Vol. 1, No. 4 , 1995, Page 1&2

SIDE EFFECT OF SEIZURE DRUG: REDUCED AGGRESSION

The drug carbamazepine (commonly known by the brand name Tegretol) is a highly effective treatment for some forms of seizures. But research suggests that the drug may have another beneficial effect: the reduction of aggression in neurologically disordered individuals without overt seizure disorders.

Recently researchers Marc Hillbrand and John Young reported the case of a sexual offender with a history of violent behavior and brain damage caused by ingestion of large amounts of LSD. When the researchers administered carbamazepine to the man (whose initial EEG was reported to be "essentially normal"), he reported "an almost immediate calming effect," an increase in concentration, and a reduction in depressive symptoms. Hillbrand and Young say the staff at the subject's forensic hospital "documented a markedly reduced frequency of angry outbursts," and noted that the patient was calmer and better able to tolerate frustration. These effects were reversed when the subject stopped taking the drug, and reoccurred when treatment was resumed.

The researchers administered the Wisconsin Card Sorting Test (WCST) -- often used to evaluate frontal lobe functioning -- to the subject before and during treatment as well as in between treatment periods, and found that WCST test scores improved markedly during drug therapy and worsened when treatment was stopped. "This pattern," Hillbrand and Young say, "provides support for the literature documenting the anti- aggressive effect of carbamazepine," and suggests that the drug may help normalize frontal lobe functioning.

Many studies corroborate findings

Young and Hillbrand recently reviewed studies of the anti-aggressive effects of carbamazepine. They cite numerous findings, including:

-- A 1981 study by de Vogelaer, who treated twenty aggressive, non-epileptic psychiatric patients with carbamazepine in a double-blind crossover study. De Vogelaer reported a 73 percent improvement rate with carbamazepine compared to placebo, and said many subjects were able to stop taking other behavior-controlling drugs.

-- A 1982 study by Hakola and Laulumaa, who found that adding carbamazepine to the neuroleptic drugs being taken by very violent, psychotic female patients dramatically reduced their aggression.

-- A 1984 report by Mattes, who administered carbamazepine to 34 aggressive patients with a range of disorders. Treatment led to a marked reduction in the severity of physical assaults by the patients.

-- A 1987 study by Patterson, who reported that carbamazepine therapy led to significant and sustained reductions in assaultive behavior in eight aggressive patients with known organic disorders.

--A 1989 study by Foster et al., which found that assaultive male forensic patients treated with carbamazepine became less aggressive. In addition, the patients exhibited cognitive improvements which persisted even after drug therapy ended.

-- A 1990 report by Barreira et al. on 27 aggressive state hospital patients given large doses of carbamazepine. Twenty-three of the patients responded positively to the drug.

-- A 1990 study by Mattes et al. of aggressive individuals diagnosed as having attention deficit disorder or intermittent explosive disorder. Researchers found that carbamazepine was as effective in controlling aggression as propranolol, a drug commonly used for that purpose.

The researchers caution, however, that in one study of boys aged 10 to 16 years, with diagnoses of conduct disorder and/or attention deficit hyperactivity disorder and aggressive behaviors, all subjects reacted with increased aggression when carbamazepine was administered. This finding was contradicted by a study which noted improvements in a similar group of children given the drug.

The researchers conclude that "carbamazepine is effective in lowering aggression across varied diagnostic groups." They express concern about using the drug "for the purpose of merely quieting aggressive chronic public sector patients," saying that "rather, it is to be hoped that clinical improvement would lead to the enjoyment of a better quality of life" for aggressive individuals.

While carbamazepine may prove to be an effective treatment for violent behavior, the drug can cause serious side effects including blood disorders, cardiac problems, thyroid dysfunction, respiratory problems, and liver changes. Thus, patients taking the drug must be monitored carefully.

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"Wisconsin Card Sorting Test performance during carbamazepine monotherapy of aggressive behavior," Marc Hillbrand and John L. Young, Neuropsychiatry, Neuropsychology, and Behavioral Neurology, Vol. 8, No. 1, 1995, pp. 61-63. Address: Marc Hillbrand, Whiting Forensic Institute, P.O. Box 70, Middletown, CT 06457.

--and--

"Carbamazepine lowers aggression: a review," John L. Young and Marc Hillbrand, Bulletin of the American Academy of Psychiatry Law, Vol. 22, No. 1, 1994, pp. 53-61. Address: John L. Young, Whiting Forensic Institute, Box 70, Middletown, CT 06457.

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