Rabbit syndrome

Overview

Rabbit syndrome is a rare form of extrapyramidal side effect caused by long-term use of antipsychotic medications, particularly first-generation (typical) antipsychotics. It is characterized by fine, rhythmic, and rapid movements of the perioral muscles (around the mouth), which resemble the chewing or twitching motions of a rabbit. Unlike tardive dyskinesia, which involves broader facial and tongue movements, rabbit syndrome is confined to the mouth and does not involve the tongue.

This syndrome typically appears after prolonged exposure to dopamine-blocking agents and may be reversible if recognized early. Although relatively uncommon, it serves as an important indicator of drug-induced movement disorders and can significantly affect the patient's quality of life.

Causes

The primary cause of rabbit syndrome is the long-term use of dopamine antagonist medications, especially typical antipsychotics such as:

• Haloperidol

• Fluphenazine

• Chlorpromazine

• Perphenazine

The syndrome arises due to dopamine receptor blockade in the basal ganglia, particularly the nigrostriatal pathway, which plays a central role in coordinating voluntary motor movements. The chronic suppression of dopamine in this region may lead to an imbalance in the neurotransmitter systems involved in motor control, resulting in the characteristic perioral movements.

In some rare cases, even second-generation (atypical) antipsychotics have been implicated, especially at higher doses or in sensitive individuals. Additional risk factors include older age, female gender, and a history of extrapyramidal symptoms.

Symptoms

The hallmark symptom of rabbit syndrome is:

• Fine, rapid, rhythmic movements of the mouth and lips resembling a rabbit’s chewing motion

Other associated features may include:

• No involvement of the tongue (unlike tardive dyskinesia)

• Preserved voluntary control over facial muscles

• Absence of other involuntary movements in limbs or trunk

• Increased symptoms during stress or anxiety

These symptoms can be distressing and socially embarrassing, often leading to social withdrawal or emotional distress in affected individuals.

Diagnosis

Diagnosis of rabbit syndrome is clinical and based on careful observation of the patient’s motor activity, especially the perioral region. Key diagnostic steps include:

• Detailed history of antipsychotic use, especially duration and dosage

• Neurological examination to assess involuntary motor movements

• Exclusion of other movement disorders such as tardive dyskinesia, Parkinsonism, or orofacial dystonia

There are no specific laboratory or imaging tests for rabbit syndrome, but neuroimaging may be performed to rule out structural causes of abnormal movements if clinically indicated.

Treatment

Treatment of rabbit syndrome focuses on adjusting or discontinuing the offending medication. Common therapeutic strategies include:

• Discontinuation or dose reduction of the antipsychotic drug, if clinically feasible

• Switching to a second-generation antipsychotic with lower risk of extrapyramidal symptoms (e.g., quetiapine, clozapine)

• Anticholinergic medications such as benztropine or trihexyphenidyl, which often produce rapid improvement in symptoms

• Amantadine may be considered in some cases as an alternative

It is crucial to balance the management of psychiatric symptoms with the need to reduce motor side effects. Collaboration between psychiatry and neurology is often beneficial in these cases.

Prognosis

The prognosis for rabbit syndrome is generally favorable, especially when identified early and managed appropriately. Many patients experience significant improvement or complete resolution of symptoms with treatment modifications. However, in some cases, especially with delayed diagnosis, symptoms may persist or become less responsive to intervention.

Unlike tardive dyskinesia, rabbit syndrome is more likely to respond to anticholinergic therapy and is often reversible. Ongoing monitoring and medication reviews are essential to prevent recurrence or progression of extrapyramidal symptoms.