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Medication and aggressiveness in real-world schizophrenia. Results from the FACE-SZ dataset

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Abstract

Introduction

The primary objective of this study was to determine if second-generation antipsychotic (SGA) administration was associated with lower aggressiveness scores compared to first-generation (FGA) in schizophrenia (SZ). The secondary objective was to determine if antidepressants, mood stabilizers, and benzodiazepines administration were respectively associated with lower aggressiveness scores compared to patients who were not administered these medications.

Methods

Three hundred thirty-one patients with schizophrenia (N = 255) or schizoaffective disorder (N = 76) (mean age = 32.5 years, 75.5 % male gender) were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with the structured clinical interview for DSM-IV Axis I disorders and validated scales for psychotic symptomatology, insight, and compliance. Aggressiveness was measured by the Buss–Perry Aggression Questionnaire (BPAQ) score. Ongoing psychotropic treatment was recorded.

Results

Patients who received SGA had lower BPAQ scores than patients who did not (p = 0.01). More specifically, these patients had lower physical and verbal aggression scores. On the contrary, patients who received benzodiazepines had higher BPAQ scores than patients who did not (p = 0.04). No significant difference was found between BPAQ scores of patients respectively being administered mood stabilizers (including valproate), antidepressant, and the patients who were not. These results were found independently of socio-demographical variables, psychotic symptomatology, insight, compliance into treatment, daily-administered antipsychotic dose, the way of antipsychotic administration (oral vs long acting), current alcohol disorder, and daily cannabis consumption.

Conclusion

The results of the present study are in favor of the choice of SGA in SZ patients with aggressiveness, but these results need further investigation in longitudinal studies. Given the potent side effects of benzodiazepines (especially dependency and cognitive impairment) and the results of the present study, their long-term prescription is not recommended in patients with schizophrenia and aggressive behavior.

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References

  • Aleman A, Kahn RS (2001) Effects of the atypical antipsychotic risperidone on hostility and aggression in schizophrenia: a meta-analysis of controlled trials. Eur Neuropsychopharmacol 11:289–293

    Article  CAS  PubMed  Google Scholar 

  • Alia-Klein N, O’Rourke TM, Goldstein RZ, Malaspina D (2007) Insight into illness and adherence to psychotropic medications are separately associated with violence severity in a forensic sample. Aggress Behav 33:86–96. doi:10.1002/ab.20170

    Article  PubMed  Google Scholar 

  • Arango C, Bombín I, González-Salvador T, García-Cabeza I, Bobes J (2006) Randomised clinical trial comparing oral versus depot formulations of zuclopenthixol in patients with schizophrenia and previous violence. Eur Psychiatry 21:34–40. doi:10.1016/j.eurpsy.2005.07.006

    Article  CAS  PubMed  Google Scholar 

  • Bendel RB, Afifi AA (1977) Comparison of stopping rules in forward “stepwise” regression. J Am Stat Assoc 72:46. doi:10.2307/2286904

    Google Scholar 

  • Bitter I, Czobor P, Dossenbach M, Volavka J (2005) Effectiveness of clozapine, olanzapine, quetiapine, risperidone, and haloperidol monotherapy in reducing hostile and aggressive behavior in outpatients treated for schizophrenia: a prospective naturalistic study (IC-SOHO). Eur Psychiatry 20:403–408. doi:10.1016/j.eurpsy.2005.01.009

    Article  PubMed  Google Scholar 

  • Bursac Z, Gauss CH, Williams DK, Hosmer DW (2008) Purposeful selection of variables in logistic regression. Source Code Biol Med 3:17. doi:10.1186/1751-0473-3-17

    Article  PubMed Central  PubMed  Google Scholar 

  • Buss AH, Perry M (1992) The aggression questionnaire. J Pers Soc Psychol 63:452–459. doi:10.1037/0022-3514.63.3.452

    Article  CAS  PubMed  Google Scholar 

  • Cheung P, Schweitzer I, Crowley K, Tuckwell V (1997) Violence in schizophrenia: role of hallucinations and delusions. Schizophr Res 26:181–190

    Article  CAS  PubMed  Google Scholar 

  • Citrome L, Volavka J (2011) Pharmacological management of acute and persistent aggression in forensic psychiatry settings. CNS Drugs 25:1009–1021. doi:10.2165/11596930-000000000-00000

    Article  CAS  PubMed  Google Scholar 

  • Citrome L, Volavka J, Czobor P, Sheitman B, Lindenmayer JP, McEvoy J, Cooper TB, Chakos M, Lieberman JA (2001) Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia. Psychiatr Serv 52:1510–1514

    Article  CAS  PubMed  Google Scholar 

  • Fazel S, Wolf A, Palm C, Lichtenstein P (2014) Violent crime, suicide, and premature mortality in patients with schizophrenia and related disorders: a 38 years total population study in Sweden. Lancet Psychiatry 1:44–54. doi:10.1016/S2215-0366(14)70223-8

    Article  PubMed Central  PubMed  Google Scholar 

  • Foley SR, Kelly BD, Clarke M, McTigue O, Gervin M, Kamali M, Larkin C, O’Callaghan E, Browne S (2005) Incidence and clinical correlates of aggression and violence at presentation in patients with first episode psychosis. Schizophr Res 72:161–168. doi:10.1016/j.schres.2004.03.010

    Article  PubMed  Google Scholar 

  • Fond G, Guillaume S, Jaussent I, Beziat S, Macgregor A, Bernard P, Courtet P, Bailly D, Quantin X (2013) Prevalence and smoking behavior characteristics of nonselected smokers with childhood and/or adult self-reported ADHD symptoms in a smoking-cessation program: a cross-sectional study. J Atten Disord. doi:10.1177/1087054713497396

    PubMed  Google Scholar 

  • Fresán A, de la Fuente-Sandoval C, Juárez F, Loyzaga C, Meyenberg N, García-Anaya M, Nicolini H, Apiquian R (2005) [Sociodemographic features related to violent behavior in schizophrenia]. Actas Esp Psiquiatr 33:188–193

    PubMed  Google Scholar 

  • Gerevich J, Bácskai E, Czobor P (2007) The generalizability of the buss–perry aggression questionnaire. Int J Methods Psychiatr Res 16:124–136. doi:10.1002/mpr.221

    Article  PubMed  Google Scholar 

  • Gillies D, Sampson S, Beck A, Rathbone J (2013) Benzodiazepines for psychosis-induced aggression or agitation. Cochrane Database Syst Rev 4:CD003079. doi:10.1002/14651858.CD003079.pub3

    PubMed  Google Scholar 

  • Huband N, Ferriter M, Nathan R, Jones H (2010) Antiepileptics for aggression and associated impulsivity. Cochrane Database Syst Rev 17:CD003499. doi:10.1002/14651858.CD003499.pub3

    Google Scholar 

  • Ingenhoven T, Lafay P, Rinne T, Passchier J, Duivenvoorden H (2010) Effectiveness of pharmacotherapy for severe personality disorders: meta-analyses of randomized controlled trials. J Clin Psychiatry 71:14–25

    Article  CAS  PubMed  Google Scholar 

  • Krakowski M, Czobor P, Chou C-Y (1999) Course of violence in patients with schizophrenia: relationship to clinical symptoms. Schizophr Bull 25:505–517

    Article  CAS  PubMed  Google Scholar 

  • Krakowski MI, Czobor P, Nolan KA (2008) Atypical antipsychotics, neurocognitive deficits, and aggression in schizophrenic patients. J Clin Psychopharmacol 28:485–493. doi:10.1097/JCP.0b013e3181855cd6

    Article  PubMed  Google Scholar 

  • Large MM, Nielssen O (2011) Violence in first-episode psychosis: a systematic review and meta-analysis. Schizophr Res 125:209–220

    Article  PubMed  Google Scholar 

  • Leucht S, Samara M, Heres S, Patel MX, Woods SW, Davis JM (2014) Dose equivalents for second-generation antipsychotics: the minimum effective dose method. Schizophr Bull 40:314–326. doi:10.1093/schbul/sbu001

    Article  PubMed Central  PubMed  Google Scholar 

  • Leucht S, Samara M, Heres S, Patel MX, Furukawa T, Cipriani A, Geddes J, Davis JM (2015) Dose equivalents for second-generation antipsychotic drugs: the classical mean dose method. Schizophr Bull. doi:10.1093/schbul/sbv037

    Google Scholar 

  • Lincoln TM, Hodgins S (2008) Is lack of insight associated with physically aggressive behavior among people with schizophrenia living in the community? J Nerv Ment Dis 196:62–66. doi:10.1097/NMD.0b013e31815faa4d

    Article  PubMed  Google Scholar 

  • Marder SR, Davis JM, Chouinard G (1997) The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials. J Clin Psychiatry 58:538–546

    Article  CAS  PubMed  Google Scholar 

  • Mickey RM, Greenland S (1989) The impact of confounder selection criteria on effect estimation. Am J Epidemiol 129:125–137

    CAS  PubMed  Google Scholar 

  • Soyka M, Graz C, Bottlender R, Dirschedl P, Schoech H (2007) Clinical correlates of later violence and criminal offences in schizophrenia. Schizophr Res 94:89–98. doi:10.1016/j.schres.2007.03.027

    Article  PubMed  Google Scholar 

  • Steinert T, Wölfle M, Gebhardt RP (2000) Measurement of violence during in-patient treatment and association with psychopathology. Acta Psychiatr Scand 102:107–112

    Article  CAS  PubMed  Google Scholar 

  • Swanson JW, Swartz MS, Elbogen EB (2004a) Effectiveness of atypical antipsychotic medications in reducing violent behavior among persons with schizophrenia in community-based treatment. Schizophr Bull 30:3–20

    Article  PubMed  Google Scholar 

  • Swanson JW, Swartz MS, Elbogen EB, Van Dorn RA (2004b) Reducing violence risk in persons with schizophrenia: olanzapine versus risperidone. J Clin Psychiatry 65:1666–1673

    Article  CAS  PubMed  Google Scholar 

  • Taylor PJ, Hill J, Bhagwagar Z, Darjee R, Thomson LDG (2008) Presentations of psychosis with violence: variations in different jurisdictions. A comparison of patients with psychosis in the high security hospitals of Scotland and England. Behav Sci Law 26:585–602. doi:10.1002/bsl.838

    Article  PubMed  Google Scholar 

  • Volavka J, Citrome L (2008) Heterogeneity of violence in schizophrenia and implications for long-term treatment. Int J Clin Pract 62:1237–1245. doi:10.1111/j.1742-1241.2008.01797.x

    Article  CAS  PubMed  Google Scholar 

  • Volavka J, Czobor P, Nolan K, Sheitman B, Lindenmayer J-P, Citrome L, McEvoy JP, Cooper TB, Lieberman JA (2004) Overt aggression and psychotic symptoms in patients with schizophrenia treated with clozapine, olanzapine, risperidone, or haloperidol. J Clin Psychopharmacol 24:225–228

    Article  CAS  PubMed  Google Scholar 

  • Volavka J, Czobor P, Derks EM, Bitter I, Libiger J, Kahn RS, Fleischhacker WW, EUFEST Study Group (2011) Efficacy of antipsychotic drugs against hostility in the European first-episode schizophrenia trial (EUFEST). J Clin Psychiatry 72:955–961. doi:10.4088/JCP.10m06529

    Article  PubMed  Google Scholar 

  • Volavka J, Czobor P, Citrome L, Van Dorn RA (2014) Effectiveness of antipsychotic drugs against hostility in patients with schizophrenia in the clinical antipsychotic trials of intervention effectiveness (CATIE) study. CNS Spectr 19:374–381. doi:10.1017/S1092852913000849

    Article  PubMed Central  PubMed  Google Scholar 

  • Voyer M, Jaafari N, Senon J-L (2011) Insight et comportements violents chez les patients souffrant d’une schizophrénie. Ann Méd-Psychol Rev Psychiatr 169:441–443. doi:10.1016/j.amp.2011.06.006

    Google Scholar 

  • Wang X, Savage R, Borisov A, Rosenberg J, Woolwine B, Tucker M, May R, Feldman J, Nemeroff CB, Miller AH (2006) Efficacy of risperidone versus olanzapine in patients with schizophrenia previously on chronic conventional antipsychotic therapy: a switch study. J Psychiatr Res 40:669–676. doi:10.1016/j.jpsychires.2006.03.008

    Article  PubMed  Google Scholar 

Download references

Acknowledgments and funding source

This work was funded by AP-HP (Assistance Publique des Hôpitaux de Paris), Fondation Fondamental (RTRS Santé Mentale), by the Investissements d’Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01, and by INSERM (Institut National de la Santé et de la Recherche Médicale). We express all our thanks to the nurses and to the patients who were included in the present study.

Author information

Authors and Affiliations

  1. Fondation FondaMental, Créteil, France

    G. Fond, L. Boyer, L. Brunel, B. Aouizerate, F. Berna, D. Capdevielle, I. Chereau, J. M. Dorey, C. Dubertret,  Dubreucq, C. Faget, F. Gabayet, H. Laouamri, C. Lancon, Y. Le Strat, D. Misdrahi, R. Rey, C. Passerieux, A. Schandrin, F. Schurhoff, A. M. Tronche, M. Urbach, P. M. Llorca & A. Pelissolo

  2. INSERM U955, équipe de psychiatrie translationnelle, Créteil, France, Université Paris-Est Créteil, DHU Pe-PSY, Pôle de Psychiatrie des Hôpitaux Universitaires H Mondor, 40 rue de Mesly, F-94010, Créteil, France

    G. Fond, M. Favez, L. Brunel, F. Schurhoff & A. Pelissolo

  3. Pôle Psychiatrie Universitaire, CHU Sainte-Marguerite, F-13274, Marseille cedex 09, France

    L. Boyer

  4. Centre Hospitalier Charles Perrens, Université de Bordeaux, F-33076, Bordeaux, France

    B. Aouizerate & D. Misdrahi

  5. INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France

    F. Berna & P. Vidalhet

  6. Service Universitaire de Psychiatrie Adulte, Hôpital la Colombière, CHRU Montpellier, Université Montpellier 1, Inserm 1061, Montpellier, France

    D. Capdevielle & A. Schandrin

  7. CMP B, CHU, EA 7280 Faculté de Médecine, Université d’Auvergne, BP 69 63003, Clermont-Ferrand Cedex 1, France

    I. Chereau, A. M. Tronche & P. M. Llorca

  8. Université Claude Bernard Lyon 1/Centre Hospitalier Le Vinatier, Pole Est BP 300 39-95 bd, Pinel - 69678, BRON Cedex, France

    J. M. Dorey & R. Rey

  9. AP-HP, Department of Psychiatry, Louis Mourier Hospital, Colombes, Inserm U894, Université Paris Diderot, Faculté de médecine, Sorbonne, Paris Cité, France

    C. Dubertret & Y. Le Strat

  10. Centre Référent de Réhabilitation Psychosociale, CH Alpes Isère, Grenoble, France

    Dubreucq & F. Gabayet

  11. Assistance Publique des Hôpitaux de Marseille (AP-HM), Pôle Universitaire de Psychiatrie, Marseille, France

    C. Faget & C. Lancon

  12. Service de psychiatrie d’adulte, Centre Hospitalier de Versailles, UFR des Sciences de la Santé Simone Veil, Université Versailles Saint-Quentin en Yvelines, Versailles, France

    C. Passerieux & M. Urbach

  13. Bordeaux Sleep Clinique, Pellegrin University Hospital, USR CNRS 3413 SANPSY, Research Unit, Bordeaux University, 33000, Bordeaux, France

    G. Fond, L. Boyer, M. Favez, L. Brunel, B. Aouizerate, F. Berna, D. Capdevielle, I. Chereau, J. M. Dorey, C. Dubertret,  Dubreucq, C. Faget, F. Gabayet, H. Laouamri, C. Lancon, Y. Le Strat, D. Misdrahi, R. Rey, C. Passerieux, A. Schandrin, F. Schurhoff, A. M. Tronche, M. Urbach, P. Vidalhet, P. M. Llorca & A. Pelissolo

  14. Inserm, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000, Bordeaux, France

    B. Aouizerate

  15. CNRS UMR 5287-INCIA, Bordeaux, France

    D. Misdrahi

Authors
  1. G. Fond
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  2. L. Boyer
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  3. M. Favez
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  4. L. Brunel
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  5. B. Aouizerate
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  6. F. Berna
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  7. D. Capdevielle
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  8. I. Chereau
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  14. H. Laouamri
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  15. C. Lancon
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  16. Y. Le Strat
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  18. R. Rey
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  19. C. Passerieux
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  22. A. M. Tronche
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  23. M. Urbach
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  25. P. M. Llorca
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  26. A. Pelissolo
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Consortia

And the FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) group*

Corresponding author

Correspondence to G. Fond.

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Conflict of interest

The authors declare that they have no competing interests.

Additional information

*FACE-SCZ Group

Aouizerate Ba,l, MD PhD, Berna Fb,l, MD PhD, Blanc Oc,l, Msc, Brunel Ld,l, Msc, Bulzacka Ed,l, Msc, Capdevielle De,l, MD PhD, Chereau-Boudet Ic,l, MD, Chesnoy-Servanin Gf,l, Msc, Danion JMb,l, MD, D’Amato Tf,l, MD PhD, Deloge Ag,l, MD PhD, Delorme Ch,l, Msc, Denizot Hc,l, MD, De Pradier Mi,l, MD, Dorey JMf,l, MD, Dubertret Ci,l, MD PhD, Dubreucq Jh,l, MD, Faget Cj,l, MD, Fluttaz Ch,l, Msc, Fond Gd,l, MD, Fonteneau Sk,l, Msc, Gabayet Fh,l, Msc, Giraud-Baro Eh,l, MD, Hardy-Bayle MCk,l, MD PhD, Lacelle Dc,l, Msc, Lançon Cj,l, MD PhD, Laouamri Hl, Msc, Leboyer Md,l, MD PhD, Le Gloahec Td,l, Msc, Le Strat Yi,l, MD PhD, Llorcac,l PM, MD PhD, Metairie Ej,l, Msc, Misdrahi Dg,l, MD, Offerlin-Meyer Ib,l, PhD, Passerieux Ck,l, MD PhD, Peri Pj,l, Msc, Pires Sc,l, Msc, Portalier Ci,l, Msc, Rey Rf,l, MD, Roman Ch,l, Msc, Sebilleau Mk,l, Msc, Schandrin Ae,l, MD, Schurhoff Fd,l, MD PhD, Tessier Ag,l, Msc, Tronche AMc,l, MD, Urbach Mk,l, MD, Vaillant Fj,l, Msc, Vehier Af,l, Msc, Vidailhet Pb,l, MD PhD, Vilain Jd,l, MD, Vilà Eg,l, Msc, Yazbek He,l, PhD, Zinetti-Bertschy A, Msc.

aCentre Hospitalier Charles Perrens, F-33076 Bordeaux, France; Université de Bordeaux, Inserm, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France

bHôpitaux Universitaires de Strasbourg, Université de Strasbourg, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France

cCMP B, CHU, EA 7280 Faculté de Médecine, Université d’Auvergne, BP 69 63003 Clermont-Ferrand Cedex 1,

dINSERM U955, équipe de psychiatrie translationnelle, Créteil, France, Université Paris-Est Créteil, DHU Pe-PSY, Pôle de Psychiatrie des Hôpitaux Universitaires H Mondor, Créteil, France

eService Universitaire de Psychiatrie Adulte, Hôpital la Colombière, CHRU Montpellier, Université Montpellier 1, Inserm 1061, Montpellier, France.

fUniversité Claude Bernard Lyon 1/Centre Hospitalier Le Vinatier Pole Est BP 300 39-95 bd Pinel - 69678 BRON Cedex, France.

gCentre Hospitalier Charles Perrens, F-33076 Bordeaux, France; Université de Bordeaux, CNRS UMR 5287-INCIA

hCentre Référent de Réhabilitation Psychosociale, CH Alpes Isère, Grenoble, France.

iAP-HP, Department of Psychiatry, Louis Mourier Hospital, Colombes, Inserm U894 Université Paris Diderot, Sorbonne Paris Cité, Faculté de médecine, France.

jAssistance Publique des Hôpitaux de Marseille (AP-HM), pôle universitaire de psychiatrie, Marseille, France.

kService de psychiatrie d’adulte, Centre Hospitalier de Versailles, Le Chesnay, EA 4047 HANDIReSP, UFR des Sciences de la Santé Simone Veil, Université Versailles Saint-Quentin en Yvelines, Versailles, France.

lFondation Fondamental

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Fond, G., Boyer, L., Favez, M. et al. Medication and aggressiveness in real-world schizophrenia. Results from the FACE-SZ dataset. Psychopharmacology 233, 571–578 (2016). https://doi.org/10.1007/s00213-015-4167-8

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