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Practical psychopharmacology: drug treatment for impulsive aggression. (Psychopharmacology).

Although it is not a formal diagnosis, impulsive aggression has spurred substantial research and attracted clinical attention in recent years, and effective therapeutic strategies have begun to emerge.

"Impulsive aggression is a core symptom domain that cuts across a variety of neuropsychiatric conditions and contributes to public health problems," said Dr. Eric Hollander, director of clinical psychopharmacology and of the compulsive, impulsive, and anxiety disorders program at Mount Sinai Medical Center, New York.

While impulsive aggression is the hallmark of one diagnosis (intermittent explosive disorder), the behavioral disturbance often figures prominently in bipolar disorder, cluster B personality disorders, impulse-control disorders, attention-deficit hyperactivity disorder, substance-use disorders, posttraumatic stress disorder, and autism. It is also associated with a heightened risk of suicide.

Generally, impulsivity represents the inability to match behavior to context--a failure of the unconscious process by which a potential action is checked against memory and environment en route to a conscious decision. "It's a pattern of behavior without reflection," according to Dr. Alan C. Swann, professor of psychiatry and behavioral sciences at the University of Texas, Houston.

The aggressive manifestation characteristically occurs as an overreaction to a minor provocation and is accompanied by disinhibition; a violent response to a perceived intrusion, insult, or frustration is one example. In contrast to predatory aggression, this behavior is sudden, not premeditated, and is enacted without regard for consequences, instead of in the service of secondary goals such as control or financial gain.

"These people are typically bewildered, puzzled, and regretful about their behavior," Dr. Swann said. "They often know better but can't benefit from that knowledge." Individuals who manifest this behavior are likely to act impulsively in other ways as well.

There is growing evidence that specific neurocircuitry and neurotransmitter dysfunctions underlie impulsive aggression in diverse diagnostic contexts. The most prominent dysfunction, said Dr. Hollander, is an apparent deficit in orbitofrontal activity, attenuating circuits that normally "put the brakes on primitive limbically driven impulses."

Neurochemically, deficits in serotonergic systems have been linked by animal and human studies to increased impulsivity and aggression. But serotonin is not the whole story: Norepinephrine, dopamine, and [gamma]-aminobutyric acid also appear to modulate, facilitate, or inhibit impulses, he said.

"We can't medicate predatory aggression," said Dr. Jorge Armenteros, director of pediatric psychopharmacology at the University of Miami. "But we have a good chance of helping impulsive aggression."

Controlled studies and clinical experience suggest that three classes of drugs-- mood stabilizers, selective serotonin reuptake inhibitors (SSRIs), and atypical neuroleptics--are likely to be useful.

In choosing among them, "the more severe the behavioral disturbance, the more the balance tends to shift in favor of a mood stabilizer," Dr. Swann said. Valproate and lithium are best supported by research, with a fair amount of data showing efficacy for carbamazepine as well.

Clinical experience suggests that these drugs should be used as they are in bipolar disorder, probably on the low side of the dosage range. "Tolerability and compliance are very important, in that treatment will be long term," he said. "This is not the time for vigorous valproate loading."

An SSRI may be a better first choice when the aggressive response to provocation is less rapid-fire and where there appear to be elements of compulsivity and difficulties with self-control, he said.

When impulsive aggression occurs in the context of posttraumatic stress disorder, an SSRI might well be the first choice, with valproate a better alternative if the aggression is particularly severe, Dr. Swann said.

Dr. Hollander considers a "diagnostic treatment hierarchy" in choosing medication. If symptoms or a family history suggests bipolarity, he opts for a mood stabilizer, adding an SSRI if necessary. In the absence of those factors, particularly if anxiety or depression is marked, he would likely start with an SSRI.

A "sizable subgroup" of patients may worsen on SSRIs, he cautioned.

There are fewer data to support the use of atypical antipsychotics, but these too have been effective--in modest doses--even in the absence of paranoia or psychosis. And for many difficult cases, combination treatment is indicated, Dr. Hollander said.

Benzodiazepines should be avoided. "They can be associated with disinhibited affect and severe behavioral dyscontrol," Dr. Hollander said.

In treating impulsive aggression in children and adolescents, Dr. Armenteros most often chooses an SSRI--usually citalopram because of its serotonergic specificity. "We always start at a low dose, 10 mg, and titrate up by no more than 10 mg/wk to as high as 40 mg."

He may prescribe an atypical antipsychotic--the data are best for risperidone--when there is some indication of psychosis or the SSRI alone is not sufficient. This too is given at low doses, for example, beginning at 0.5 mg of risperidone and going up by 0.5 mg weekly. "We've found that we can accomplish what we need to below 2 mg/day, for the most part."

In attention-deficit hyperactivity disorder, aggression often resolves, along with focusing and concentration difficulties, with standard psychostimulant therapy. If it does not, an SSRI or antipsychotic may need to be added, Dr. Armenteros said.

While pharmacotherapy is necessary for impulsive aggression, it is frequently not sufficient, Dr. Swann cautioned. "Successful treatment usually requires nonpharmacologic strategies as well; they work synergistically."

Many patients report that medication gives them "the subjective sense of a split second to reflect whether to carry out behavior--an opportunity to think: 'Is it worthwhile?'" Dr. Swann said. Psychotherapy may be essential in helping patients overcome the mental habits of a lifetime to use that opportunity. "They have to learn the ability to reflect, to be more future oriented," he said. By and large, structured approaches, particularly variants of cognitive-behavioral therapy are most helpful in encouraging these adaptations, Dr. Swann said.
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Author:Sherman, Carl
Publication:Clinical Psychiatry News
Geographic Code:1USA
Date:Sep 1, 2002
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