Psychopharmacology of Aggression in Schizophrenia

Peter Buckley; Leslie Citrome; Carmen Nichita; Michael Vitacco


Schizophr Bull. 2011;37(5):930-936. 

In This Article

Abstract and Introduction


The management of aggression in patients with schizophrenia is a complex and challenging clinical dilemma. It also is greatly influenced by prevailing societal and medicolegal considerations regarding the perceived associations between violence and mental illness. This article provides a succinct account of a complex area and offers evidence for available treatments to reduce the occurrence of violent behavior among patients with schizophrenia.


The treatment of patients with schizophrenia who are aggressive is particularly challenging. Our capacity for accurate prediction of violent behavior—itself a daunting task—juxtaposes our responsibilities for societal risk alongside our responsibility to provide and safe care to the psychotic patient who is/could become violent. Moreover, the choice of the treatment methods varies depending on the possible cause of aggression: is the aggression stemming directly from psychosis or due to some other comorbidity, eg, traumatic brain injury or mental retardation or due to the personality disorder? For a long time, the clinicians had available only the typical (first generation) antipsychotics to reduce aggression, and often "megadoses" were used and/or potentially coercive use when noncompliance involved long-acting injectable.[1]

Complicating medication choice is the multifactorial etiology for the agitated behavior. This requires the assessment of the patient for possible comorbidities, such as somatic conditions or other psychiatric conditions, or adverse effects of medications, such as akathisia. In particular, special consideration needs to be made for patients who may be in acute alcohol or sedative withdrawal where reduction of the seizure threshold with the use of antipsychotics can be problematic. In these instances, medications that are cross-tolerant with alcohol, such as lorazepam (well absorbed intramuscularly), are preferred because they will treat the potential withdrawal state as well as exert a calming effect. However, these agents do not address the underlying core psychotic illness, and long-term use of a benzodiazepine can also result in physiological tolerance, leading to potential rebound anxiety or agitation in between doses or when doses are missed. Moreover, the underlying causes for the propensity toward aggression are themselves complex.[1,2] Herein, we briefly illuminate core principles—both legal and clinical—and practices that currently guide our management of this complicated clinical scenario.