Article as Full-Text Content   Catalog Help
Letter Pharmacopsychiatry 2003;  41-43
DOI: 10.1055/s-2003-38093

Received: 16.10.2001
Revised: 26.2.2002
Accepted: 8.5.2002

Fluoxetine-induced Exacerbation of Chorea in Huntington’s Disease?

A Case Report

S. Chari1, S. H. Quraishi1, A. K. Jainer1
1 The Caludon Centre, Clifford Bridge Road, Coventry CV2 2TE, UK


Huntington’s chorea continues to pose challenges in the management of both psychiatric and neurological symptoms. The disorder, which was first described in 1872, is widely acknowledged to be due to a gene mutation that lies in the short arm of Chromosome 4. The pathology mainly affects the basal ganglia, in particular the caudate nucleus and the putamen. Wanker [10] recently wrote about the accumulation of highly insoluble intracellular protein aggregates in neuronal inclusions as a hallmark of Huntington’s disease (HD), Parkinson’s disease (PD), and several other late-onset neurodegenerative disorders. The aggregates formed generally have a fibrillar morphology, consist of individual beta-strands, and are resistant to proteolytic degradation. Myrianthopolous estimated the prevalence to be in the range of 4 to 7 per 100,000 population in the UK [6]. The inheritance is autosomal dominant, with 50 % of the offspring being affected and virtually all manifesting the disease.

Heathfield [3] concluded that the symptoms were almost equally divided between neurological and psychiatric symptoms. The neurological symptoms of chorea - hemichorea, dysarthria, ataxia, disturbance in fine motor task completion, and a conspicuous slowness of movement - are well recognized. The psychiatric symptoms of cognitive impairment giving rise to a subcortical dementia, pervasive apathy, self-neglect, marked depression, persecutory delusions, and suicide are also well known [5].

The Case

We write about the case of a 46-year-old Caucasian gentleman, with a diagnosis of Huntington’s disease confirmed in 1995 by the West Midlands Regional Genetic Services in the UK. His mother had died at the age of 47 from the same illness. He was referred to the psychiatric services by a neurologist, who had been seeing him since 1995. The reason for the referral was for the management of excessive hand washing, which had reached a disabling degree and met the criteria for an ICD-10 [11] diagnosis of an obsessive-compulsive disorder (OCD). Unfortunately, the degree of OCD was not quantified using standardized scales. Prior to this referral, he had never been in contact with psychiatric services and had not suffered from symptoms of OCD.

The neurologist treated the patient’s chorea with tetrabenazine, which depletes dopamine at the nerve endings, at a dose of 25 mg three times daily orally, but this appeared to cause a deterioration in his symptoms. He was then started on haloperidol at a dose of 5 mg twice daily orally, which seemed to reduce his symptoms of chorea, but, unfortunately, no scales were used to quantify the difference. Following psychiatric assessment in November 1999, he was started on 20 mg of fluoxetine orally, a selective serotonin reuptake inhibitor (SSRI) to control his OCD symptoms. He was considered for cognitive behavioral therapy but was felt to be an unsuitable candidate because of the severity of his chorea.

Within a couple of days, he noticed a marked exacerbation of his chorea, and this continued over the two weeks that he was taking fluoxetine. This exacerbation of the chorea was corroborated by the patient, his wife, and the neurologist.

On review at the psychiatric clinic, the fluoxetine was stopped and he was switched to clomipramine, a tricyclic antidepressant that is known to be effective in the treatment of OCD, but he continued on haloperidol at a dose of 5 mg twice daily orally. The clomipramine was initiated at a dose of 25 mg per day and titrated upwards to achieve a dose of 100 mg per day.

In July 2000, he was seen by a neuropsychiatrist with a special interest in movement disorders, who felt that risperidone 1 mg four times per day instead of the haloperidol would be more suitable. This did not change his physical situation significantly, but his depression became more pronounced, with a pervasive low mood, tearfulness, low energy, and no motivation. His sleep became more erratic, with early morning wakening and a poor appetite. However, the depression and the OCD were brought under control by increasing the clomipramine to 200 mg per day.

Though the management of OCD is often difficult and has periodic relapses, we are pleased to report that to date there has been no relapse of his psychiatric symptoms, and he continues to be seen on a monthly basis. Unfortunately, his gait and chorea are getting worse and he and his family are aware of the prognosis of his illness.


There are two interesting learning points from this case. First, that OCD is not a common feature in Huntington’s chorea. To the best of our knowledge, there has been only one case report about the presence of OCD in Huntington’s disease [8].

However, given that both OCD and Huntington’s chorea are believed to affect the basal ganglia, the co-morbidity is not altogether unexpected but is unusual in that it is not a more frequent symptom. Recent neuroimaging studies [7] have suggested that OCD also involves abnormal functioning of specific frontal-subcortical circuits, and this may be a possible explanation for the above.

The initiation of fluoxetine was temporally linked to the exacerbation of the chorea, and this quickly settled when it was replaced with clomipramine. Biochemical studies have identified reduced levels of GABA, particularly in the basal ganglia [2], and a cholinergic neurone deficiency in the striatum. However, the dopaminergic system appears to be spared, and Spokes hypothesized [9] that the intact nigrostriatal dopaminergic pathway releases dopamine onto a depleted number of striatal neurones, leading to over-stimulation of the pathway that manifests as chorea.

Normally, there is a delicate balance between serotonin and dopamine in the major dopamine pathways, and serotonin inhibits dopamine release. In this case, it could be postulated that the fluoxetine upset this balance and caused an accentuation of the chorea. The differential effect of these two drugs could be because of the individual drug action on particular serotonin pathways, particularly in the basal ganglia. Bharucha and Sethi [1] have written about the development of complex movement disorders including rhythmic palatal movements, myoclonus, and chorea after two years of therapy on fluoxetine. Upon withdrawal of fluoxetine, the movements abated within a week and did not recur.

Many SSRIs have been associated with extrapyramidal side effects [4], and it could be that the changes in basal ganglia occurring in Huntington’s chorea make the occurrence of the extrapyramidal symptoms more likely.

Another possible explanation for the exacerbation of the chorea is the widely acknowledged phenomenon that many SSRIs, on initiation, cause a temporary increase in anxiety and agitation. This may have manifested as increased chorea.


We highlight two learning points in this case report. The first point is the occurrence of OCD as a psychiatric manifestation of Huntington’s chorea. Second is the possibility of an exacerbation of chorea or other movement disorders when treated with SSRIs in general and fluoxetine in particular.

Given that fluoxetine is now generically available at a low cost, there will be greater prescribing and consequently a greater potential for such side effects, which may not be easily recognized or managed.


1 Bharucha KJ, Sethi KD. Complex movements disorders induced by fluoxetine. Movement Disorders 1996; 11 (3): 324-326
This article in:

2 Bird ED, Iverson LL. Huntington’s chorea - postmortem measurement of glutamic acid decarboxylase, choline acetyltransferase and dopamine in basal ganglia. Brain 1974; 97: 457-472
This article in:

3 Heathfield KWG. Huntington’s chorea. Brain 1967; 90: 203-232
This article in:

4 Jimenez-Jimenez FJ, Molina JA. Extrapyramidal symptoms associated with selective serotonin reuptake inhibitors, epidemiology, mechanisms and management. CNS Drugs 2000; 14 (5): 367-379
This article in:

5 Lishman WA. Organic Psychiatry. Oxford Blackwell Science 1998 , p. 469-470

6 Myrianthopolous NC. Huntington’s chorea. J Med Gen 1966; 3: 298-314
This article in:

7 Saxena S Brody AL, Schwart JM, Baxter LR. Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder. B J Psych 1998; 173 (suppl 35): 26-37
This article in:

8 Scicutella A. Late-life obsessive-compulsive disorder and Huntington’s disease. J Neuropsy Clin Neurosci 2000; 12: 228-289
This article in:

9 Spokes EGS. Neurochemical alterations in Huntington’s chorea: a study of post-mortem brain tissue. Brain 1980; 103: 179-210
This article in:

10 Wanker EE. Protein aggregation in Huntington’s and Parkinson’s disease: implications for therapy. Mol Med Today 2000; 6 (10): 387-391
This article in:

11 World Health Organisation (eds). The ICD - 10 classification of mental and behavioural disorders. Geneva WHO 1995 

Dr. Suresh Chari
Specialist Registrar
The Caludon Centre
Clifford Bridge Road
Coventry CV2 2TE
Phone: UK +24-7660 2020 x 7132
Fax: UK +24-7653 8920