Psychosomatics 47:70-72, January-February
doi: 10.1176/appi.psy.47.1.70
© 2006 Academy of Psychosomatic Medicine
Quetiapine in the Treatment of Behavioral Disturbances in Patients With Huntington’s Disease
Menekse Alpay, M.D., and
Walter J. Koroshetz, M.D.
Received March 17, 2005; accepted June 25, 2005. From Massachusetts General Hospital, Dept. of Psychiatry, Boston, MA (MA), and Massachusetts General Hospital, Dept. of Neurology, Boston, MA (WJK). Address correspondence and reprint requests to Dr. Alpay, Dept. of Psychiatry, Massachusetts General Hospital, Boston, MA. e-mail: malpay{at}partners.org
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ABSTRACT
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The effect of quetiapine (an atypical antipsychotic with minimal extrapyramidal side effects) on motor as well as behavioral symptoms was studied in five consecutive patients with Huntington’s disease in a long-term facility. Improvement of behavioral symptoms (i.e., psychotic symptoms, agitation, irritability, and insomnia) without worsening of motor functioning were noted.
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INTRODUCTION
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Huntington’s disease is an autosomal dominant disorder that results from excessive repetition of the trinucleotide sequence CAG (cytosine-adenine-guanine) in the Huntington’s disease gene on the short arm of Chromosome 4.1 Progressive atrophy and gliosis of the caudate nucleus is the major neuropathologic finding, but global degeneration occurs with disease progression.2 Patients usually present with choreiform involuntary movements, cognitive decline, and behavioral disturbances.3
Prevalent in 3%–20% of Huntington’s disease (HD) patients, psychotic presentations range from poorly systematized paranoia and isolated delusions to florid psychotic states resembling schizophrenia.4 Behavioral disturbances, specifically psychosis and agitation, are the main reason for patients’ institutionalization.5 Agitation and irritability in this population often require antipsychotic treatment when other agents (e.g., antidepressants, benzodiazepines, mood stabilizers) fail. Conventional (typical) dopamine-blocking agents worsen motor symptoms in patients with HD and other movement disorders.6 Because nonconventional (atypical) antipsychotic agents have a reduced probability of causing extrapyramidal side effects (EPS), these newer medications are preferred in the HD population.7–9 One of these atypical agents, quetiapine, has been used successfully to treat psychosis in patients with Parkinson’s disease.10 In this article, we present results for five patients with HD and psychosis or agitation who were successfully treated with quetiapine.
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Case Reports
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Five consecutive HD patients with behavioral problems in a long-term facility were seen by a team of a neurologist and a psychiatrist and were prescribed quetiapine. The follow-up visits were made monthly for 2 months by the same clinicians.
Case 1
Mr. A was a 40-year-old man with HD, admitted to a long-term facility for chronic care. He carried diagnoses of organic personality disorder, dementia due to HD , and coronary artery disease (CAD), complicated by one myocardial infarction (MI). When he was first seen by our service, he had significant chorea, dystonic posture, gait difficulties, and severe dysarthria. He was fully dependent on staff for completion of activities of daily living (ADLs). He was episodically aggressive, undressed in hallways, paced, and wandered. He was taking lorazepam 1.5 mg twice daily, chlorpromazine 50 mg daily, haloperidol 2 mg twice daily, carbamazepine 1,400 mg daily (serum level: 11), sertraline 75 mg daily, and trazodone 25 mg at bedtime. Initial pharmacologic manipulations, including haloperidol and chlorpromazine, were ineffective in quelling impulsivity and aggression. Therefore, he was weaned off haloperidol and chlorpromazine, and begun on quetiapine. His behavior stabilized within 2 months on 300 mg daily without worsening of his voluntary or involuntary movements.
Case 2
Mr. B was a 40-year-old man who was diagnosed 10 years previously with HD. He had been in long-term psychiatric facilities for severe agitation, physical aggression, and psychotic symptoms for many years. Despite good behavioral control, he was admitted to a long-term facility for worsening dementia on haloperidol 8 mg daily. He was fully dependent on staff for performance of ADLs. Cooperative and pleasant, he had severe dysarthria, dyspraxia, motor impersistence, and stiffness; he was neither agitated nor psychotic. Because of severe dystonic posture and gait difficulties, his haloperidol was gradually decreased, and quetiapine was begun. On haloperidol 0.5 mg twice daily and quetiapine 125 mg twice daily, gait and tone improved, and he was much more mobile. However, he became agitated and wandered, requiring constant observation. When quetiapine was increased to 300 mg twice daily, agitation subsided within 2 months without worsening gait problems and stiffness.
Case 3
Ms. C was a 34-year-old woman with diagnoses of HD , obsessive-compulsive disorder (OCD), and depression, admitted to a long-term care facility with worsening dementia. In addition to poor memory, she had obsessive thinking about "unmet" needs and compulsive behavior manifested as repetitive changing of her clothes and hoarding of other patients’ belongings and trash. She was restless, anxious, and paced constantly. Haloperidol 5 mg per day produced no improvement, and, on 10 mg, her gait and posture became increasingly dystonic. She was also given clomipramine 100 mg daily for OCD-like symptoms, without improvement. Therefore, both haloperidol and clomipramine were stopped. She had worsening restlessness and pacing and decreased sleep and appetite. Quetiapine was started and rapidly titrated to 150 mg twice daily. After 1 month, she was calm, cooperative, and compliant with daily activities, with a significant decrease in OCD-like symptoms. Her dystonia and gait returned to the level at which she had started the haloperidol, but were still impaired.
Case 4
Mr. D was a 42-year-old man with HD and bipolar disorder who was admitted to a long-term facility with worsening dementia and agitation. He had a history of violent behavior and incarceration, and his family had restraining orders against him because of his aggressive behavior. On transfer to the nursing home, he was on haloperidol 1 mg daily, fluoxetine 20 mg daily, and benztropine 0.5 mg daily. Agitated and aggressive, he wandered, ate, and drank compulsively. A lithium trial had little therapeutic effect. Because of problems with gait and dystonic posture, haloperidol was replaced with quetiapine. His motor symptoms did not change; however, he became much calmer and more cooperative, interactive, and amenable to redirection within 2 months on 150 mg daily.
Case 5
Ms. E was a 38-year-old woman with HD and depressive disorder who was admitted to a long-term care facility with worsening dementia and mood lability. She had a history of agitation, depression, and suicide attempts. During her admission, she was on nortriptyline 75 mg daily and haloperidol 1 mg twice daily. After a long period of stability on this regimen, she became increasingly dysphoric, irritable, and demanding, and began to wander in the hallways and disrobe. Paroxetine (up to 60 mg daily) had little effect. Her attempted suicide by hanging prompted a psychiatric hospitalization, during which mirtazapine was given and haloperidol increased. On return to our facility, she was no longer suicidal but remained dysphoric and agitated and had truncal dystonia. Haloperidol was replaced with quetiapine, titrated to 225 mg daily. She became cooperative, pleasant, and interactive within 1 month of starting quetiapine.
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Discussion
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Unfortunately common and troublesome symptoms in patients with HD—psychosis and agitation—respond well to neuroleptic therapy. However, treatment with conventional dopamine-blocking agents (especially those with high potency) can affect voluntary movements, which adversely affects quality of life even more than choreiform movements, and some patients do not respond to the conventional neuroleptics. At our clinic, we preferentially use atypical neuroleptic agents because of their reduced tendency to cause EPS.
In the five patients we presented here, quetiapine successfully ameliorated psychotic symptoms (e.g., paranoid delusions), agitation, irritability, and insomnia. In our second case, switching from a high-potency neuroleptic to an atypical neuroleptic helped with motor symptoms and, despite a brief decompensation, the behavioral problems were improved with the increase of the atypical neuroleptic, as well. We start the quetiapine at 25 mg–50 mg qd and slowly titrate it upward (25 mg–50 mg per week) until it takes effect, and use it as needed to control breakthrough agitation. Our experience suggests that quetiapine is well tolerated in HD patients and effectively treats behavioral problems without worsening the underlying motor disease. Controlled, long-term studies of this and other atypical neuroleptics in the treatment of behavioral disturbances in patients with HD are warranted.
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ACKNOWLEDGMENTS
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The authors thank Dr. John Querques for his help in editing this article.
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REFERENCES
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ABSTRACT
INTRODUCTION
