What Is the Best Pharmacotherapy for Violent or Aggressive Behavior?

Mary E. Muscari, PhD, CPNP, APRN-BC,CFNS


October 04, 2006


On an inpatient short-term psychiatric unit, what medications are most useful to abate violent or aggressive behaviors?

Response From the Expert

Mary E. Muscari, PhD, CPNP, APRN-BC,CFNS 
Professor, Director of Forensic Health/Nursing, University of Scranton, Scranton, Pennsylvania; Pediatric Nurse Practitioner, Psychological Clinical Specialist, Forensic Clinical Specialist, Lake Ariel, Pennsylvania


Violence usually denotes physical acts against other persons, whereas aggression encompasses physical acts against others, oneself, or objects, as well as verbal assaults. Although most patients with psychiatric disorders are not aggressive, epidemiologic evidence shows an increased risk for violence in this group when compared with the general population. Violent or threatening behavior is a frequent cause for admission to a psychiatric unit, and this behavior may persist after admission.[1]

Aggression in patients with psychiatric disorders has several possible causes. Differentiating among these causes is essential in order to determine the appropriate therapy[1,2,3]:

  • The most important causes may be comorbid substance abuse, dependence, and intoxication. Alcohol, cocaine, phencyclidine (PCP), and amphetamine use can lead to aggression as well as caffeine, water, or antihistamine intoxication and the ingestion of deodorants and aerosols. Substance withdrawal can lead to aggression due to drug-seeking behavior, paranoia, or extreme anxiety.

  • Aggression is a common manifestation of many neuropsychiatric disorders, including traumatic brain injury, cerebral vascular accidents, Huntington's disease, and dementia. Medical and neurologic conditions may precipitate aggression in patients who are not normally violent, and dementia can result in emotional lability and poor impulse control.

  • The disease process in psychotic disorders, including schizophrenia and mania, can produce hallucinations or delusions that may provoke aggression. This aggression is usually related to noncompliance with or failure of current medication regimes.

  • Impulsivity and aggressive behavior may be a component of cluster B personality disorders (antisocial, borderline, narcissistic, and histrionic), developmental disorders, impulse-control disorders, attention-deficit/hyperactivity disorder, Tourette's syndrome, and posttraumatic stress disorder.

  • Finally, environmental factors may be associated with aggression. Chaotic, unstable home or hospital situations may encourage maladaptive aggressiveness.

  • Aggression may be subtyped into nonmutually exclusive dimensions: acute vs chronic, verbal vs physical, overt vs covert, adaptive vs maladaptive, and reactive-affective-defensive-impulsive vs proactive-instrumental-planned-predatory. Each of these subtypes has treatment implications.

The acute subtype is often encountered in acute psychiatric wards, as well as hospital emergency departments. When acute aggression presents, the clinician may not have adequate time to conduct a thorough evaluation and, thus, may need to use a targeted treatment approach with medications that have a rapid calming effect, such as sedating antihistamines or antipsychotic medications.[4]

Pharmacologic Treatment of Aggression

Medications are frequently used in the management of aggression, and current psychopharmacologic treatment strategies involve treating aggression as part of each particular syndrome. Acute management focuses on calming the agitated patient, whereas chronic management aims to reduce the frequency and intensity of episodes of agitation. Long-term treatment is directed toward the underlying disorder. Additional adjunctive medications may be necessary when standard therapeutic approaches are ineffective.[5]

Agitated patients should be offered medications as early as possible. Medication choice depends on several factors, most notably the patient's history and the assessment, even though there may be little time for a thorough assessment when an aggressive patient is a danger to him/herself or others. Medical conditions (infectious, toxic, physiologic, and metabolic causes of aggression) should be identified because they may require treatment and may affect psychopharmacologic treatment.[1,5]


Lorazepam (Ativan) is a good choice to treat acute agitation or aggression, particularly when the etiology is not clear. It is safe and effective, and is the only benzodiazepine that is reliably absorbed when administered intramuscularly. Lorazepam may also be administered orally, sublingually, or intravenously. The drug should be used with caution when respiratory distress is possible, and the clinician should be aware that benzodiazepines can cause paradoxical reactions. Benzodiazepines also have a risk for abuse, and therefore should not be used on a regular basis.


First-generation antipsychotics. Neuroleptics cause sedation when administered in high doses. Haloperidol (Haldol) can be used intramuscularly as needed for agitation and aggression in a wide variety of patients. Haloperidol causes less hypotention and fewer anticholinergic side effects than low-potency neuroleptics, such as chlorpromazine (Thorazine). However, the low-potency neuroleptics are sometimes preferred because clinicians desire a more sedating agent.

By also treating any underlying psychosis, neuroleptics can have a longer-lasting effect on agitation. Acute mania can be quickly and effectively controlled with neuroleptics, and these medications have been used to manage aggression in the elderly. However, high doses of neuroleptics can result in more adverse side effects, including akathisia (inability to sit still).

Second-generation or atypical antipsychotics. Second-generation antipsychotic medications are becoming important options in the management of acute aggression in persons with psychosis. They have a lower risk for extrapyramidal effects, such as akathisia and tardive dyskinesia (repetitive, purposeless, involuntary movements), and they may have a specific antiaggressive effect over time. Commonly used atypicals include ziprasidone (Geodon), clozapine (Clozaril), risperidone (Risperdal), and olanzapine (Zyprexa).

Antipsychotic medications are not recommended for patients who do not have a psychotic or bipolar disorder. Lorazepam or another nonspecific sedating agent is preferred. However, one study demonstrated that clozapine reduced aggression and self-injurious behavior in persons with metal retardation.[2]


Antidepressants reduce fear, irritability, and anxiety, emotions that are in the same spectrum as agitation. Current findings point to decreases in negative mood and aggressive attacks, as well as positive changes in personality traits after antidepressant treatment. Personality disorder patients have also shown reduced irritability and impulsive aggression when treated with serotonergic antidepressants,[6] and patients with posttraumatic agitation have responded to amitriptyline (Elavil).

Fluoxetine (Prozac) has been shown to reduce impulsiveness in patients with borderline personality disorder, but has also been blamed for inducing homicide or suicide. Therefore, it is recommended that this medication be used with caution.

Mood Stabilizers

Mood stabilizers are primarily used for the treatment of bipolar disorder and as an adjunct treatment for schizophrenia. They are also used to treat aggression, although they are not prototypical for this purpose. Valproate (Depakene) has been used to control aggression in a number of psychiatric conditions, such as dementia, borderline personality disorder, organic mood syndrome, bipolar disorder, schizophrenia, schizoaffective disorder, and mental retardation. Divalproex (Depakote) and carbamazepine (Tegretol) are widely used to treat impulsivity and aggression, and carbamazepine is also used to treat the aggressive symptoms of dementia. Unfortunately, the side effects of carbamazepine, ranging from dizziness, ataxia, and drowsiness to agranulocytosis and hepatotoxicity, limit is use. Divalproex produces less side effects and is less likely to cause drug interactions; thus, it is usually a more favored mood stabilizer for patients with dementia.

Aggression reduction during manic episodes is an important function of lithium carbonate (Eskalith). Lithium is also used for the aggressive features of mental retardation, and it has been used to reduce the number of infractions involving violent behavior of recurrently violent prisoners. Although effective, tolerability problems can limit its use.

Beta Blockers

Beta-adrenergic blockers, especially propranolol (Inderal), have been used to treat aggressive behavior in a number of diagnoses, including mental retardation, autism, posttraumatic brain syndromes, dementia, Huntington's disease, Wilson's disease, postencephalitic psychosis, and apparent or presumed chronic central nervous system dysfunction inferred from soft neurologic signs, abnormal electroencephalographic (EEG) findings, or clinical seizures.

Propranolol is also used as an adjunctive treatment to reduce aggressive symptoms in patients with schizophrenia. The main problem with the use of propranolol for aggression is the high frequency of adverse cardiovascular effects. Other beta blockers used in the treatment of aggression are pindolol (Visken), metoprolol (Lopressor) — which has also shown to be effective in the treatment of intermittent explosive disorder, — and nadolol (Corgard).

Choosing the Best Pharmacologic Approach

Before prescribing medication therapy for aggression, the clinician should ensure that the patient has a medical evaluation to rule out contraindications to treatment and to determine whether the patient's aggressive symptoms might improve with appropriate medical care. Psychiatric evaluation is also necessary to determine whether psychosis, depression, anxiety, substance abuse, or other problems are present. Treatment of these conditions may also result in reduced symptoms of aggression. Nonpharmacologic measures should be instituted; however, when pharmacologic treatment is warranted, institute treatment with an antiaggression medication that best fits the patient's symptom cluster.


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