Rabbit Syndrome: Definition and Clinical Characteristics
Rabbit syndrome is a rare antipsychotic-induced extrapyramidal side effect characterized by rapid, fine, rhythmic vertical movements of the mouth and lips (approximately 5 Hz frequency) that resemble the chewing motions of a rabbit, with the critical distinguishing feature being the complete absence of tongue involvement. 1
Key Diagnostic Features
- Movement pattern: Vertical-only motion of the mouth/lips at about 5 Hz frequency, with no lateral or rotatory components 1, 2
- Anatomical specificity: Affects only the buccal (mouth) region; tongue remains completely uninvolved, which is the critical distinguishing feature from tardive dyskinesia 1, 3
- Appearance: The involuntary movements closely resemble the chewing and puckering motions of a rabbit 3
Epidemiology and Causative Agents
- Prevalence: Ranges from 2.3% to 4.4% of patients treated with typical antipsychotics 1
- Onset timing: Usually appears after prolonged antipsychotic treatment (months to years), though rare cases occur without antipsychotic exposure 1
- Associated medications:
Critical Diagnostic Pitfall
The most common misdiagnosis is oral tardive dyskinesia. The key differentiating feature is that tardive dyskinesia involves tongue movements (lateral, rotatory, or protrusion), while rabbit syndrome has absolutely no tongue involvement—only vertical lip/mouth movements. 1
Pathophysiology
- Neuroanatomical localization: The syndrome's extreme specificity to the buccal region with stereotyped movements implicates the basal ganglia, particularly the substantia nigra pars reticulata 1
- Mechanism: Likely related to dopamine-serotonin interactions, as evidenced by withdrawal-emergent cases during risperidone dose reduction 4
- Classification: Considered an extrapyramidal side effect based on rapid response to anticholinergic medication 3
Treatment Algorithm
Step 1: Reduce antipsychotic dosage as much as clinically feasible 1
Step 2: If full withdrawal is impossible (most cases), initiate anticholinergic therapy:
- Trihexyphenidyl is the first-line treatment and typically produces rapid symptom control 4, 1
- Anticholinergic drugs are the best-known and most effective treatment 1
Step 3: Do NOT use levodopa or dopamine agonists—rabbit syndrome does not respond to these agents 1
Special Considerations
- Withdrawal-emergent cases: Can occur during dose reduction of atypical antipsychotics, particularly risperidone, suggesting serotonergic system involvement 4
- Atypical antipsychotics: Despite lower overall extrapyramidal side effect profiles, aripiprazole, risperidone, clozapine, and olanzapine can all cause rabbit syndrome, requiring vigilant monitoring 2, 5
- D2 receptor occupancy: Even atypical agents with partial D2 agonism (like aripiprazole) can induce the syndrome, emphasizing the need for caution regardless of the antipsychotic's pharmacological profile 5