American Psychiatric Association 153rd Annual Meeting
Day 2 - May 15, 2000

The Treatment and Prevention of Violence

Kathleen Brady, MD, PhD

Violence is a public health problem of major significance. In the United States, homicide was the 13th leading cause of death in 1997.[1] Certain psychiatric diagnoses, including mood disorders, substance use disorders, and psychosis, have been shown to be associated with an increased risk of violent behavior. At the 153rd annual meeting of the American Psychiatric Association in Chicago, Illinois, experts focused on the relationship between violence and psychiatric disorders, with an eye toward preventing and treating violent behavior.

Personality Disorders and Impulsive Aggression

Because impulsive aggression plays a large role in the incidence of violence, understanding the strong association between such behavior and personality disorders is important. The determinants of impulsive aggression include genetic transmission, environmental influences, and biologic abnormalities. Studies of familial transmission of impulsive aggression in individuals with personality disorder indicate that impulsive aggression is more heritable than the personality disorder itself. Studies of families of individuals with intermittent explosive disorder have shown that a number of other psychiatric disorders, including substance abuse and mood disorders, appear to cluster in these families. Environmental factors that contribute to impulsive aggression risk include experiencing or witnessing aggression as a child.[2]

Emil Cocarro, MD,[3,4] has demonstrated that impulsive aggression can be seen in individuals with any type of personality disorder, but is most commonly seen in individuals with paranoid (20%), borderline (23%), obsessive-compulsive (21%), narcissistic (14%) and antisocial (10%) personality disorders.

Cocarro and colleagues[5] have demonstrated an inverse relationship between several measures of serotonin function and impulsive aggression in a group of individuals with personality disorder. Cerebral spinal fluid (CSF) vasopressin levels appear to be positively correlated with impulsive aggression, while there is an inverse correlation between serotonin function and vasopressin. PET scan studies have demonstrated that individuals with intermittent explosive disorder have less serotonin activity in the orbital-frontal cortex than controls.

A number of studies indicate that dysregulation of the serotonin system plays a role in impulsive aggression. For example, CSF 5-HIAA, the major metabolite of serotonin, is decreased in individuals with a history of impulsive aggression compared with those who suffer from nonimpulsive aggression and with normal controls.

Treatment Approaches

A number of agents have been investigated in the treatment of impulsive aggression. Both lithium and phenytoin have been shown in placebo-controlled trials to decrease impulsive aggression in prison inmates.[6] Carbamazepine was shown in one controlled trial to decrease impulsive aggression in individuals with borderline personality disorder.[7] At the same time, amitriptyline has been shown to increase aggression in some individuals with borderline personality disorder.[8]

Recent studies have focused on the use of the serotonin reuptake inhibitors in the treatment of impulsive aggression across the psychiatric disorder spectrum. For example, Cocarro and colleagues[9] have demonstrated a positive effect of fluoxetine in a group of individuals with borderline personality disorder.

Depression and Anger Attacks

Depression and violent behavior are significantly correlated with moderate to severe outwardly directed irritability, as demonstrated by a study in which 37% of depressed patients reported having such irritability. This irritability can translate into an increased numbers of anger attacks, which are sudden spells of anger often associated with autonomic signs of hyperarousal that are inappropriate to the situation. Such attacks have been postulated to be a variant of depressive disorders.

Compared with controls, outpatients with major depressive disorder (MDD) have a significantly higher rate of anger attacks. As many as 38% to 44% of depressed outpatients report anger attacks, which are more common in individuals with unipolar depression than in those with bipolar disorder. MDD patients with anger attacks are also more likely to meet criteria for a comorbid personality disorder. In individuals with MDD, there are marked signs of autonomic arousal associated with anger attacks, including tachycardia, hot flashes, and sweating. More than 90% of individuals with MDD who experience anger attacks report guilt or regret after the anger attack. As many as 60% report attacking an individual physically or verbally and 30% report throwing or destroying objects.[10,11] Maurizio Fava, MD,[12] reported that each 20% increase in depressive symptoms increased the risk of severe aggression against one's spouse by 74%.

A number of studies have suggested that aggression is associated with reduced serotonin function. Dr. Fava reported that he and his colleagues[12] found a blunting of the prolactin response to fenfluramine, a measure of serotonin function, in depressed individuals with anger attacks as compared to depressed individuals without anger attacks. This finding suggests a greater dysregulation of serotonergic neurotransmission in MDD with anger attacks than in MDD alone.

Treatment of Anger Attacks

A number of open-label studies have demonstrated that antidepressant agents, particularly the serotonin reuptake inhibitors, are effective in decreasing anger attacks. The depression response to these agents is equally robust in depressed individuals with and without anger attacks. In individuals with depression without anger attacks, treatment with either fluoxetine or sertraline is associated with less emergence of anger attacks than treatment with placebo.[9] These studies indicate that serotonin reuptake inhibitors can be safely used and show substantial promise in the treatment of anger attacks.

Impact of Newer Antipsychotic Agents on Violence in Psychosis

A history of violence can be elicited from a substantial number of individuals with chronic psychotic illness. This presents a major management problem, particularly as the use of seclusion and restraints in hospital settings is coming under increasing scrutiny. Most of the studies investigating the effectiveness of the newer antipsychotics in decreasing violence in hospitalized patients are limited by the fact that they are not placebo-controlled. Many studies compare the use of seclusion and restraint before and after the introduction of these agents. Despite these methodologic limitations, the results have been remarkably similar across sites and the effect size in existing studies is generally very large.[13]

Treatment Approaches

A number of studies have demonstrated a decrease in the use of seclusion and improvement in measures of aggression and irritability in hospital-based settings since the introduction of clozapine.[14] Similar comparisons for risperidone have demonstrated a decrease in physical assault, seclusion, and restraint. In one study comparing placebo, haloperidol, and risperidone, the risperidone treatment group showed a decrease in hostility measures that was twice as large as the decrease seen in the placebo and haloperidol-treated groups.[15] Olanzapine has been found to decrease aggression in the treatment of acute mania,[16] as well as to decrease agitation in schizophrenic patients.

K.N. Roy Chengappa, MD,[17] Department of Psychiatry, Western Psychiatric Institute reported that another new agent, quetiapine, has demonstrated a decrease in hostility and aggression measures in a group of elderly patients compared with both placebo and haloperidol. These agents are better tolerated and show promise when compared with the older antipsychotic agents in treating hostility and aggression across a number of psychiatric disorders.

Violent Behavior and Substance Abuse: Preventive and Treatment Approaches

The relationships among violence, substance abuse, and aggression are complex. Intoxication by a variety of substances is associated with violent behavior, and some of the neurochemical abnormalities that place individuals at risk for violent behavior are the same as those that increase risk for substance abuse.[18] Studies of emergency room visits resulting from violence indicate that 40% to 80% of such episodes are associated with drug or alcohol abuse.

Nearly half of those arrested for violent crime in the United States demonstrate positive urine drug screens for drugs of abuse, and substance abuse in the home is one of the strongest predictors of domestic violence.[19] This creates a self-perpetuating cycle of substance abuse and violence as children brought up in these homes are more likely to become perpetrators of violence and are at risk for the development of substance use disorders.

Dysregulation of the serotonin system has been implicated as a causal factor in aggression and violent behavior, and there is also considerable evidence that the serotonin system is involved in substance use disorders, particularly alcoholism. As alcohol decreases serotonin synthesis, serotonin depletion is associated with an increase in alcohol-induced aggression in laboratory studies.

Treatment Approaches

Before initiating treatment in individuals with substance use disorders, a careful evaluation of psychiatric comorbidity is warranted. Certain treatable psychiatric disorders, such as bipolar disorder and posttraumatic stress disorder, are commonly associated with substance use disorders, and appropriate treatment of these disorders may improve both the aggression and the substance use-related outcomes.

Serotonin reuptake inhibitors have shown promise in the treatment of some subtypes of alcoholics. The anticonvulsant mood-stabilizing agents (eg carbamazepine and valproate) can be useful in the treatment of withdrawal syndromes and have shown promise in decreasing impulsiveness and aggressiveness. Psychosocial treatment of the substance use disorder is also important. Interventions focused on parenting skills can be important in breaking the cycle of domestic violence and substance abuse.

Clinical Implications

References

  1. National Center for Injury Prevention and Control, Centers for Disease Control and Prevention. Leading causes of death reports. Available at: http://webapp.cdc.gov/sasweb/ncipc/leadcaus.html.
  2. Evenden J. Impulsivity: a discussion of clinical and experimental findings. J Psychopharmacol (Oxf). 1999;13:180-192.
  3. Coccaro EF, Kavoussi RJ, Trestman RL, Gabriel SM, Cooper TB, Siever LJ. 5-HT function in human subjects: intercorrelations among central serotonin indices and aggressiveness. Psychiatry Res. 1997;73:1-14.
  4. Coccaro EF, Kavoussi RJ, Hauger RL, Cooper TB, Ferris CF. Cerebrospinal fluid vasopressin levels: correlates with aggression and serotonin function in personality-disordered subjects. Arch Gen Psychiatry. 1998;55:708-714.
  5. Coccaro EF. Personality disorder and impulsive aggression. Program and abstracts from the 153rd Annual American Psychiatric Association Meeting, May 13-18, 2000; Chicago, Illinois. Abstract 26A.
  6. Barratt ES, Stanford MS, Felthous AR, Kent TA. The effects of phenytoin on impulsive and premeditated aggression: a controlled study. J Clin Psychopharmacol. 1997;17:341-349.
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  12. Fava M. Depression and anger attacks. Program and abstracts from the 153rd Annual American Psychiatric Association Meeting, May 13-18, 2000; Chicago, Illinois. Abstract 26B.
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  17. Chengappa KNR. Impact of newer antipsychotic agents on violence in psychoses. Program and abstracts from the 153rd Annual American Psychiatric Association Meeting, May 13-18, 2000; Chicago, Illinois. Abstract 26C.
  18. Brady KT. Violent behavior and substance use disorders. Program and abstracts from the 153rd Annual American Psychiatric Association Meeting, May 13-18, 2000; Chicago, Illinois. Abstract 26D.
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