Psychopharmacological Treatment of Aggression in Schizophrenic Patients

T. Brieden; M. Ujeyl; D. Naber

doi:10.1055/s-2002-31523

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2002; 35(3): 83-89
DOI: 10.1055/s-2002-31523

Review

Psychopharmacological Treatment of Aggression
in Schizophrenic Patients

T. Brieden, M. Ujeyl, D. Naber

¹Department of Psychiatry and Psychotherapy, Hamburg-Eppendorf University Hospital, Germany

Abstract

Aggressive behavior is frequently observed in schizophrenic patients. More than 50 % of all psychiatric patients and 10 % of schizophrenic patients show aggressive symptoms varying from threatening behavior and agitation to assault. The pharmacological treatment of acute, persisting and repetitive aggression is a serious problem for other patients and staff members. Not only is violent behavior from mentally ill patients the most detrimental factor in their stigmatization, aggression is also a considerable direct source of danger for the patients themselves.

Based on rather limited evidence, a wide variety of medications for the pharmacological treatment of aggression has been recommended: typical and atypical antipsychotics, benzodiazepines, mood stabilizers, beta-blockers and selective serotonin reuptake inhibitors (SSRIs).

Most clinical information on treating aggression has been collected for atypical neuroleptics, particularly for clozapine. Several retrospective and open studies indicate its efficacy. Treatment duration of 6 months is recommended to induce a stable reduction of physical and verbal aggression. Severe side effects have very rarely been seen. At the moment, clozapine seems to be the first choice in aggression treatment. Within the last few years, about 10 articles were published showing that this is the most effective antiaggressive agent in the treatment of aggression and agitation in psychiatric patients, independent of psychiatric diagnosis. However, clozapine, like all the other substances used, does not have an established indication for the treatment of aggressive symptoms. Noncompliance with medication makes it difficult to choose the right preparation for the medication: tablets, liquids, intramuscular injections and readily soluble “FDDFs” are available. Ethical, juridical and methodological problems prevent controlled studies from establishing a reference in the treatment of aggression in mentally ill patients. This review summarizes the current discussion and publications on the pharmacological treatment of aggression in schizophrenic patients of the last 20 years. In addition, we will briefly present studies and case reports concerning the treatment of aggression in other psychiatric patients.

Full Text

References

1 Bienik S A, Ownby R L, Penalver A, Dominguez R A. A double-blind study of lorazepam versus the combination of haloperidol and lorazepam in managing agitation. Pharmacotherapy. 1998; 18 57-62
2 Brecher M, Clyde C, Group T RS. Risperidone in the treatment of psychosis and aggressive behavior in patients. In: Las Croabas Puerto Rico; The American College of Neuropsychopharmacology 1998
3 Buckley P F. The role of typical and atypical antipsychotic medications in the management of agitation and aggression. J Clin Psych. 1999; 60 (10) 52-60
4 Buckley P F, Bartell J, Donenwirth K, Lee S, Torigoe F, Schulz S C. Violence and schizophrenia: clozapine as a specific antiaggressive agent. Bull Am Acad Psych Law. 1995; 23 607-611
5 Buckley P F, Ibrahim Z Y, Singer B, Orr B, Donenwirth K, Brar P S. Aggression and schizophrenia: efficacy of risperidone. J Am Acad Psych Law. 1997; 25 173-181
6 Cabrera J F, Körner W, Müller-Oerlinghausen B. Erfolgreiche kombinierte Neuroleptika-Lithium-Behandlung eines chronisch schizophrenen Kranken mit rezidivierendem aggressivem Verhalten. Nervenarzt. 1986; 57 366-369
7 Campbell M, Cohen I L, Small A M. Drugs in aggressive behavior. J Am Acad Child Psychiatry. 1982; 21 107-117
8 Campbell M, Small A M, Green W H, Jennings S J, Perry R, Bennet W G, Andersson L. Behavioral efficacy of haloperidol and lithium carbonate. A comparison in hospitalized aggressive children with conduct disorders. Arch Gen Psychiat. 1984a; 41 650-656
9 Campbell M, Perry R, Green W H. Use of lithium in children and adolescents. Psychosomatics. 1984b; 25 95-106
10 Campbell M, Adams P B, Small A M, Kafantaris V, Silva R R, Shell J, Overall J E. Lithium in hospitalized aggressive children with conduct disorder: a double-blind and placebo-controlled study. J Am Acad Child Adolesc Psychiatry. 1995; 34 445-453
11 Chiles J A, Davidson P, McBride D. Effects of clozapine on use of seclusion and restraint in a state hospital. Hosp Comm Psych. 1994; 45 269-271
12 Corrigan P W, Yudolfsky S C, Silver J M. Pharmacological and behavioral treatments for aggressive psychiatric inpatients. Hosp Comm Psych. 1993; 44 125-133
13 Curtis J L. Psychotropic medication use in people with developmental disabilities. Md Med J. 1997; 46 481-485
14 Czobor P, Volavka J, Meibach R C. Effect of risperidone on hostility in schizophrenia. J Clin Psychopharmacol. 1995; 15 243-249
15 Dorevitch A, Katz N, Zemishlany Z, Aizenberg D, Weizman A. Intramuscular Flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior. Am J Psychiatry. 1999; 156 142-144
16 Dubin W R. Rapid tranquillisation: antipsychotics or benzodiazepines?. J Clin Psych. 1988; 49 (12) 5-12
17 Ebrahim G M, Gibler B, Gacono G B. Patient response to clozapine in a forensic psychiatric hospital. Hosp Comm Psych. 1994; 45 271-273
18 Eimer M. Management of the behavioral symptoms associated with dementia. Prim Care. 1989; 16 431-450
19 Elphick M. Clinical issues ina the use of carbamazepine in psychiatry: a review. Psychol Med. 1989; 19 591-604
20 Fava M. Psychopharmacologic treatment of pathologic aggression. Psych Clin North Am. 1997; 20 427-451
21 Fritze J, Beneke M, Lanczik M, Schneider B, Walden J. Carbamazepine as adjunct or alternative to lithium in the prophylaxis of recurrent affective disorders. Pharmacopsychiat. 1994; 27 181-185
22 Garmendia L, Sanchez J R, Azpiroz A, Brain P F, Simon V M. Clozapine: strong antiaggressive effects with minimal motor impairment. Physiol Behav. 1991; 51 51-54
23 Glazer W M, Dickson R A. Clozapine reduces violence and persistent aggression in schizophrenia. J Clin Psych. 1998; 59 (3) 8-14
24 Goldberg R J, Dubin W R, Fogel B S. Review: Behavioral emergencies, assessment of psychopharmacologic management. Clin Neuropharm. 1989; 12 233-248
25 Greendyke R M, Kanter D R, Schuster D B, Verstreate S, Wootton J. Propanolol treatment of assaultive patients with organic brain disease. A double-blind crossover, placebo-controlled study. J Nerv Ment Dis. 1986; 174 290-294
26 Grossman F. A review of anticonvulsants in treating agitated demented elderly patients. Pharmacotherapy. 1998; 18 600-606
27 Hector R I. The use of clozapine in the treatment of aggressive schizophrenia. Can J Psych. 1998; 43 466-472
28 Laurijssens B E, Greenblatt D J. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokin. 1996; 30 52-76
29 Laux G, Dietmeier O, König W. Psychopharmaka - ein Leitfaden. 5. Aufl. Ulm, Stuttgart, Jena, New York; Fischer 1995
30 Lemke M R, Stuhlmann W. Therapeutische Anwendung von Carbamazepin bei Antriebssteigerung und Affektstörungen gerontopsychiatrischer Patienten. Psychiatrische Praxis. 1994; 21 147-150
31 Lenox R H, Newhouse P A, Creelman W L, Whitacker T M. Adjunctive treatment of manic agitation with lorazepam versus haloperidol: a double-blind study. J Clin Psych. 1992; 53 47-52
32 Luchins D J. Carbamazepine in violent non-epileptic schizophrenics. Psychopharmacology Bulletin. 1984; 20 (3) 569-571
33 Mallya A R, Roos P D, Roebuck-Colgan K. Restraint, seclusion, and clozapine. J Clin Psych. 1992; 53 395-397
34 Marder S R, Davis J M, Chouinard G. The effects of rsiperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trial. Jour Clin Psych. 1997; 58 (12) 538-546
35 Markovitz P J, Calabrese J R, Schulz S C, Meltzer H Y. Fluoxetine in the treatment of borderline and schizotypal personality disorder. Am J Psych. 1991; 148 1064-1067
36 Mattes J A. Carbamazepine vs. propanolol for rage outbursts. Psychopharmacol Bull. 1988; 24 179-182
37 McDougle C J, Homes J P, Carlson D C. A double-blind placebo controlled study of rsiperidone in adults with autistic disorder and other pervasive developmental disorders. Arch Gen Psych. 1998; 55 633-641
38 McDouble C J, Naylor S T, Cohen D J, Volkmar F R, Heninger G R, Price L H. A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder. Arch Gen Psychiatry. 1996; 53 1001-1008
39 Morrison E F. A hierachy of aggressive and violent behaviors among psychiatric inpatients. Hosp Comm Psych. 1992; 43 505-506
40 Nilsson A. Lithium in der Therapie und Prophylaxe pathologischer Aggression. In: Müller-Oerlinghausen B (ed) Die Lithiumtherapie: Nutzen, Risiken, Alternativen. Berlin; Springer 1997: 278-289
41 Nissen G, Fritze J, Trott G E. Psychopharmaka im Kindes- und Jugendalter. Ulm, Stuttgart, Jena, Lübeck; Fischer 1998
42 Okuma T, Yamashita I, Takahashi R. A double-blind study of adjunctive carbamazepine versus placebo on excited states of schizophrenia and schizoaffective disorders. Acta Psychiatr Scand. 1989; 80 250-259
43 Pabis D J, Stanislaw S W. Pharmacotherapy of aggressive behavior. Ann Pharmacother. 1996; 30 278-287
44 Pilowsky L S, Ring H, Shine P J, Battersby M, Lader M. Rapid tranquillisation - a survey of emergency prescribing in a general psychiatric hospital. Br J Psych. 1992; 160 831-835
45 Polakoff S A, Sorgi P J, Ratey J J. The treatment of impulsive and aggressive behavior with nadolol. J Clin Psychopharmacol. 1996; 6 125-126
46 Rabinowitz J, Avnon M, Rosenberg V. Effect of clozapine on physical and verbal aggression. Schizophr Res. 1996; 22 249-255
47 Ratey J J, Leveroni C, Kilmer D. The effects of clozapine on severely aggressive psychiatric inpatients in a state hospital. J Clin Psych. 1993; 54 219-223
48 Rittmannsberger H. Carbamazepin in der Behandlung psychischer Erkrankungen: Wirkungen und Nebenwirkungen. Wiener Med Woch. 1990; 15 398-404
49 Ruedrich S L, Grush L, Wilson J. Beta adrenergic blocking medications for aggressive and self-injurious mentally retarded persons. Am J Mental Retard. 1990; 95 110-119
50 Salzman C, Solomon D, Miyawaki E, et al. Parenteral lorazepam versus parenteral haloperidol for the control of psychiatric disorder behavior. J Clin Psych. 1991; 52 177-180
51 Schneider L S, Sobin P B. Non-neuroleptic treatment of behavioral symptoms and agitation in Alzheimer's disease and other dementia. Psychopharm Bull. 1992; 28 71-79
52 Sheppard G P. High-dose propanolol in schizophrenia. Br J Psych. 1979; 134 470-476
53 Silver H, Kushnir M. Treatment of aggression in schizophrenia. Br J Psych. 1998; 155 1298
54 Sorgi P J, Ratey J J, Polakoff S. Beta-adrenergic blockers for the control of aggressive behavior in patients with chronic schizophrenia. Am J Psych. 1986; 143 775-776
55 Stanislaw S. Neuere Tendenzen in der Pharmakotherapie aggressiven Verhaltens bei psychisch Kranken. Fortschr Neurol Psychiatr. 1992; 60 393-400
56 Steinert T. Neuere Tendenzen in der Pharmakotherapie aggressiven Verhaltens bei psychisch Kranken. Fortschr Neurol Psychiatr. 1992; 60 393-400
57 Steinert T, Sippach T, Gebhardt R P. How common is violence in schizophrenia despite neuroleptic treatment?. Pharmacopsych. 2000; 33 98-102
58 Swanson J, Holzer C, Ganju V. volence and psychiatric disorder in the community: evidence from the Epidemiologic Catchment area surveys. Hosp Comm Psych. 1990; 41 761-770
59 Tauscher J, Kasper S. Sertralin - selektiver Serotonin-Wiederaufnahmehemmer mit geringem Interaktionsprofil. Fundamenta Psychiatrica. 1997; 11 179-189
60 Taylor P J. Schizophrenia and crime: distinctive patterns in association. In: Hodgins S (ed) Crime and mental disorder. Newbury Park, CA USA; Sage Publications 1993
61 Tyrer S P, Walsh A, Edwards D E, Berney T P, Stephens D A. Factors associated with a good response to lithium in aggressive mentally handicapped subjects. Prog Neuropsychopharmacol. 1984; 8 751-755
62 Vartiainen H, Tiihonen J, Putkonen A, Koponen H, Virkkkunen M, Hakola P. Citalopram, a selective serotinin reuptake inhibitor, in the treatment of aggression in schizophrenia. Acta Psychiatr Scan. 1995; 91 348-351
63 Volavka J. The effects of clozapine on aggression and substance abuse in schizophrenic patients. J Clin Psych. 1999; 60 (12) 43-46
64 Volavka J. The neurobiology of violence. Washington DC, USA; Am Psych Press 1995
65 Volavka J, Citrome L. Atypical antipsychotics in the treatment of persistently aggressive psychotic patients: methodological concerns. Schizophrenia Res. 199; 35 S23-S33
66 Volavka J, Zito J M, Vitrai J, Czobor P. Clozapine effects on hostility and aggression in schizophrenia. J Clin Psychopharmacol. 1993; 13 287-289
67 Weiden P J, Olfson M. Cost of relapse in schizophrenia. Schizophr Bull. 1995; 21 419-429
68 Wessely S. the epidemiology of crime, violence and schizophrenia. Br J Psych. 1997; 170 (32) 8-11
69 Wilson W H. Clinical review of clozapine treatment in a state hospital. Hosp comm Psych. 1992; 43 700-703
70 Wroblewski B A, Joseph A B, Kupfer J, Kalliel K. Effectiveness of valproic acid on destructive and aggressive behaviors in patients with acquired head injury. Brain Inj. 1997; 11 37-47
71 Yudofsky S C, Silver J M, Jackson W, Endicott J, Williams D. The overt aggression scale for the objective rating of verbal and physical aggression. Am J Psychiatry. 1986; 143 35-39
72 Yudofsky S C, Silver J M, Hales R E. Pharmacologic management of aggression in the elderly. J Clin Psych. 1990; 51 (10) 22-28

Prof. Dr. med. Dieter Naber

Department of Psychiatry and Psychotherapy, University Hospital Eppendorf

Martinistraße 52

20246 Hamburg

Germany

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