Treatment of Sudden, Intense Rage Reactivity After Minor Head Injury

This is a case of a man with Down syndrome whose recent brain injury likely caused him to regress to a rage state he had experienced when he was younger. Some details have been changed to preserve anonymity.  We invite your comments below. Dr Ankenman will review your responses and give his feedback in coming weeks.

CASE VIGNETTE

Lionel, a 24-year-old man with Down syndrome, had some rage episodes during adolescence. For the past 4 years, he had exhibited no problems with rage behavior; his life was stable and he was employed at a local factory. He recently sustained a blow to his head, causing him to be unconscious for 18 hours. On awakening at the hospital, his neurological examination showed nonspecific changes. Electroencephalography showed slowing over the temporal areas-unchanged from the tracing made 3 years earlier. Within 48 hours, findings from the patient’s neurological examination were within normal range. A cerebral contusion was diagnosed, and he was discharged.

Two weeks after the accident, one of his parents contacted the discharging neurologist to report that Lionel had experienced several episodes of severe, frenzied rages. The parent commented, “The episodes are kind of like the ones he used to have when he was 15, except they are even more intense and they do not last very long.” The mother, an emergency department nurse, had recorded his blood pressure at 160/90 mm Hg and his pulse rate over 120 beats per minute during one episode.

Question to consider

Read the question below and select the best answer. For the answer, click here.

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Answer:D. Initiate low-dose propranolol therapy

Discussion

The use of neuropsychiatric medications that directly affect adrenal function has been reported irregularly since the early 1970s, when propranolol was introduced. The therapeutic use of propranolol to control rage behavior after brain trauma was well described in 1977 by Frank Elliott, MD,¹ former Chief of the department of neurology of the University of Pennsylvania.

Dr Elliott selected 10 patients who had sustained traumatic brain injury. All 10 patients had normal brain function before the injury but began demonstrating episodes of rage reactivity after the injury. The paper was unique among the literature regarding the effect of -blocker therapy on behavior. It consisted of a definable group of subjects who had the same diagnosis and similar levels in rage reactivity. All 10 patients continued to experience rages with anticonvulsant (phenytoin) treatment. Therapy with typical antipsychotics also had no effect. However, rage behavior was successfully treated with propranolol at a relatively low dose. The propranolol was given for a year, then tapered off. Five of the patients remained off propranolol, without recurrence of rage episodes. The 5 others had recurring symptoms that responded well when -blocker therapy was restarted.

Elliott’s work may not have been a double-blind crossover study, but symptom resolution of 100% should not be ignored. Early researchers considered propranolol the best -blocker for rage symptoms-it was believed to affect norepinephrine activity in the brain because of its fat solubility. Later research by Ratey and colleagues² showed that nadolol, a water-soluble -blocker, also could stop rage behavior. The researchers theorized that nadolol muted the effects of excess adrenaline, thereby reducing the adrenergic “crisis signals” being sent by the body to the brain.

To date, there has not been adequate research to demonstrate with certainty the specific action by which -blocking medication so effectively reduces or resolves rage episodes. Yet -blockers are effective in a high percentage of patients whose rage behavior is similar to that described in the patients from Elliott’s study: intense rages that come on suddenly, often triggered by minor situations, leaving individuals apologetic or confused about why they became so upset, and characterized by extremely high pulse rates of over 120 beats per minute. These symptoms all point to -adrenergic overreactivity or a -adrenergic “fright-flight” crisis state.

Other studies show that there are patients whose rage behavior does not improve or even worsens with propranolol treatment.³ Such patients have rage episodes accompanied by other, more serious characteristics (eg, threatening behavior, a “psychotic look” in the eyes, memory loss of some or all of the events). Although this type of rage is not well described in the medical literature, it seems to be related to vasoconstriction, which would be exacerbated by propranolol treatment, and the substitution of a ₁-selective medication is far more effective.

More research to identify how adrenaline activity can affect behavior is needed. In particular, there should be a study dealing with rage after brain injury. Additional insight into this rather uncommon problem could open the way for better understanding and treatment of violence and rage in a wide scope of conditions.

Outcome

When Lionel was a teenager, his anger upsets occurred primarily in response to frustration or unexpected changes to his daily routine. I call this state the “-adrenergic rage state.” Individuals with Down syndrome who have rage behavior almost always have -adrenergic rage. Lionel had matured and learned how to control his impulses. The brain injury produced some type of regression in his -adrenergic reactivity. Treatment with a -blocker stopped the source of the rage reactivity and helped the patient regain his earlier, more mature, control.

References:

References1. Elliott FA. Propranolol for the control of belligerent behavior following acute brain damage. Ann Neurol. 1977;1:489-491.
2. Ratey JJ, Sorgi P, O’Driscoll GA, et al. Nadolol to treat aggression and psychiatric symptomatology in chronic psychiatric inpatients: a double-blind, placebo-controlled study. J Clin Psychiatry. 1992;53:41-46.
3. Silver JM, Yudofsky SC, Slater JA, et al. Propranolol treatment of chronically hospitalized aggressive patients. J Neuropsychiatry Clin Neurosci. 1999;11:328-335.