Successful Multimodality Treatment of Severe Behavioral Disturbance in a Patient With Advanced Huntington’s Disease

Mr. A was a 32-year-old single African American man with advanced Huntington’s disease who was referred to the inpatient unit of the neuropsychiatry service of the Johns Hopkins Hospital from his nursing home for evaluation and treatment of complex behavioral disturbances. These included attempts to escape, assaults, and inappropriate touching of female staff members. Mr. A’s history was obtained from his mother and sister, the nursing home staff, previous psychiatric records, and the patient himself.

Mr. A’s father and three paternal aunts had all been afflicted with Huntington’s disease. His father had first developed motor symptoms in his late 30s and died at age 52. A number of Mr. A’s paternal cousins also had Huntington’s disease. His sister had developed Huntington’s disease in her early teens and died at the age of 28. Mr. A’s two older siblings had not been genetically tested for Huntington’s disease and were asymptomatic at age 34. There was no other known psychiatric or neurological family history.

Mr. A had been born 2 months prematurely and weighed 5 pounds. There were no known residua of the prematurity, and he had developed normally. He was described as a hyperactive child who frequently got into trouble, was known as a class clown, and engaged in theft at an early age. There was no known history of setting fires, cruelty to animals, or running away from home.

Mr. A had dropped out of school after the eighth grade, having been educated to that point in a regular classroom. He had been a poor student academically. After leaving school, he had worked for a number of years in janitorial services, until he developed symptoms of Huntington’s disease and it became impossible for him to work.

Mr. A had lived at home with his mother until 1 year before admission, when his behavioral disturbances had necessitated placement into a nursing home. He was heterosexual but had never had a long-term relationship and had no children. There was no history of smoking, alcohol abuse, or illicit drug use nor was there any history of arrest.

Mr. A had had an inguinal hernia repaired at the age of 6. He had suffered from mild asthma as a child, which he apparently outgrew. He had recently tested negative for HIV. He had no known medication allergies. His medications at admission were 15 mg of flurazepam at bedtime, 2.5 mg b.i.d. of diazepam, 25 mg of doxepin at bedtime, 75 mg b.i.d. of venlafaxine, 200 mg b.i.d. of carbamazepine, 50 mg b.i.d. of quetiapine, 50 mg q.i.d. of chlorpromazine, 1 mg/day of folic acid, 0.5 mg b.i.d. of benztropine as needed, and 1 mg of lorazepam every 4 hours as needed for agitation.

Mr. A had first developed motor symptoms at the age of 15; these were mild abnormal hand and trunk movements. He had been subsequently diagnosed with Huntington’s disease at the age of 20, when his unstable gait led to frequent falls and a neurological consultation. Despite his early symptoms Mr. A had continued to function responsibly at work and at home.

Psychiatric symptoms had been noted at age 24, which was 8 years before admission. According to the family, he had undergone a marked change in personality, becoming shy, withdrawn, and apathetic. He had remained in his room watching television for much of the day. He had not appeared sad nor did he express feelings of sadness. Neither Mr. A nor his family reported any change in his appetite or sleep pattern, but his energy had appeared diminished.

Five years before admission, at the age of 27, his gait instability had become so severe that Mr. A had to stop working. Concurrently, he had developed difficulty feeding himself. He had continued to live at home under his family’s care, spending the majority of his time watching television in his bedroom.

One year before admission, Mr. A had developed auditory hallucinations of people speaking outside his window. He had developed the delusional belief that his body was inhabited by several people, including God’s daughter, and that his food was being poisoned. He had been noted to be religiously preoccupied. He had often wandered out of the house, becoming locked out on a number of occasions. The development of command auditory hallucinations to harm his family had prompted emergency admission to a local psychiatric hospital; he had been discharged to a nursing home because it had been deemed unsafe for him to remain at home.

Over the next year multiple problematic behaviors had developed. Mr. A regularly touched female staff members and residents inappropriately. He frequently masturbated in public. He often was found wandering the halls without clothes. He had frequent falls, often resulting in injury. He usually refused to wear his prescribed protective equipment while walking (a helmet and knee and elbow pads had been prescribed to prevent injury as a consequence of his frequent falls). He also made frequent attempts to escape from the facility. When redirected, he often struck out at staff members. Of note, he was never violent or aggressive outside of demand situations. Neuroleptics (chlorpromazine and quetiapine) and benzodiazepines (flurazepam, diazepam, and lorazepam) had been gradually added to his drug regimen to help control his behavior. The doses ultimately were increased to the point at which Mr. A was nearly continuously sedated. When the doses were lowered to improve his quality of life, his problematic behaviors returned.

Mr. A had been admitted to local hospitals on a number of occasions because of these behaviors. During these admissions he was noted to have visual hallucinations in addition to the described symptoms. A computerized tomography scan of his head was read as showing the absence of caudate nuclei and mild generalized atrophy but no other abnormalities. An EEG could not be interpreted because of motion artifact. Medications prescribed in that year (aside from those listed) included haloperidol, risperidone, valproic acid, and nortriptyline. Despite these multiple medication trials and psychiatric admissions, there was no improvement in Mr. A’s condition. He was then referred to the neuropsychiatry inpatient service for further evaluation.

Mr. A was a thin African American man who was sitting up in bed wearing a helmet. He was awake but only intermittently attentive. Eye contact was poor. There was frequent eye blinking and chin twitching. His speech was slow, quiet, dysarthric, and quite difficult to understand. His answers were generally restricted to one or two words. He stated that he was happy, although his affect appeared to be quite blunted and limited to a restricted range. He said that his energy and appetite were good, and he reported no suicidal or homicidal ideation. He acknowledged auditory hallucinations, but it was difficult to understand his report of their content. He reported no experiences of passivity or delusions. He reported no obsessions, compulsions, or phobias. On the Mini-Mental State Examination (MMSE) (10), he scored 10 of 30, including 0 of 10 for orientation, 0 of 5 for calculation, and 0 of 3 for recall. He scored 3 of 3 for registration, 2 of 2 for naming objects, 3 of 3 for following a three-step instruction, 1 point for reading, and 1 point for repeating a sentence. He lost 2 points because of his inability to write a sentence or copy interlocking pentagons.

On physical examination, his vital signs were found to be normal. He appeared adequately nourished, and his dentition was good. He had marked rigidity in all four extremities. Choreiform movements were present in his trunk and proximal extremities. Occasional hemiballismus was noted. He had poor upward gaze with his right eye and poor lateral and upward gaze with his left eye, but his eye movements were smooth. He was unable to suppress blinks, and his initiation of eye movements was delayed. He was able to protrude his tongue, but other voluntary facial movements were limited. Cranial nerves VII, XI, and XII were otherwise intact, as was his hearing. His strength was rated 4 of 5 and was symmetrical in all four extremities. The results of a sensory examination were normal. His deep tendon reflexes were rated 2+ and symmetrical in the upper extremities and 3+ and symmetrical in the lower extremities. His plantar reflexes were flexor bilaterally. He could stand and walk only with assistance. The remainder of the physical examination was unremarkable.

The initial formulation focused on the fact that Mr. A had advanced Huntington’s disease and a broad array of psychiatric symptoms. The latter were felt to reflect a number of distinct but interrelated syndromes. These included disturbances of behavior (aggression, unwanted touching of others, and wandering), as well as psychosis with auditory and visual hallucinations and persecutory delusions. His cognition was impaired globally, and he also had an impaired ability to sustain a consistent level of attention. There was no evidence of affective disturbance initially. His history and the results of his mental status examination showed clear evidence of delirium, most likely as a result of polypharmacy in a patient vulnerable to delirium due to advanced Huntington’s disease. Although delirium could partially account for his behavioral disturbances, psychotic symptoms, and cognitive impairment, his history reflected the presence of all of these symptoms before exposure to polypharmacy. Given the chronicity of his motor symptoms, he almost certainly had dementia as a result of Huntington’s disease. His disturbed behavior and psychotic symptoms may also have been a primary consequence of brain damage due to Huntington’s disease. We entertained the possibility that he had a psychotic affective syndrome, something that would not have been unusual in a patient with Huntington’s disease (6).

The initial goal was to remove as many medications as possible from Mr. A’s regimen in order to clarify his differential diagnosis and to reach a conclusive formulation of his illness before developing a long-term treatment plan. A workup to rule out any medical complications that might have been exacerbating his condition was undertaken.

At the time of admission, a series of laboratory tests were conducted, including a CBC with differential, an electrolyte panel, tests of liver function, a urinalysis, and measures of levels of thyroid-stimulating hormone, vitamin B₁₂, and folate; the results were found to be normal. His rapid plasma reagin was nonreactive. His trough carbamazepine level was 5.3 mg/liter. An ECG was unremarkable. Brain magnetic resonance imaging revealed small putaminal and caudate nuclei, as well as minimal diffuse cerebral volume loss.

Mr. A’s 6:00 a.m. serum testosterone level was 566 ng/dl (normal range=286–1510); an HIV antibody test was negative. A serum sample was sent for confirmation of the diagnosis of Huntington’s disease (results of which were only available after discharge but confirmed the presence of the expanded trinucleotide repeat, at 65 copies).

Over the initial 5 hospital days, chlorpromazine, quetiapine, doxepin, venlafaxine, and benztropine were tapered completely without complications or discontinuation symptoms. Diazepam and flurazepam were switched to 1 mg t.i.d. of clonazepam, which was reduced to 0.5 mg t.i.d. by hospital day 11. Carbamazepine was also tapered and discontinued by hospital day 11. All of the tapers occurred concurrently.

During the first week in the hospital, Mr. A remained extremely sedated, spending most of the day in bed or in a reclining chair with a restraining tray (to prevent falls); his only activity was eating and occasional masturbation. He was frequently incontinent of urine, and his sleep did not follow a regular pattern. There were no behavioral disturbances during this time. These symptoms were all felt to be consistent with delirium.

With the reduction in polypharmacy, Mr. A’s delirium cleared gradually over time, and several problematic behaviors reemerged. There were multiple episodes of grabbing female staff members, public masturbation, and attempts to escape. Mr. A often walked without his protective equipment and, when redirected, would often refuse or attempt to strike the redirecting staff member. As more days passed, psychomotor agitation, rapid, slurred speech, and jogging in the hallway became prominent symptoms. Mr. A became suspicious that his food was poisoned and greatly reduced his caloric intake. He frequently refused to take his medications. Of note, he became completely alert and continent. His sleep pattern returned to normal.

At this point we felt that Mr. A’s delirium had disappeared and that he was in a manic episode. We postulated that his behavioral disturbances were now being exacerbated by the mania, although according to his history, they had clearly preceded the onset of psychomotor agitation, pressured speech, paranoia, or generalized hyperactivity, all of which were now present. There was no evidence of any complicating medical problems, and he did not have an elevated serum testosterone level (which might have explained his hypersexuality). He clearly had advanced dementia, which could now be appreciated as distinct from his delirium, as evidenced by his continued memory difficulties in the absence of a fluctuating level of consciousness.

There was now sufficient information to formulate a comprehensive multidisciplinary treatment plan. We initiated antimanic pharmacotherapy with carbamazepine and thioridazine, watching carefully for the development of oversedation or delirium. Doses were ultimately increased to 200 mg of carbamazepine in the morning and 300 mg at bedtime and 20 mg t.i.d. of thioridazine. Treatment with medroxyprogesterone acetate was initiated to help reduce Mr. A’s sexual drive and hypersexual behavior, as well as to reduce his aggression.

Formulation of his medication regimen was guided by a thorough review of previous medication trials, a desire to minimize side effects, and the sparse literature available to specifically guide our decisions. Thioridazine was chosen for its sedating properties, given Mr. A’s manic symptoms and his lack of benefit from quetiapine, risperidone, haloperidol, and chlorpromazine. These considerations were balanced against the acknowledged risk of delirium with thioridazine; certainly this agent would not have been a first-line choice, particularly in a patient with a complex neurological condition. Clonazepam was chosen because of its intermediate-length half-life and our desire to avoid agents with either a very short or very long half-life, such as alprazolam and diazepam, respectively. Carbamazepine was selected as the mood stabilizer because of concern about Mr. A’s ability to tolerate lithium, especially with his fluctuating food and fluid intake. Moreover, the available medical records indicated that Mr. A had been treated with valproic acid with unclear benefit. The use of medroxyprogesterone to reduce his sexual drive was supported by early data regarding antiandrogen therapy in the treatment of inappropriate sexual behavior in patients with other forms of dementia (11), although we found no specific data regarding such therapy for patients with Huntington’s disease.

Within a number of days of initiating these medications, there was a significant reduction in Mr. A’s symptoms of paranoia, pressured speech, and psychomotor agitation. However, his problematic behaviors continued essentially unchanged. Consultations from physical and occupational therapy services were obtained regarding the use of protective equipment and gait-assisting devices and the development of bathing and eating protocols to maximize independence, minimize injuries, and standardize Mr. A’s daily care.

At this point, the focus of treatment turned toward behavior management, through the use of applied behavioral analysis (12). A consultation was obtained from the behavioral psychology division of the Kennedy Krieger Institute. We were advised to initiate a period of detailed data collection for behavioral analysis. The goal was to identify the precise context and time course of Mr. A’s behavioral disturbances, the salient reinforcers of this behavior, time spent in various activities, as well as the usual staff reactions and their effects. Detailed information was obtained from the inpatient nursing staff, the nursing home staff, and Mr. A’s family, in addition to numerous hours of direct observation of Mr. A by the behavioral psychology team. An activity monitoring system was implemented to document his activities every 15 minutes, including the specific times and contexts of any of the problematic behaviors.

After 5 days of data collection, the following preliminary observations were made: Mr. A’s problematic behaviors occurred most often in demand situations, such as when he was asked to take medication or to interrupt a pleasant activity, such as walking or watching television. The touching of female staff members tended to occur during bathing or dressing. There was no clear pattern to his public masturbation. His preferred activities were identified as watching television, eating snack food, and walking.

A complex behavior modification plan was devised and implemented. The first component was the development of a consistent and highly structured daily schedule for Mr. A. This schedule was placed in the line of sight from his bed and reviewed with him regularly. Activities he preferred would be written into the schedule as frequently as possible, and less preferred activities (e.g., taking medications) would always be followed by preferred activities. Transitions from one activity or task to another would be preceded by notifications from the staff ahead of time. The goal was to minimize surprise or change and to create a situation in which compliance with required activities led to consistent rewards.

The second aspect of the behavioral plan was the development of a differential reinforcement schedule, that is, a structured system to ensure that desired behaviors were reinforced and undesired behaviors were not inadvertently reinforced. Initially, reinforcement was to be provided at 1-hour intervals only if Mr. A adhered to a few clear rules:

1. No aggressive behavior toward staff or other patients.

2. No inappropriate touching of staff or other patients.

3. Medications must be taken as prescribed.

4. Walking must be performed with protective equipment (helmet, shoes, and knee and elbow pads) in place.

5. A break from walking should be taken if he was so tired that he started falling.

6. Masturbation must occur only in his room.

Basic principles of behavior modification were made explicit to the inpatient staff as part of the behavior plan. For example, each reinforcement was to be accompanied by an explanation of why Mr. A was receiving it, as well as generous verbal praise. Mr. A was to be given the option of choosing which reward he wanted (e.g., candy versus chips versus soda), and, even if he did not make a choice, one should be provided anyway. If he did not earn the reward, then a brief explanation of why he was not getting it should be provided. Inappropriate behavior was to be “blocked,” that is, interrupted with a brief reprimand but with as little attention as possible given to the behavior. Opportunities for success were to be maximized.

Demand situations were to be preceded by a small reinforcer and an explanation of what was about to occur and of what was expected from the patient. If Mr. A successfully complied with the demand, more reinforcement and praise should be given. If he refused the request, standard unit rules were to be implemented to deal with the situation.

Finally, it was recommended that a staff member be individually assigned at predetermined times during the day (on Mr. A’s schedule) to walk with him. This was one of his preferred activities during the day and the one that frequently generated conflict as a result of the staff’s concerns about his safety and his desire to walk ad lib.

The behavior plan in its entirety was documented in Mr. A’s chart in a typed note and reviewed in detail with the entire staff working directly with Mr. A. The detailed monitoring of his behavior continued so that the success of the plan could be assessed and changes made when necessary.

Five days after the implementation of the behavior modification plan (which was 2 weeks after the initiation of antimanic medications), Mr. A’s behavior improved dramatically. He began to initiate the wearing of his protective gear, and when he failed to do so and was reminded, he generally complied by putting the gear on. He also became completely compliant with taking medications. Initially, it was necessary on a few occasions to have security officers present at the time of these requests, but the need for this intervention was short-lived. His aggressive behavior was completely extinguished, and Mr. A also was able to comply with restricting masturbation to his room. The touching of female staff members diminished significantly with the initial plan but was not extinguished, and some adjustments to the plan were made. As noted, Mr. A had been given medroxyprogesterone acetate to help reduce his sexual drive somewhat. The reinforcement interval was spaced gradually to every 3–4 hours.

Within 2 weeks of initiating the behavior plan, Mr. A was prepared for discharge to the nursing home facility. The nursing home staff visited the inpatient unit on several occasions to be trained in the implementation of the behavior plan. Mr. A was discharged to the nursing home after a 32-day hospital stay. At discharge he was walking well and had only one or two falls per day. His medication regimen at discharge was 200 mg of carbamazepine in the morning and 300 mg at bedtime (trough level=7.5 mg/liter), 20 mg t.i.d. of thioridazine, 0.5 mg t.i.d. of clonazepam, 5 mg/day of medroxyprogesterone acetate, 1 mg/day of folic acid, and a daily multivitamin.

Mr. A did well at the nursing home for a number of months; there was continued successful implementation of the behavioral plan. Approximately 4 months after discharge, his condition worsened again, without any obvious precipitant. Mr. A made frequent attempts to escape, exhibited public masturbation and nudity, walked without protective gear, and had violent outbursts when redirected by staff members. Haloperidol, 5 mg bi.d., was substituted for thioridazine by the nursing home physician, and Mr. A received 1–2 mg/day of lorazepam, both orally and intramuscularly. He was referred for readmission to our unit.

Mr. A was awake and minimally interactive and appeared confused. He was unable to sit unassisted without falling over. His eye contact was minimal. His answers were quiet, slow, and generally monosyllabic; there was significant latency. He stated that his mood was “okay,” but his affect appeared quite constricted. He reported no suicidal or homicidal ideation. It was difficult to assess hallucinations or delusions. His MMSE score was 0 of 30. The results of a neurological examination were not appreciably different from the one documented previously.

As before, routine laboratory tests included a CBC, an electrolyte panel, tests of liver function, a urinalysis, a measure of thyroid-stimulating hormone level, and a chest radiograph; all results were normal. His trough serum carbamazepine concentration was 7.8 mg/liter. His serum testosterone level at 7:00 a.m. was 388 ng/dl.

The initial impression was again one of delirium, likely the result of polypharmacy; the high dose of lorazepam was the most proximal agent. The most likely scenario was that Mr. A had had a breakthrough of manic symptoms leading to a worsening of behavior and increased medication use, a deterioration in the implementation of the behavior plan over time leading to a reemergence of his symptoms, or a combination of these two possibilities.

Mr. A was readmitted to the neuropsychiatry service inpatient unit with the drug regimen previously described. His clonazepam dose was tapered to 0.25 mg at bedtime. His medroxyprogesterone acetate dose was increased to 10 mg/day given that his testosterone level was still within the normal range. The behavior modification plan previously formulated was reinstituted. When it became apparent that Mr. A was experiencing auditory hallucinations, his haloperidol dose was increased to 7.5 mg b.i.d.

As during his first hospitalization, Mr. A’s behavior improved significantly with strict implementation of the behavior plan, with the exception of ongoing attempts to touch female staff members during direct care. Once the behavior plan was in place, his aggression, public masturbation, attempts to escape, and walking without protective gear stopped. The inpatient unit staff again worked with the nursing home staff to improve implementation of the behavior plan in the nursing home environment. Mr. A was discharged to the nursing home after a 13-day hospitalization. His discharge medications included 200 mg of carbamazepine in the morning and 300 mg at bedtime, 7.5 mg b.i.d. of haloperidol, 0.25 mg of clonazepam at bedtime, 10 mg/day of medroxyprogesterone acetate, 1 mg/day of folic acid, and a daily multivitamin.