Disinhibition Due to Disruption of the Orbitofrontal Circuit Treated Successfully With Carbamazepine: A Case Series

Our patient is a 57-year-old Caucasian man with a history of seizure disorder treated with levetiracetam, 500 mg p.o. b.i.d., and valproic acid, 500 mg p.o. b.i.d. Prior to hospitalization, he was living at a long-term care facility due to poor medication compliance. He was brought to the emergency department after becoming extremely agitated with the facility staff.

Computerized tomography (CT) of the head revealed a lacunar infarct of the left internal capsule which was not seen on a CT performed 2 months prior. His blood alcohol level was 0.0 on admission. A normal awake EEG did not demonstrate slowing or epileptiform activity. Physical examination and laboratory data were unremarkable except for a temperature of 101.8°F and a WBC count of 12.5K/mm ³, respectively. He was empirically treated with ceftriaxone and his fever and WBC count attenuated, but he continued to be agitated. The agitation was treated by physical restraints and lorazepam, 1 mg i.v. every 4 hours as needed, until we were consulted 5 days later.

The patient also had several instances of sexual disinhibition, in which he attempted to masturbate in the presence of hospital staff. Our service was consulted at this time.

Our initial evaluation was complicated by the patient’s disinhibition, and unfortunately a “baseline” cognitive examination could not be performed. He was oriented only to person. The patient denied hallucinations or delusions.

He was initially treated with aripiprazole, 9.75 mg i.m. b.i.d. for 12 days, which did not stabilize his behavior. Subsequently, aripiprazole was discontinued in lieu of carbamazepine, 200 mg t.i.d., 17 days after he was initially admitted. His carbamazepine levels were 10, 9, and 7 mcg/ml, at weeks 1, 2, and 4, respectively. This was also the maintenance dosage for this patient. Two days after beginning treatment with carbamazepine, the staff was able to successfully remove his restraints. There were no further behavioral problems and his mental status gradually improved. The patient initially scored a 15 on the disinhibition section of the Neuropsychiatric Inventory, 4 but was discharged with a score of 2. By discharge, our patient was oriented times three and was able to recall three out of three words immediately and at 3-minute recall, but his working memory continued to be poor. He was discharged on carbamazepine, and at 2-month follow-up continued to be behaviorally stable.

Our patient is a 42-year-old white male who was admitted to the hospital status-post a closed head injury. A brain CT scan indicated a left frontoparietal subdural hematoma with evidence of subarachnoid hemorrhage and midline shift. After neurosurgical intervention, our patient’s condition stabilized, and a repeat brain CT scan indicated no new hemorrhages.

Behaviorally, our patient’s hospitalization was characterized by disinhibition, starting 2 weeks after admission. He scored a 16 on the disinhibition section of the Neuropsychiatric Inventory, including self-removal of his small bowel feeding tube, requiring intermittent restraints and sedation. Additionally, he was sexually inappropriate and verbally abusive toward staff, which interfered with his rehabilitation. Our team was consulted at this time.

On initial evaluation, our patient denied dysphoria, psychoses, or suicidal/homicidal ideation. Cognitively, our patient was oriented times one, his attention span was grossly impaired and while he could recall three out of three words immediately, on delayed recall he was unable to list any of the three words, even with cues.

Our patient was started on a treatment of carbamazepine, at the time of the initial consultation, two days after admission. His treatment started with carbamazepine, 200 mg p.o. b.i.d., and 5 days later the dosage was increased to maintenance of 400 mg p.o. b.i.d. Blood levels ranged from 6–7 mcg/ml. The result was a rapid decrease in his disinhibition and aggressiveness, such that he was participating appropriately in rehabilitation within 4 days of initiating carbamazepine; however, after 10 days of gradual hyponatremia, carbamazepine was discontinued as his medical team felt that carbamazepine was inducing syndrome of inappropriate anti-diuretic hormone secretion. Three days after discontinuing carbamazepine, aggressive and disinhibited behavior returned. After consultation with his primary care team, carbamazepine was restarted at 400 mg p.o. b.i.d., along with demeclocycline and free water restrictions to maintain sodium levels within normal limits. From a behavioral vantage point, his disinhibited behavior normalized after 2 days of carbamazepine treatment. Interestingly, our patient’s carbamazepine level after 2 days was subtherapeutic at 3 mcg/ml. After an additional 2 days, his carbamazepine dosage was increased to 300 mg p.o. t.i.d., which was his discharge dosage. His discharge carbamazepine serum level was 8 mcg/ml level. Our patient’s final disinhibition section score on the Neuropsychiatric Inventory was 2. Unfortunately, we were unable to follow-up.

Our patient is a 59-year-old white female who was admitted to the hospital for a subarachnoid hemorrhage involving the left anterior cerebral artery status-post aneurysm rupture. After coiling of the lesion, she had rebleeding. Her past medical history is significant for hypertension. She had no prior psychiatric history, although described as an “introvert” by the family prior to the subarachnoid hemorrhage. Her medications on admission included lisinopril.

Two weeks following rupture, we were consulted due to “bizarre behavior.” She began to develop signs of disinhibition, with inappropriate laughter, distractibility, and “elated” mood. Her physical examination was unremarkable except for right-sided hemiparesis with hyperactive ([3/4]) reflexes and ataxia.

On mental status examination, our patient had a notably elevated mood. She was significantly disinhibited verbally, with inappropriate laughter and sexual innuendos. The patient scored a 12 on the disinhibition section of the Neuropsychiatric Inventory. Cognitive examination was unremarkable except for a poor attention span. She denied psychoses or suicidal/homicidal ideation.

Serologic and urine evaluations were within normal limits. An EEG showed no generalized slowing or seizure activity. A CT scan of the brain demonstrated evidence of subarachnoid hemorrhage over both cerebral convexities with right being greater than the left. Additionally, right frontal subcortical white matter infarcts were noted.

Carbamazepine treatment was started at 200 mg p.o. t.i.d., and after 3 days was increased to 400 mg p.o. b.i.d. Her carbamazepine serum level after 5 days was 7 mcg/ml. After 1 week of carbamazepine therapy, our patient scored a 1 on the disinhibition section of the Neuropsychiatric Inventory. She remained in the hospital for an additional 3 weeks treated with carbamazepine, 400 mg p.o. b.i.d. Her carbamazepine serum level at discharge was 5 mcg/ml, and her carbamazepine dose was 400 mg p.o. b.i.d.

On 3-month follow-up, according to the nursing home staff, the patient’s carbamazepine was discontinued after 2 months at the nursing home. They reported that 1 month after the carbamazepine had been stopped, the patient no longer demonstrated sexual and verbal disinhibition.