Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-23T09:10:01.391Z Has data issue: false hasContentIssue false
  • English
  • Français

Treating the violent patient with psychosis or impulsivity utilizing antipsychotic polypharmacy and high-dose monotherapy

Published online by Cambridge University Press:  14 August 2014

Debbi A. Morrissette  and
Stephen M. Stahl
Debbi A. Morrissette
Affiliation:
Neuroscience Education Institute, Carlsbad, CA, USA Department of Biology, Palomar College, San Marcos, CA, USA
Stephen M. Stahl*
Affiliation:
Neuroscience Education Institute, Carlsbad, CA, USA Department of Psychiatry, University of California, San Diego, USA Department of Psychiatry, University of Cambridge, UK California Department of State Hospitals
*
*Address for Correspondence: Stephen M. Stahl, 1930 Palomar Point Way, Suite 103, Carlsbad, CA 92002, USA. (E-mail: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Insufficient treatment of psychosis often manifests as violent and aggressive behaviors that are dangerous to the patient and others, and that warrant treatment strategies which are not considered first-line, evidence-based practices. Such treatment strategies include both antipsychotic polypharmacy (simultaneous use of 2 antipsychotics) and high-dose antipsychotic monotherapy. Here we discuss the hypothesized neurobiological substrates of various types of violence and aggression, as well as providing arguments for the use of antipsychotic polypharmacy and high-dose monotherapy to target dysfunctional neurocircuitry in the subpopulation of patients that is treatment-resistant, violent, and aggressive. In this review, we focus primarily on the data supporting the use of second-generation, atypical antipsychotics both at high doses and in combination with other antipsychotics.

Keywords

atypicalpolypharmacyviolencemonotherapyaggressiontreatment-resistant
Type
Review Articles
Information
CNS Spectrums , Volume 19 , Issue 5 , October 2014 , pp. 439 - 448
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.)

References

1. Stahl, SM, Morrissette, DA, Citrome, L, et al. “Meta-guidelines” for the management of patients with schizophrenia. CNS Spectr. 2013; 18(3): 150–162.Google Scholar
2. Stahl, SM. Emerging guidelines for the use of antipsychotic polypharmacy. Rev Psiquiatr Salud Ment. 2013; 6(3): 97–100.Google Scholar
3. Citrome, L, Volavka, J. Pharmacological management of acute and persistent aggression in forensic psychiatry settings. CNS Drugs. 2011; 25(12): 1009–1021.Google Scholar
4. Warburton, K. The new mission of forensic mental health systems: managing violence as a medical syndrome in an environment that balances treatment and safety. CNS Spectr. In press.Google Scholar
5. Nolan, KA, Czobor, P, Roy, BB, et al. Characteristics of assaultive behavior among psychiatric inpatients. Psychiatr Serv. 2003; 54(7): 1012–1016.Google Scholar
6. Volavka, J, Citrome, L. Heterogeneity of violence in schizophrenia and implications for long-term treatment. Int J Clin Pract. 2008; 62(8): 1237–1245.Google Scholar
7. Volavka, J, Citrome, L. Pathways to aggression in schizophrenia affect results of treatment. Schizophr Bull. 2011; 37(5): 921–929.CrossRefGoogle ScholarPubMed
8. Swanson, JW, Swartz, MS, Van Dorn, RA, et al. Comparison of antipsychotic medication effects on reducing violence in people with schizophrenia. Br J Psychiatry. 2008; 193(1): 37–43.CrossRefGoogle ScholarPubMed
9. Quanbeck, CD, McDermott, BE, Lam, J, Eisenstark, H, Sokolov, G, Scott, CL. Categorization of aggressive acts committed by chronically assaultive state hospital patients. Psychiatr Serv. 2007; 58(4): 521–528.CrossRefGoogle ScholarPubMed
10. Stahl, SM. Stahl's Essential Psychopharmacology, 4th ed. New York: Cambridge University Press; 2013.Google Scholar
11. Stahl, SM, Morrissette, DA. Stahl's Illustrated Violence: Neural Circuits, Genetics, and Treatment. New York: Cambridge University Press; 2014.CrossRefGoogle Scholar
12. Siever, LJ. Neurobiology of aggression and violence. Am J Psychiatry. 2008; 165(4): 429–442.Google Scholar
13. 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
14. Coccaro, EF, McCloskey, MS, Fitzgerald, DA, Phan, KL. Amygdala and orbitofrontal reactivity to social threat in individuals with impulsive aggression. Biol Psychiatry. 2007; 62(2): 168–178.CrossRefGoogle ScholarPubMed
15. Coccaro, EF, Sripada, CS, Yanowitch, RN, Phan, KL. Corticolimbic function in impulsive aggressive behavior. Biol Psychiatry. 2011; 69(12): 1153–1159.Google Scholar
16. Bobes, J, Fillat, O, Arango, C. Violence among schizophrenia out-patients compliant with medication: prevalence and associated factors. Acta Psychiatr Scand. 2009; 119(3): 218–225.Google Scholar
17. Meyer, J. A rational approach to employing high plasma levels of antipsychotics for violence associated with schizophrenia: case vignettes. CNS Spectr. In press. DOI: http://dx.doi.org/10.1017/S1092852914000236.Google Scholar
18. Stahl, SM. Antipsychotic polypharmacy: never say never, but never say always. Acta Psychiatr Scand. 2012; 125(5): 349–351.Google Scholar
19. Pavlov, KA, Chistiakov, DA, Chekhonin, VP. Genetic determinants of aggression and impulsivity in humans. J Appl Genet. 2012; 53(1): 61–82.Google Scholar
20. Fazel, S, Grann, M, Langstrom, N. What is the role of epidemiology for forensic psychiatry? Crim Behav Ment Health. 2009; 19(5): 281–285.Google Scholar
21. Fazel, S, Gulati, G, Linsell, L, Geddes, JR, Grann, M. Schizophrenia and violence: systematic review and meta-analysis. PLoS Med. 2009; 6(8): e1000120.Google Scholar
22. Fazel, S, Langstrom, N, Hjern, A, Grann, M, Lichtenstein, P. Schizophrenia, substance abuse, and violent crime. JAMA. 2009; 301(19): 2016–2023.Google Scholar
23. Topiwala, A, Fazel, S. The pharmacological management of violence in schizophrenia: a structured review. Expert Rev Neurother. 2011; 11(1): 53–63.Google Scholar
24. 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.CrossRefGoogle ScholarPubMed
25. Krakowski, MI, Czobor, P, Nolan, KA. Atypical antipsychotics, neurocognitive deficits, and aggression in schizophrenic patients. J Clin Psychopharmacol. 2008; 28(5): 485–493.CrossRefGoogle ScholarPubMed
26. Singh, JP, Grann, M, Fazel, S. A comparative study of violence risk assessment tools: a systematic review and metaregression analysis of 68 studies involving 25,980 participants. Clin Psychol Rev. 2011; 31(3): 499–513.Google Scholar
27. Song, H, Min, SK. Aggressive behavior model in schizophrenic patients. Psychiatry Res. 2009; 167(1–2): 58–65.Google Scholar
28. Uchida, H, Takeuchi, H, Graff-Guerrero, A, Suzuki, T, Watanabe, K, Mamo, DC. Dopamine D2 receptor occupancy and clinical effects: a systematic review and pooled analysis. J Clin Psychopharmacol. 2011; 31(4): 497–502.Google Scholar
29. Correll, CU. From receptor pharmacology to improved outcomes: individualising the selection, dosing, and switching of antipsychotics. Eur Psychiatry. 2010; 25(Suppl 2): S12–S21.Google Scholar
30. Nord, M, Farde, L. Antipsychotic occupancy of dopamine receptors in schizophrenia. CNS Neurosci Ther. 2011; 17(2): 97–103.Google Scholar
31. Uchida, H, Takeuchi, H, Graff-Guerrero, A, Suzuki, T, Watanabe, K, Mamo, DC. Predicting dopamine D receptor occupancy from plasma levels of antipsychotic drugs: a systematic review and pooled analysis. J Clin Psychopharmacol. 2011; 31(3): 318–325.Google Scholar
32. Stauffer, V, Case, M, Kollack-Walker, S, et al. Trajectories of response to treatment with atypical antipsychotic medication in patients with schizophrenia pooled from 6 double-blind, randomized clinical trials. Schizophr Res. 2011; 130(1–3): 11–19.Google Scholar
33. Robinson, DG, Woerner, MG, Alvir, JM, et al. Predictors of treatment response from a first episode of schizophrenia or schizoaffective disorder. Am J Psychiatry. 1999; 156(4): 544–549.Google Scholar
34. Stahl, SM. Stahl's Essential Psychopharmacology, 3rd ed. New York: Cambridge University Press; 2008.Google Scholar
35. Morrissette, DA, Stahl, SM. Optimizing outcomes in schizophrenia: long-acting depots and long-term treatment. CNS Spectr. 2012; 17(Suppl 1): 10–21.Google Scholar
36. Ritsner, MS, ed. Polypharmacy in Psychiatric Practice, Volume I: Multiple Medication Use Strategies. New York: Springer Verlag; 2013.Google Scholar
37. Ritsner, MS, ed. Polypharmacy in Psychiatric Practice, Volume II: Use of Polypharmacy in the "Real World". New York: Springer Verlag; 2013.Google Scholar
38. Stentebjerg-Olesen, M, Jeppesen, P, Pagsberg, AK, et al. Early nonresponse determined by the Clinical Global Impressions scale predicts poorer outcomes in youth with schizophrenia spectrum disorders naturalistically treated with second-generation antipsychotics. J Child Adolesc Psychopharmacol. 2013; 23(10): 665–675.Google Scholar
39. Mauri, MC, Volonteri, LS, Colasanti, A, Fiorentini, A, De Gaspari, IF, Bareggi, SR. Clinical pharmacokinetics of atypical antipsychotics: a critical review of the relationship between plasma concentrations and clinical response. Clin Pharmacokinet. 2007; 46(5): 359–388.Google Scholar
40. Remington, G, Kapur, S. Antipsychotic dosing: how much but also how often? Schizophr Bull. 2010; 36(5): 900–903.CrossRefGoogle ScholarPubMed
41. Samaha, AN, Seeman, P, Stewart, J, Rajabi, H, Kapur, S. “Breakthrough” dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time. J Neurosci. 2007; 27(11): 2979–2986.Google Scholar
42. Seeman, P. Dopamine D2 receptors as treatment targets in schizophrenia. Clin Schizophr Relat Psychoses. 2010; 4(1): 56–73.Google Scholar
43. Davis, JM, Chen, N. Dose response and dose equivalence of antipsychotics. J Clin Psychopharmacol. 2004; 24(2): 192–208.CrossRefGoogle ScholarPubMed
44. Krakowski, MI, Kunz, M, Czobor, P, Volavka, J. Long-term high-dose neuroleptic treatment: who gets it and why? Hosp Community Psychiatry. 1993; 44(7): 640–644.Google Scholar
45. Gisev, N, Bell, JS, Chen, TF. Factors associated with antipsychotic polypharmacy and high-dose antipsychotics among individuals receiving compulsory treatment in the community. J Clin Psychopharmacol. 2014; 34(3): 307–312.Google Scholar
46. Roh, D, Chang, JG, Kim, CH, Cho, HS, An, SK, Jung, YC. Antipsychotic polypharmacy and high-dose prescription in schizophrenia: a 5-year comparison. Aust N Z J Psychiatry. 2014; 48(1): 52–60.Google Scholar
47. Barnes, TR, Paton, C. Antipsychotic polypharmacy in schizophrenia: benefits and risks. CNS Drugs. 2011; 25(5): 383–399.Google Scholar
48. Fleischhacker, WW, Uchida, H. Critical review of antipsychotic polypharmacy in the treatment of schizophrenia. Int J Neuropsychopharmacol. 2014; 17(7): 1083–1093.Google Scholar
49. Fujita, J, Nishida, A, Sakata, M, Noda, T, Ito, H. Excessive dosing and polypharmacy of antipsychotics caused by pro re nata in agitated patients with schizophrenia. Psychiatry Clin Neurosci. 2013; 67(5): 345–351.Google Scholar
50. Gallego, JA, Bonetti, J, Zhang, J, Kane, JM, Correll, CU. Prevalence and correlates of antipsychotic polypharmacy: a systematic review and meta-regression of global and regional trends from the 1970s to 2009. Schizophr Res. 2012; 138(1): 18–28.Google Scholar
51. Lochmann van Bennekom, MWH, Gijsman, HJ, Zitman, FG. Antipsychotic polypharmacy in psychotic disorders: a critical review of neurobiology, efficacy, tolerability and cost effectiveness. J Psychopharmacol. 2013; 27(4): 327–336.Google Scholar
52. Sagud, M, Vuksan-Cusa, B, Zivkovic, M, et al. Antipsychotics: to combine or not to combine? Psychiatr Danub. 2013; 25(3): 306–310.Google Scholar
53. Suokas, JT, Suvisaari, JM, Haukka, J, Korhonen, P, Tiihonen, J. Description of long-term polypharmacy among schizophrenia outpatients. Soc Psychiatry Psychiatr Epidemiol. 2013; 48(4): 631–638.Google Scholar
54. Freudenreich, O, Goff, DC. Antipsychotic combination therapy in schizophrenia: a review of efficacy and risks of current combinations. Acta Psychiatr Scand. 2002; 106(5): 323–330.Google Scholar
55. Goren, JL, Meterko, M, Williams, S, et al. Antipsychotic prescribing pathways, polypharmacy, and clozapine use in treatment of schizophrenia. Psychiatr Serv. 2013; 64(6): 527–533.CrossRefGoogle ScholarPubMed
56. Englisch, S, Zink, M. Treatment-resistant schizophrenia: evidence-based strategies. Mens Sana Monogr. 2012; 10(1): 20–32.Google ScholarPubMed
57. Langle, G, Steinert, T, Weiser, P, et al. Effects of polypharmacy on outcome in patients with schizophrenia in routine psychiatric treatment. Acta Psychiatr Scand. 2012; 125(5): 372–381.Google Scholar
58. Essock, SM, Schooler, NR, Stroup, TS, et al. Effectiveness of switching from antipsychotic polypharmacy to monotherapy. Am J Psychiatry. 2011; 168(7): 702–708.Google Scholar
59. Stahl, SM, Grady, MM. A critical review of atypical antipsychotic utilization: comparing monotherapy with polypharmacy and augmentation. Curr Med Chem. 2004; 11(3): 313–327.Google Scholar
60. Stahl, SM. Focus on antipsychotic polypharmacy: evidence-based prescribing or prescribing-based evidence? Int J Neuropsychopharmacol. 2004; 7(2): 113–116.Google Scholar
61. Stahl, SM. Antipsychotic polypharmacy: evidence based or eminence based? Acta Psychiatr Scand. 2002; 106(5): 321–322.Google Scholar
62. Stahl, SM. Antipsychotic polypharmacy: squandering precious resources? J Clin Psychiatry. 2002; 63(2): 93–94.Google Scholar
63. Stahl, SM. Antipsychotic polypharmacy, part 2: tips on use and misuse. J Clin Psychiatry. 1999; 60(8): 506–507.Google Scholar
64. Stahl, SM. Antipsychotic polypharmacy, part 1: therapeutic option or dirty little secret? J Clin Psychiatry. 1999; 60(7): 425–426.CrossRefGoogle ScholarPubMed
65. Stahl, SM. “Awakening” from schizophrenia: intramolecular polypharmacy and the atypical antipsychotics. J Clin Psychiatry. 1997; 58(9): 381–382.Google Scholar
66. Suzuki, T, Uchida, H, Tanaka, KF, et al. Revising polypharmacy to a single antipsychotic regimen for patients with chronic schizophrenia. Int J Neuropsychopharmacol. 2004; 7(2): 133–142.Google Scholar
67. Correll, CU, Rummel-Kluge, C, Corves, C, Kane, JM, Leucht, S. Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. Schizophr Bull. 2009; 35(2): 443–457.Google Scholar
68. Iasevoli, F, Buonaguro, EF, Marconi, M, et al. Efficacy and clinical determinants of antipsychotic polypharmacy in psychotic patients experiencing an acute relapse and admitted to hospital stay: results from a cross-sectional and a subsequent longitudinal pilot study. ISRN Pharmacology. 2014; 2014: 762127.CrossRefGoogle Scholar
69. Coccaro, EF. Intermittent explosive disorder as a disorder of impulsive aggression for DSM-5. Am J Psychiatry. 2012; 169(6): 577–588.CrossRefGoogle ScholarPubMed
70. Rosell, DR, Thompson, JL, Slifstein, M, et al. Increased serotonin 2A receptor availability in the orbitofrontal cortex of physically aggressive personality disordered patients. Biol Psychiatry. 2010; 67(12): 1154–1162.Google Scholar
71. Winstanley, CA, Theobald, DE, Dalley, JW, Glennon, JC, Robbins, TW. 5-HT2A and 5-HT2C receptor antagonists have opposing effects on a measure of impulsivity: interactions with global 5-HT depletion. Psychopharmacology (Berl). 2004; 176(3–4): 376–385.Google Scholar
72. Englisch, S, Zink, M. Combined antipsychotic treatment involving clozapine and aripiprazole. Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32(6): 1386–1392.Google Scholar
73. Katona, L, Czobor, P. Bitter I. Real-world effectiveness of antipsychotic monotherapy vs. polypharmacy in schizophrenia: to switch or to combine? A nationwide study in Hungary. Schizophr Res. 2014; 152(1): 246–254.Google Scholar
74. Ballon, J, Stroup, TS. Polypharmacy for schizophrenia. Curr Opin Psychiatry. 2013; 26(2): 208–213.Google Scholar
75. Fleischhacker, WW, Heikkinen, ME, Olie, JP, et al. Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial. Int J Neuropsychopharmacol. 2010; 13(8): 1115–1125.CrossRefGoogle ScholarPubMed
76. Chang, JS, Ahn, YM, Park, HJ, et al. 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
77. Thompson, C. The use of high-dose antipsychotic medication. Br J Psychiatry. 1994; 164(4): 448–458.Google Scholar
78. Schwartz, TL, Stahl, SM. Treatment strategies for dosing the second generation antipsychotics. CNS Neurosci Ther. 2011; 17(2): 110–117.Google Scholar
79. Volavka, J, Czobor, P, Nolan, K, et al. Overt aggression and psychotic symptoms in patients with schizophrenia treated with clozapine, olanzapine, risperidone, or haloperidol. J Clin Psychopharmacol. 2004; 24(2): 225–228.Google Scholar
80. Kantrowitz, JT, Citrome, L. Lurasidone for schizophrenia: what's different? Expert Rev Neurother. 2012; 12(3): 265–273.Google Scholar
81. Aggarwal, NK, Sernyak, MJ, Rosenheck, RA. Prevalence of concomitant oral antipsychotic drug use among patients treated with long-acting, intramuscular, antipsychotic medications. J Clin Psychopharmacol. 2012; 32(3): 323–328.Google Scholar
82. Elie, D, Poirier, M, Chianetta, J, Durand, M, Gregoire, C, Grignon, S. Cognitive effects of antipsychotic dosage and polypharmacy: a study with the BACS in patients with schizophrenia and schizoaffective disorder. J Psychopharmacol. 2010; 24(7): 1037–1044.Google Scholar
83. Hiemke, C, Baumann, P, Bergemann, N, et al. AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011. Pharmacopsychiatry. 2011; 44(6): 195–235.Google Scholar
84. Potkin, SG, Keator, DB, Kesler-West, ML, et al. D2 receptor occupancy following lurasidone treatment in patients with schizophrenia or schizoaffective disorder. CNS Spectr. 2014; 19(2): 176–181.Google Scholar