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Year : 2018  |  Volume : 66  |  Issue : 7  |  Page : 150--152

Risperidone induced rabbit syndrome

Preethi Rebello, Pavithra P Rao, Priya Nayak, Joylin Jovita Mascarenhas, P John Mathai 
 Department of Psychiatry, Father Muller Medical College, Mangalore, Karnataka, India

Correspondence Address:
Dr. P John Mathai
Department of Psychiatry, Father Muller Medical College Mangalore - 575 002, Karnataka

How to cite this article:
Rebello P, Rao PP, Nayak P, Mascarenhas JJ, Mathai P J. Risperidone induced rabbit syndrome.Neurol India 2018;66:150-152

How to cite this URL:
Rebello P, Rao PP, Nayak P, Mascarenhas JJ, Mathai P J. Risperidone induced rabbit syndrome. Neurol India [serial online] 2018 [cited 2021 Jun 13 ];66:150-152
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Rabbit syndrome is a rare form of extra-pyramidal adverse effect of antipsychotic medicines in which perioral tremors occur at a rate of 4-5 Hz. Rabbit syndrome is characterized by involuntary, fine, rhythmic motions of the mouth along a vertical plane, without involvement of the tongue. By and large, it occurs after years of pharmacotherapy, and is more frequent with high-potency first generation drugs like haloperidol, fluphenazine and pimozide.[1],[2],[3],[4] Rare incidences of rabbit syndrome induced by second generation antipsychotic medicines like risperidone, olanzapine, amisulpiride, aripiprazole and clozapine are reported.[3] The reported prevalence of rabbit syndrome ranges from 2.3% to 4.4% in patients treated with first generation antipsychotic medicines. Although there have been isolated reports of rabbit syndrome in patients treated with second generation antipsychotic medicines, to the best of our knowledge, no prevalence study has been published to date on the relationship between rabbit syndrome and newer antipsychotic medicines. Patients with rabbit syndrome are often misdiagnosed as having tardive dyskinesia (TD). The aim of this report is to create awareness of the rare occurrence of rabbit syndrome in patients on the long-term use of newer antipsychotics that include risperidone, aripiprazole and clozapine.

A 47-year old lady with bipolar affective disorder-mania was hospitalized for a period of seven weeks and was discharged with advice to continue divalproate 1000mg and risperidone 8 mg (a serotonin dopamine antagonist). She had been on the same medicines for some years but with poor adherence to medicines and on an irregular follow up. Her episodes had complete remissions with frequent recurrences. On follow up after two weeks in the outpatient department, it was observed that she had minimal perioral abnormal involuntary rhythmic movements. There were no other clinically evident extra-pyramidal features. Risperidone was tapered off and aripiprazole (a dopamine partial agonist)[5] was added to replace risperidone. Divalproate was continued and trihexyphenidyl (2mg) was initiated with the clinical possibility of drug-induced extra-pyramidal syndrome (EPS) developing. At follow up after a week, worsening of the perioral abnormal movements were observed and a clinical possibility of rabbit syndrome was considered, although she was not on first generation antipsychotic drugs. A detailed clinical examination revealed that she had abnormal, involuntary, rhythmic, vertical, perioral movements involving the lips, the frequency of which was about 4-5 HZ, with close resemblance to the chewing movements of the rabbit. The movements were not uniform and there were variations in their frequency and amplitude. The movements could not be suppressed voluntarily. Distraction did not reduce the movements, and anxiety and anger did not worsen the same. The perioral movements were reduced during early sleep and completely disappeared during a good sleep. There were no other rhythmic or choreo-athetoid abnormal movements of the face or extremities or of other parts of the body. The tongue was involved. Fine tremors were observed on the tongue on opening the mouth. There were no protruding or other choreo-athetoid movements of the tongue. There was no rigidity or bradykinesia. Neurology opinion was sought and the neurologist's opinion was in favour of drug induced perioral tremor, possibly tardive dyskinesia (TD), because of the involvement of the tongue and the late onset of the rhythmic movements. The patient was advised by the neurologist to stop trihexyphenidyl. She was admitted in the psychiatry ward. During the first week of hospitalization, since the movements did not improve, the patient was given promethazine tablets 25 mg twice daily. Minimal improvement was observed in two days and hence trihexyphenidyl (4mg) was reintroduced. There was marked improvement in the tremors within two days and the perioral tremors disappeared completely in a week's time. Divalproate was continued as the mood stabilizer, and quetiapine (a multi- acting receptor targeted antipsychotic) replaced aripirazole. The patient was discharged with complete remission of her perioral movements and mood symptoms.

This report illustrates the difficulty in diagnosing rabbit syndrome in a patient with perioral movement disorder and in differentiating it from TD involving buccolinguomasticatory (BLM) muscles.[1],[2],[4],[6],[7] The distinction is of great importance because the treatment options for the two disorders are quite different. Rabbit syndrome is an eminently treatable disorder, and with anticholinergic drugs, the perioral tremor usually disappears in a few days. On the other hand, anticholinergic drugs will worsen the BLM TD.

The clinical characteristics of the abnormal movements helped us differentiate rabbit syndrome from TD and essential tremor. Absence of choreo-athetoid dyskinesia in other parts of the face, extremities and trunk, absence of such movements of the tongue and a quick response to anticholinergics ruled out the possibility of TD in this patient. Unlike TD, the movements could not be suppressed voluntarily to any extent. There was no reduction in the movement on distraction and neither was there exacerbation during anxiety or other emotional distress. However, the involvement of the tongue which is not expected in rabbit syndrome produced problems in diagnosing it at the onset and the ailment was misdiagnosed as TD. It is reported that patients with rabbit syndrome are often misdiagnosed as having TD.

Our patient was using divalproate, and hence, the possibility of an essential tremor was also considered. The presence of the tremor confined exclusively to the perioral region with absence of the tremor of the extremities and other parts of body was not in favour of essential tremor. Besides, movements in essential tremor are finer and more rapid than that of rabbit syndrome. The fine tremor of the tongue was more characteristic of the essential tremor than that of rabbit syndrome. Perioral tremor as a part of the extrapyramidal adverse effect of risperidone was ruled out because of the conspicuous absence of rigidity, bradykinesia and parkinsonian tremor anywhere in the body other than the oral region.

Like EPS, TD and neuroleptic malignant syndrome (NMS), rabbit syndrome also may be caused by the second generation antipsychotic medicines. There are reports of rabbit syndrome induced by risperidone, olanzapine, aripirazole, amisulpiride, levosulpiride and clozapine and on discontinuation of paliperidone and ziprasidone.[3],[5],[6],[7],[8],[9],[10] Antipsychotic medicines ( first generation antipsychotics, a larger dose, and a higher potency), brain damage, older age, female gender, a family history of Parkinson's Disease, mood disorders and Asian ethnicity are few of the risk factors reported that may be responsible for the development of rabbit syndrome. The etiology and pathophysiology of rabbit syndrome are uncertain.[4] It usually occurs while the patient is on first generation antipsychotic medicines. It is reported to occur on sudden discontinuation of antipsychotic medication. It is also reported to occur rarely without the patient receiving any antipsychotic medicines. It is usually of late onset but can also occur in the early phase of treatment. The perioral tremor of rabbit syndrome disappears with anticholinergic drugs and is made worse with physostigmine. Thus, rabbit syndrome has certain mechanisms that work in favour as well as against the diagnosis of both EPS and TD. It possibly could be a rare variant of one of them and is usually associated with a very good recovery.[4]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.


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