Gabapentin in the Treatment of Aggression Associated With Conduct Disorder

Sir: In this case report, we describe a patient with a DSM-IV diagnosis of conduct disorder resulting in aggression and violent behavior whose symptoms were controlled with gabapentin after he had failed a trial of divalproex sodium. There is one previously published report¹ of gabapentin in the treatment of mania, but we found no cases describing its use in aggression related to conduct disorder.

Case report. Mr. A, a 17-year-old adolescent boy, was admitted to a children's home in September 1997 owing to multiple offenses including endangering the welfare of a minor, resisting arrest, petty larceny, and criminal mischief. He was first seen in psychiatric consultation because of aggressive behavior and physical assault; the last episode involved a police officer. Mr. A gave a history indicative of poor impulse control, indicating “I act first and think later.” He reported getting into altercations that he realized he should have refrained from and that his response to situations was out of proportion to the provocation and was at times even unprovoked. He also gave a history of easy irritability and explosivity. His past psychiatric history revealed one previous psychiatric hospitalization after a fight with the police. Past medical history revealed a closed head injury with loss of consciousness for 4 hours following a fight with the police. There was no history of seizure disorder. He had drunk alcohol twice in his life and had never used drugs. Mr. A had no contact for many years with his biological father. School records from testing done in 1993 indicated a verbal IQ of 95, performance IQ of 108, and a full-scale IQ of 94. His mathematics and English skills were at the seventh- and ninth-grade level, respectively. Legal history was significant for 12 felonies, including armed robbery and drug trafficking, and he had been incarcerated approximately 5 times. Mr. A also admitted to stabbing a sixth grader multiple times. The initial diagnosis was intermittent explosive disorder, with bipolar disorder NOS in the differential diagnosis. Owing to the history of head injury, temporal lobe syndrome cannot be ruled out, despite one normal sleep-deprived electroencephalogram (EEG).

Mr. A underwent a complete medical workup that included laboratory studies, a computed tomographic scan of the brain, and sleep-deprived EEG. All test results were unremarkable. He was started with divalproex, 500 mg twice daily, which was then titrated to a total dosage of 2000 mg in divided dosages (serum level = 91.2 µg/mL), in an effort to address target symptoms such as unprovoked aggression, impulsivity, and explosivity. Because of continuing sleep disturbance, trazodone was added in a dosage of 50 mg at bedtime and was increased to 75 mg. He continued community service at this time and continued to be assaultive to peers and others in an unpredictable fashion. He continued to report racing thoughts and sleep disturbance. He took divalproex for a total duration of 7 months and took the 2000-mg/day dosage for the last 3 months prior to hospitalization. Mr. A developed increasing depressive symptoms and was prescribed fluoxetine, 10 mg daily, but subsequently was hospitalized owing to suicidal ideation stemming from his concern that he was going to spend the rest of his life in prison.

Mr. A returned from the hospital on treatment with a combination of multiple medications, which included gabapentin, 400 mg q.i.d.; risperidone, 2 mg h.s.; bupropion sustained release, 150 mg t.i.d.; and amantadine, 100 mg b.i.d. He was switched to gabapentin owing to lack of response to divalproex. He reported that he was “doing really well,” without any racing thoughts, and his sleep pattern had improved. The discharge diagnosis was major depression without psychotic features and conduct disorder, childhood onset. No further aggressive episodes were reported. Mr. A was tapered off the amantadine and risperidone without any increase in aggression. He had been taking gabapentin for a total of 3 months prior to discharge from the children's home and had been free of aggressive episodes for that time frame.

This case describes a teenager with a DSM-IV diagnosis of conduct disorder who had comorbid diagnoses of bipolar disorder, major depression, and intermittent explosive disorder. Gabapentin was found to be effective when used to treat target symptoms such as unprovoked aggression, impulsivity, and explosivity. His symptomatology was complex, which made the case a diagnostic challenge. In addition to conduct disorder, symptoms included depression, manic-type symptoms, and explosive symptoms. Gabapentin was clearly efficacious in controlling the irritability, mood swings, impulsivity, and aggression. Limitations of this case study are the use of adjunctive medications such as bupropion with gabapentin and fluoxetine with divalproex and the initial use of risperidone with gabapentin.

There is one previous report¹ of gabapentin used successfully in an adolescent manic patient who failed a trial of divalproex. That patient had comorbid attention-deficit/hyperactivity disorder, unlike our patient, who had conduct disorder and a complex comorbid symptomatology. Several reports describe the use of gabapentin in mania in adults.^2–5 We found no reports describing the use of gabapentin in patients with severe conduct disorder. Lithium carbonate, divalproex, and antipsychotics have been used extensively in patients with conduct disorder who have severe aggression.

This case suggests that gabapentin is a valuable option because of good tolerability, safety in overdose, and good symptom control. The pharmacokinetic profile of gabapentin offers several advantages over other antiepileptic agents such as absence of serum protein binding and the absence of hepatic metabolism. It is eliminated unchanged by the kidneys. Drug-drug interactions with other antiepileptic drugs and other medications, such as oral contraceptives, appear nonexistent. In the primary care setting, gabapentin is a relatively safe drug to use because of its safety in overdose and lack of need of frequent blood levels for monitoring (unlike divalproex). In adults, the dosage range of gabapentin is 600 to 4800 mg/day, whereas in children, the suggested dosing is 10 to 30 mg/kg/day given in 3 divided dosages. Controlled studies are needed to further establish these findings.