Abstract
Aripiprazole is considered to be an example of the next generation of antipsychotics, due to its unique mechanism of action as a dopamine-system stabilizer [1]. Data published so far has revealed no significant difference between aripiprazole and placebo in the mean change from baseline on extrapyramidal rating scales [2]. Rabbit syndrome is a distinct antipsychotic-induced extrapyramidal syndrome and gains its name from a resemblance to the chewing and puckering motions of the rabbit [3], [4].
A manual and computer search did not find any report of rabbit syndrome associated with aripiprazole. We report rabbit syndrome associated with aripiprazole.
Mrs M, a 29-year-old married woman, presented with a one-month history of suspiciousness, withdrawal and muttering to herself. There was no past or family history of psychiatric or neurological illness. Her mental status examination revealed persecutory delusions, second person auditory hallucinations, inappropriate affect and negativism. A diagnosis of schizophreniform disorder was made (DSM-IV criteria) and she was commenced on risperidone 2 mg/day, increased to 6 mg/day over a period of 2 weeks. At week 3 of therapy, she developed extrapyramidal symptoms (EPS) in the form of rigidity, tremor, bradykinesia, and salivation. Hence, trihexiphenidyl 4 mg/day was added and complete resolution of EPS was noticed at day 4. She continued to receive risperidone 6 mg and trihexiphenidyl 4 mg for the next 8 weeks without improvement in her psychiatric symptoms. Therefore, this combination was replaced by aripiprazole 10 mg/day as monotherapy. Although she showed improvement in psychopathology, at 6 weeks of aripiprazole therapy, she exhibited rapid involuntary, fine and rhythmic, vertical movements of the jaw; there were no associated abnormal tongue movements. These movements were rated as moderate in severity on the Abnormal Involuntary Movements Scale. She also had moderate to severe parkinsonism. Her oral movements disappeared within 10 minutes of intravenous administration of promethazine (50 mg); however, there was minimal response in the akinesia and rigidity. Subsequently, the dose of aripiprazole was decreased to 5 mg/day and trihexiphenidyl 4 mg/day was added. At day 5 of this combined therapy, she showed complete recovery from all EPS. Detailed neurological examination and other relevant laboratory investigations including CT of the head were normal. She was maintained on the above drugs with no further appearance of extrapyramidal symptoms.
Aripiprazole is a dopamine receptor partial agonist with a partial agonistic activity at the serotonin 5HT1 A receptor and antagonistic activity at 5HT2 A receptor. It has shown a low potential for EPS in clinical trials. We consider it likely that aripiprazole was the cause of the parkinsonism and the rabbit syndrome in this case.
The possibility of risperidone withdrawal dyskinesia in the form of rabbit syndrome [5] appears unlikely, as the patient was on risperidone for 6 weeks prior to the appearance of rabbit syndrome.
In conclusion, it appears that a non-dopamine receptor antagonist can induce rabbit syndrome. An anticholinergic agent and dose reduction may be the treatment of choice.