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Augmentation of clozapine with amisulpride: an effective therapeutic strategy for violent treatment-resistant schizophrenia patients in a UK high-security hospital

Published online by Cambridge University Press:  28 November 2013

James E. Hotham ,
Patrick J. D. Simpson ,
Rosalie S. Brooman-White ,
Amlan Basu ,
Callum C. Ross ,
Sharon A. Humphreys ,
Fintan Larkin ,
Nitin Gupta  and
Mrigendra Das
James E. Hotham
Affiliation:
Medical Sciences Division, John Radcliffe Hospital, University of Oxford, Oxford, UK
Patrick J. D. Simpson
Affiliation:
Medical Sciences Division, John Radcliffe Hospital, University of Oxford, Oxford, UK
Rosalie S. Brooman-White
Affiliation:
Medical Sciences Division, John Radcliffe Hospital, University of Oxford, Oxford, UK
Amlan Basu
Affiliation:
Broadmoor High Secure Hospital, West London Mental Health NHS Trust, London, UK Institute of Psychiatry, King's College, London, UK
Callum C. Ross
Affiliation:
Broadmoor High Secure Hospital, West London Mental Health NHS Trust, London, UK
Sharon A. Humphreys
Affiliation:
Broadmoor High Secure Hospital, West London Mental Health NHS Trust, London, UK
Fintan Larkin
Affiliation:
Broadmoor High Secure Hospital, West London Mental Health NHS Trust, London, UK
Nitin Gupta
Affiliation:
Department of Psychiatry, Government Medical College & Hospital, Chandigarh, India
Mrigendra Das*
Affiliation:
Broadmoor High Secure Hospital, West London Mental Health NHS Trust, London, UK School of Psychiatry, Oxford Deanery, Oxford, UK
*
*Address for correspondence: Mrigendra Das, Broadmoor Hospital, Crowthorne, Berkshire, RG45 7EG, UK. (Email: [email protected])
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Abstract

Objective

Clozapine is used in the management of treatment-resistant schizophrenia and is effective in reducing aggression; however a subgroup of patients is poorly responsive. For violent patients in this group, there is limited literature on the use of strategies to augment clozapine with other agents. Here we present a case series of 6 schizophrenia patients, within a high-security hospital, who have a history of serious violence and who were treated with clozapine augmented with amisulpride.

Methods

We reviewed case notes and health records for evidence of violence/aggression and positive factors such as engagement in activities, and Clinical Global Impression (CGI) scores were formulated. We also examined metabolic parameters before and after augmentation.

Results

All 6 of the patients showed clinical improvement in symptoms and a reduction in their risk of violence to others. Five patients had a reduction in number of violent/aggressive incidents, and all patients showed improvement in engagement in occupational, vocational, and/or psychological work. Metabolic parameters were largely unchanged except for 1 patient whose Body Mass Index (BMI) increased. Five patients reported side effects as unchanged or improved.

Conclusion

These schizophrenia patients with a history of violence showed clinical improvement and reduced aggression and violence with amisulpride augmentation of clozapine. To our knowledge, this is the first report of an antiaggressive benefit of this combination in forensic psychiatric patients. Further studies are warranted to establish the efficacy and anti-aggressive effects of amisulpride augmentation of clozapine.

Keywords

clozapineamisulprideaugmentationschizophreniaviolenceforensic
Type
Original Research
Information
CNS Spectrums , Volume 19 , Issue 5 , October 2014 , pp. 403 - 410
Copyright
Copyright © Cambridge University Press 2013 

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References

1. Fakra, E, Azorin, JM. Clozapine for the treatment of schizophrenia. Expert Opin Pharmacother. 2012; 13(13): 1923–1935.Google Scholar
2. 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): 789–796.Google Scholar
3. Rosenheck, R, Cramer, J, Xu, W, etal. A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. N Engl J Med. 1997; 337(12): 809–815.Google Scholar
4. Baldessarini, RJ, Frankenburg, FR. Clozapine—a novel antipsychotic agent. N Engl J Med. 1991; 324(11): 746–754.Google Scholar
5. Porcelli, S, Balzarro, B, Serretti, A. Clozapine resistance: augmentation strategies. Eur Neuropsychopharmacol. 2012; 22(3): 165–182.CrossRefGoogle ScholarPubMed
6. Stahl, SM. Antipsychotic polypharmacy, part 1: therapeutic option or dirty little secret? J Clin Psychiatry. 1999; 60(7): 425–426.Google Scholar
7. Stahl, SM. Antipsychotic polypharmacy: evidence based or eminence based? Acta Psychiatr Scand. 2002; 106(5): 321–322.Google Scholar
8. Stahl, SM. Antipsychotic polypharmacy: never say never, but never say always. Acta Psychiatr Scand. 2012; 125(5): 349–351.Google Scholar
9. Stahl, SM. Emerging guidelines for the use of antipsychotic polypharmacy. Rev Psiquiatr Salud Ment. 2013; 6(3): 97–100.CrossRefGoogle ScholarPubMed
10. Pai, NB, Laidlaw, M, Vella, SC. Augmentation of clozapine with another pharmacological agent: treatment for refractory schizophrenia in the “real world. ” Acta Psychiatr Scand. 2012; 126(1): 40–46.CrossRefGoogle ScholarPubMed
11. Zink, M, Englisch, S, Meyer-Lindenberg, A. Polypharmacy in schizophrenia. Curr Opin Psychiatry. 2010; 23(2): 103–111.CrossRefGoogle ScholarPubMed
12. Correll, CU, Rummel-Kluge, C, Corves, C, etal. Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. Schizophr Bull. 2009; 35(2): 443–457.CrossRefGoogle ScholarPubMed
13. Buchanan, RW, Kirkpatrick, B, Bryant, N, etal. Fluoxetine augmentation of clozapine treatment in patients with schizophrenia. Am J Psychiatry. 1996; 153(12): 1625–1627.Google Scholar
14. Wetzel, H, Anghelescu, I, Szegedi, A, etal. Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors: differential effects of fluvoxamine and paroxetine in a prospective study. J Clin Psychopharmacol. 1998; 18(1): 2–9.Google Scholar
15. Berk, M, Gama, CS, Sundram, S, etal. Mirtazapine add-on therapy in the treatment of schizophrenia with atypical antipsychotics: a double-blind, randomised, placebo-controlled clinical trial. Hum Psychopharmacol. 2009; 24(3): 233–238.CrossRefGoogle ScholarPubMed
16. Zoccali, R, Muscatello, MR, Cedro, C, etal. The effect of mirtazapine augmentation of clozapine in the treatment of negative symptoms of schizophrenia: a double-blind, placebo-controlled study. Int Clin Psychopharmacol. 2004; 19(2): 71–76.Google Scholar
17. Tiihonen, J, Hallikainen, T, Ryynänen, OP, etal. Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial. Biol Psychiatry. 2003; 54(11): 1241–1248.CrossRefGoogle ScholarPubMed
18. Goff, DC, Keefe, R, Citrome, L, etal. Lamotrigine as add-on therapy in schizophrenia: results of 2 placebo-controlled trials. J Clin Psychopharmacol. 2007; 27(6): 582–589.CrossRefGoogle ScholarPubMed
19. Muscatello, MR, Bruno, A, Pandolfo, G, etal. Topiramate augmentation of clozapine in schizophrenia: a double-blind, placebo-controlled study. J Psychopharmacol. 2011; 25(5): 667–674.Google Scholar
20. Small, JG, Klapper, MH, Malloy, FW, Steadman, TM. Tolerability and efficacy of clozapine combined with lithium in schizophrenia and schizoaffective disorder. J Clin Psychopharmacol. 2003; 23(3): 223–228.CrossRefGoogle ScholarPubMed
21. Evins, AE, Fitzgerald, SM, Wine, L, etal. Placebo-controlled trial of glycine added to clozapine in schizophrenia. Am J Psychiatry. 2000; 157(5): 826–828.Google Scholar
22. Heresco-Levy, U, Javitt, DC, Ermilov, M, etal. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry. 1999; 56(1): 29–36.Google Scholar
23. Assion, HJ, Reinbold, H, Lemanski, S, etal. Amisulpride augmentation in patients with schizophrenia partially responsive or unresponsive to clozapine: a randomized, double-blind, placebo-controlled trial. Pharmacopsychiatry. 2008; 41(1): 24–28.Google Scholar
24. Shiloh, R, Zemishlany, Z, Aizenberg, D, etal. Sulpiride augmentation in people with schizophrenia partially responsive to clozapine: a double-blind, placebo-controlled study. Br J Psychiatry. 1997; 171: 569–573.Google Scholar
25. Munro, J, Matthiasson, P, Osborne, S, etal. Amisulpride augmentation of clozapine: an open non-randomized study in patients with schizophrenia partially responsive to clozapine. Acta Psychiatr Scand. 2004; 110(4): 292–298.CrossRefGoogle ScholarPubMed
26. Zink, M, Knopf, U, Henn, FA, Thome, J. Combination of clozapine and amisulpride in treatment-resistant schizophrenia—case reports and review of the literature. Pharmacopsychiatry. 2004; 37(1): 26–31.Google Scholar
27. Kämpf, P, Agelink, MW, Naber, D. Augmentation of clozapine with amisulpride: a promising therapeutic approach to refractory schizophrenic symptoms. Pharmacopsychiatry. 2005; 38(1): 39–40.Google Scholar
28. Walsh, E, Buchanan, A, Fahy, T. Violence and schizophrenia: examining the evidence. Br J Psychiatry. 2002; 180: 490–495.Google Scholar
29. Wessely, S. The Camberwell Study of Crime and Schizophrenia. Soc Psychiatry Psychiatr Epidemiol. 1998; 33(Suppl 1): S24–S28.Google Scholar
30. Taylor, PJ, Estroff, SE. Schizophrenia and violence. In: Hirsch FR, Weinberger DR, eds. Schizophrenia, 2nd ed. Oxford, UK: Blackwell Science Ltd.; 2007; 30: 591–612.Google Scholar
31. Citrome, L, Volavka, J, Czobor, P, etal. Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia. Psychiatric Services. 2001; 52(11): 1510–1514.Google Scholar
32. Krakowski, MI, Czobor, P, Citrome, L, etal. Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry. 2006; 63(6): 622–629.CrossRefGoogle ScholarPubMed
33. 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): 1351–1371.CrossRefGoogle ScholarPubMed
34. Guy, W. The Clinical Global Impression Scale. In: Guy W, ed. ECDEU Assessment Manual for Psychopharmacology, –Rev ed Rockville, MD: US Deptartment of Health, Education and Welfare, ADAMHA, MIMH Psychopharmacology Research Branch; 1976: 218–222.Google Scholar
35. Webster, C, Douglas, K, Eaves, D, Hart, S. HCR-20: Assessing Risk for Violence. Version 2. Burnaby, BC, Canada: Mental Health, Law and Policy Institute, Simon Fraser University.Google Scholar
36. Genç, Y, Taner, E, Candansayar, S. Comparison of clozapine-amisulpride and clozapine-quetiapine combinations for patients with schizophrenia who are partially responsive to clozapine: a single-blind randomized study. Adv Ther. 2007; 24(1): 1–13.CrossRefGoogle ScholarPubMed
37. Ziegenbein, M, Sieberer, M, Kuenzel, HE, Kropp, S. Augmentation of clozapine with amisulpride in patients with treatment-resistant schizophrenia: an open clinical study. German Journal of Psychiatry. 2006; 9(1): 17–21.Google Scholar
38. Zink, M, Kuwilsky, A, Krumm, B, Dressing, H. Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomised controlled clinical trial. J Psychopharmacol. 2009; 23(3): 305–314.Google Scholar
39. Kuwilsky, A, Krumm, B, Englisch, S, etal. Long-term efficacy and tolerability of clozapine combined with ziprasidone or risperidone. Pharmacopsychiatry. 2010; 43(6): 216–220.CrossRefGoogle ScholarPubMed
40. Taylor, DM, Smith, L. Augmentation of clozapine with a second antipsychotic—a meta-analysis of randomized, placebo-controlled studies. Acta Psychiatr Scand. 2009; 119(6): 419–425.Google Scholar
41. Chang, JS, Ahn, YM, Park, HJ, etal. Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2008; 69(5): 720–731.Google Scholar
42. Sommer, IE, Begemann, MJ, Temmerman, A, Leucht, S. Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review. Schizophr Bull. 2012; 38(5): 1003–1011.CrossRefGoogle ScholarPubMed
43. 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): 337–372.CrossRefGoogle ScholarPubMed
44. Leucht, S. Amisulpride a selective dopamine antagonist and atypical antipsychotic: results of a meta-analysis of randomized controlled trials. Int J Neuropsychopharmacol. 2004; 7(Suppl 1): S15–S20.Google Scholar
45. Scatton, B, Claustre, Y, Cudennec, A, etal. Amisulpride: from animal pharmacology to therapeutic action. Int Clin Psychopharmacol. 1997; 12(Suppl 2): S29–S36.Google Scholar
46. Vernaleken, I, Siessmeier, T, Buchholz, HG, etal. High striatal occupancy of D2-like dopamine receptors by amisulpride in the brain of patients with schizophrenia. Int J Neuropsychopharmacol. 2004; 7(4): 421–430.Google Scholar
47. Abbas, AI, Hedlund, PB, Huang, XP, etal. Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo. Psychopharmacology (Berl). 2009; 205(1): 119–128.CrossRefGoogle ScholarPubMed
48. Perrault, G, Depoortere, R, Morel, E, etal. Psychopharmacological profile of amisulpride: an antipsychotic drug with presynaptic D2/D3 dopamine receptor antagonist activity and limbic selectivity. J Pharmacol Exp Ther. 1997; 280(1): 73–82.Google Scholar
49. Bowskill, SV, Patel, MX, Handley, SA, Flanagan, RJ. Plasma amisulpride in relation to prescribed dose, clozapine augmentation, and other factors: data from a therapeutic drug monitoring service, 2002–2010. Hum Psychopharmacol. 2012; 27(5): 507–513.Google Scholar
50. Nordström, AL, Farde, L, Halldin, C. High 5-HT2 receptor occupancy in clozapine treated patients demonstrated by PET. Psychopharmacology (Berl). 1993; 110(3): 365–367.Google Scholar
51. Kapur, S, Zipursky, RB, Remington, G. Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia. Am J Psychiatry. 1999; 156(2): 286–293.Google Scholar
52. Buckley, P, Bartell, J, Donenwirth, K, etal. Violence and schizophrenia: clozapine as a specific antiaggressive agent. Bull Am Acad Psychiatry Law. 1995; 23(4): 607–611.Google Scholar
53. Wilson, WH. Clinical review of clozapine treatment in a state hospital. Hosp Community Psychiatry. 1992; 43(7): 700–703.Google ScholarPubMed
54. Umukoro, S, Aladeokin, AC, Eduviere, AT. Aggressive behavior: a comprehensive review of its neurochemical mechanisms and management. Aggression and Violent Behavior. 2013; 18(2): 195–203.Google Scholar
55. Nelson, RJ, Trainor, BC. Neural mechanisms of aggression. Nat Rev Neurosci. 2007; 8(7): 536–546.Google Scholar
56. Lieberman, JA, Safferman, AZ, Pollack, S, etal. Clinical effects of clozapine in chronic schizophrenia: response to treatment and predictors of outcome. Am J Psychiatry. 1994; 151(12): 1744–1752.Google ScholarPubMed
57. Fabrazzo, M, La Pia, S, Monteleone, P, etal. Is the time course of clozapine response correlated to the time course of clozapine plasma levels?. A one-year prospective study in drug-resistant patients with schizophrenia. Neuropsychopharmacology. 2002; 27(6): 1050–1055.CrossRefGoogle Scholar
58. Schulte, PF. What is an adequate trial with clozapine? Clin Pharmacokinet. 2003; 42(7): 607–618.Google Scholar
59. Wilson, WH. Time required for initial improvement during clozapine treatment of refractory schizophrenia. American J Psychiatry. 1996; 157(7): 951–952.Google Scholar
60. Junginger, J, Parks-Levy, J, McGuire, L. Delusions and symptom-consistent violence. Psychiatr Serv. 1998; 49(2): 218–220.Google Scholar
61. 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.Google Scholar
62. Volavka, J, Zito, JM, Vitrai, J, Czobor, P. Clozapine effects on hostility and aggression in schizophrenia. J Clin Psychopharmacol. 1993; 13(4): 287–288.CrossRefGoogle ScholarPubMed
63. Krakowski, MI, Czobor, P. Executive function predicts response to antiaggression treatment in schizophrenia: a randomized controlled trial. J Clin Psychiatry. 2012; 73(1): 74–80.Google Scholar
64. Volavka, J, Citrome, L. Atypical antipsychotics in the treatment of the persistently aggressive psychotic patient: methodological concerns. Schizophr Res. 1999; 35(Suppl): S23–S33.Google Scholar
65. McGlashan, TH. A selective review of recent North American long-term followup studies of schizophrenia. Schizophr Bull. 1988; 14(4): 515–542.Google Scholar
66. Revicki, DA, Luce, BR, Weschler, JM, Brown, RE, Adler, MA. Cost effectiveness of clozapine for treatment-resistant schizophrenic patients. Hosp Community Psychiatry. 1990; 41(8): 850–854.Google ScholarPubMed