in acute and continuation treatment of severe borderline personality disorder. J Clin Psychiatry. 1998; 59(3): 103107.
26. Swinton, M. Clozapine in severe borderline personality disorder. The Journal of Forensic Psychiatry. 2001; 12(3): 580591.
27. Frankenburg, FR, Zanarini, MC. Clozapine treatment of borderline patients: a preliminary study. Compr Psychiatry. 1993; 34(6): 402405.
28. Buckley, P, Bartell, J, Donenwirth, K, etal. Violence and schizophrenia: clozapine as a specific antiaggressive agent. Bull Am Acad Psychiatry Law. 1995; 23(4): 607611.
29. Frogley, C, Taylor, D, Dickens, G, Picchioni, M. A systematic review of the evidence of clozapine's anti-aggressive effects. Int J Neuropsychopharmacol. 2012; 15(9): 13511371.
30. Chengappa, KNR, Vasile, J, Levine, J, etal. Clozapine: its impact on aggressive behaviour among patients in a state psychiatric hospital. Schizophr Res. 2002; 53(1–2): 16.
31. 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): 15101514.
32. Dalal, B, Larkin, E, Leese, M, Taylor, PJ. Clozapine treatment of long-standing schizophrenia and serious violence: a two-year follow-up study of the first 50 patients treated with clozapine in Rampton high security hospital. Crim Behav Ment Health. 1999; 9(2): 168178.
33. Rabinowitz, J, Avnon, M, Rosenberg, V. Effect of clozapine on physical and verbal aggression. Schizophr Res. 1996; 22(3): 249255.
34. Ratey, JJ, Leveroni, C, Kilmer, D, Gutheil, C. The effects of clozapine on severely aggressive psychiatric inpatients in a state hospital. J Clin Psychiatry. 1993; 54(6): 219223.
35. Volavka, J. The effects of clozapine on aggression and substance abuse in schizophrenic patients. J Clin Psychiatry. 1999; 60(Suppl 12): 4346.
36. 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): 622629.
37. Hare, RD. Manual for the Revised Psychopathy Checklist (1st ed.). 1991. Toronto, ON, Canada: Multi-Health Systems. URL for other refs: http://scholar.google.co.uk/scholar?hl=en&q=hare+checklist&btnG=&as_sdt=1%2C5&as_sdtp=
38. Hart, SD, Cox, DN, Hare, RD. The Hare Psychopathy Checklist: Screening Version (PCL: SV). Multi-Health Systems, Inc.; 1995. Again book (1st ed). Toronto, ON, Canada.
39. Guy, W. The Clinical Global Impression Scale. In: Guy W, ed. ECDEU Assessment Manual for Psychopharmacology. Rev ed. Rockville, MD: U.S. Department of Health, Education and Welfare, ADAMHA, MIMH Psychopharmacology Research Branch; 1976:218–222.
40. Frankenburg, FR, Zanarini, MC. Clozapine treatment of borderline patients: a preliminary study. Compr Psychiatry. 1993; 34(6): 402405.
41. Binks, CA, Fenton, M, McCarthy, L, etal. Psychological therapies for people with borderline personality disorder. Cochrane Database Syst Rev. 2006; (1): CD005652.
42. Soloff, PH. Algorithms for pharmacological treatment of personality dimensions: symptom-specific treatments for cognitive-perceptual, affective, and impulsive-behavioural dysregulation. Bull Menninger Clin. 1997; 62(2): 195214.
43. Webster, C, Douglas, K, Eaves, D, Hart, S. HCR-20: Assessing Risk for Violence. Version 2; 1992. Burnaby, BC, Canada: Mental Health, Law and Policy Institute, Simon Fraser University.
44. World Health Organization. The ICD-10 Classification of Mental and Behavioral Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva: World Health Organization; 1992; 50.
45. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000.
46. Glazer, GM, Dickson, RA. Clozapine reduces violence and persistent aggression in schizophrenia. J Clin Psychiatry. 1998; 59(Suppl 3): 814.
47. Spina, E, Avenoso, A, Facciolà, G, etal. Relationship between plasma concentrations of clozapine and norclozapine and therapeutic response in patients with schizophrenia resistant to conventional neuroleptics. Psychopharmacology (Berl). 2000; 148(1): 8389.
48. Humbert-Claude, M, Davenas, E, Gbahou, F, Vincent, L, Arrang, JM. Involvement of histamine receptors in the atypical antipsychotic profile of clozapine: a reassessment in vitro and in vivo. Psychopharmacology (Berl). 2012; 220(1): 225241.
49. Stahl, SM. Psychopharmacology of Antipsychotics. London: Martin Dunitz; 1999.
50. Harrison, AA, Everitt, BJ, Robbins, TW. Central 5-HT depletion enhances impulsive responding without affecting the accuracy of attentional performance: interactions with dopaminergic mechanisms. Psychopharmacology (Berl). 1997; 133(4): 329342.
51. Vukhac, K, Sankoorika, EL, Yanyan, Wang. Dopamine D2L receptor-and age-related reduction in offensive aggression. Neuroreport. 2001; 12(5): 10351038.
52. Wade, TR, Wit, HD, Richards, JB. Effects of dopaminergic drugs on delayed reward as a measure of impulsive behaviour in rats. Psychopharmacology (Berl). 2000; 150(1): 90101.
53. Chotai, J, Kullgren, J, Åsberg, M. CSF monoamine metabolites in relation to the diagnostic interview for borderline patients (DIB). Neuropsychobiology. 1998; 38(4): 207212.
54. Coccaro, EF, Silk, KR, ed. Neurotransmitter function in personality disorders. In: Biology of Personality Disorders. Washington, DC: American Psychiatric Press; 1998: 125.
55. Friedel, RO. Dopamine dysfunction in borderline personality disorder: a hypothesis. Neuropsychopharmacology. 2004; 29(6): 10291039.
56. Adams, DB. Brain mechanisms for offence, defence, and submission. Behav Brain Sci. 1979; 2(2): 201213.
57. Berman, ME, Tracy, JI, Coccaro, EF. The serotonin hypothesis of aggression revisited. Clin Psychol Rev. 1997; 17(6): 651665.
58. Brown, GL. Aggression, suicide, and serotonin: relationships of CSF amine metabolites. Am J Psychiatry. 1982; 139(6): 741746.
59. de Boer, FS, Koolhaas, JM. 5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis. Eur J Pharmacol. 2005; 526(1–3): 125139.
60. Gowin, JL, Swann, AC, Moeller, FG, Lane, SD. Zolmitriptan and human aggression: interaction with alcohol. Psychopharmacology (Berl). 2010; 210(4): 521531.
61. Miczek, KA, Fish, EW, Joseph, F, De Almeida, RM. Social and neural determinants of aggressive behaviour: pharmacotherapeutic targets at serotonin, dopamine and γ-aminobutyric acid systems. Psychopharmacology (Berl). 2002; 163(3): 434458.
62. Moss, HB, Yao, JK, Panzak, GL. Serotonergic responsivity and behavioral dimensions in antisocial personality disorder with substance abuse. Biol Psychiatry. 1990; 28(4): 325338.
63. Constantino, JN, Morris, JA, Murphy, DL. CSF 5-HIAA and family history of antisocial personality disorder in newborns. Am J Psychiatry. 1997; 154(2): 17711773.
64. Krakowski, M. Violence and serotonin: influence of impulse control, affect regulation, and social functioning. J Neuropsychiatry Clin Neurosci. 2003; 15(3): 294305.
65. Umukoro, S, Aladeokin, AC, Eduviere, AT. Aggressive behavior: a comprehensive review of its neurochemical mechanisms and management. Aggression and Violent Behavior. 2012; 18(2): 195203.
66. Paris, P. Antisocial and borderline personality disorders: two separate diagnoses or two aspects of the same psychopathology? Compr Psychiatry. 1997; 38(4): 237242.
67. Bateman, AW, Tyrer, P. Psychological treatment for personality disorders. Advances in Psychiatric Treatment. 2004; 10(5): 378388.
68. Bellino, S, Paradiso, E, Bogetto, F. Efficacy and tolerability of pharmacotherapies for borderline personality disorder. CNS Drugs. 2008; 22(8): 671692.
69. Nelson, KJ, Schulz, CS. Treatment advances in borderline personality disorder. Psychiatric Annals. 2012; 42(2): 5964.
70. Dolan, M. Psychopathic personality in young people. Advances in Psychiatric Treatment. 2004; 10(6): 466473.
71. Hare, RD. Psychopathy, affect and behaviour. In: Cooke DJ, Forth AE, Hare RD, eds. Psychopathy: Theory, Research and Implications for Society. Dordrecht, the Netherlands: Springer; 1998: 105137.
72. Salekin, RT, Rogers, R, Sewell, KW. A review and meta-analysis of the Psychopathy Checklist and Psychopathy Checklist-Revised: predictive validity of dangerousness. Clinical Psychology: Science and Practice. 1996; 3(3): 203215.
73. Buckholtz, JW, Treadway, MT, Cowan, RL, etal. Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits. Nat Neurosci. 2010; 13(4): 419421.
74. Dolan, MC, Anderson, IM. The relationship between serotonergic function and the Psychopathy Checklist: Screening Version. J Psychopharmacol. 2003; 17(2): 216222.
75. Soderstrom, H, Blennow, K, Sjodin, AK, Forsman, A. New evidence for an association between the CSF HVA:5-HIAA ratio and psychopathic traits. J Neurol Neurosurg Psychiatry. 2003; 74(7): 918921.
76. Barkataki, I, Kumar, V, Das, M, Taylor, P, Sharma, T. Volumetric structural brain abnormalities in men with schizophrenia or antisocial personality disorder. Behav Brain Res. 2006; 169(2): 239247.
77. Kumari, V, Das, M, Taylor, PJ, etal. Neural and behavioural responses to threat in men with a history of serious violence and schizophrenia or antisocial personality disorder. Schizoph Res. 2009; 110(1–3): 4758.
78. Yang, Y, Raine, R. Prefrontal structural and functional brain imaging findings in antisocial, violent, and psychopathic individuals: a meta-analysis. Psychiatry Res. 2009; 174(2): 8188.
79. Chopra, HD, Beatson, JA. Psychotic symptoms in borderline personality disorder. Am J Psychiatry. 1986; 143(12): 16051607.
80. Kendal, T, Pilling, S, Tyrer, P, etal. Guidelines: Borderline and Antisocial Personality Disorders: Summary of NICE Guidance. BMJ. 2009; 338(7689): 293295.
81. Volavka, J, Citrome, L. Atypical antipsychotics in the treatment of the persistently aggressive psychotic patient: methodological concerns. Schizophr Res. 1999; 35(Suppl): S23S33.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

CNS Spectrums
  • ISSN: 1092-8529
  • EISSN: 2165-6509
  • URL: /core/journals/cns-spectrums
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed