Clozapine-Induced Rabbit Syndrome
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Mental Illness 2009; volume 1:e1 Clozapine-induced rabbit highest incidence of extrapyramidal symptoms (EPS). 5 An extensive literature search revealed Correspondence: Cicek Hocaoglu, Associate syndrome: a case report 11 cases of RS related to newer antipsychotic Professor, Rize University, Medical School, studies reported by Dell'Osso et al. 6 Eight of Department of Psychiatry, 53000, Rize, Turkey. Cicek Hocaoglu the 11 reported cases of RS are linked to E-mail: [email protected], Department of Psychiatry, Faculty of risperidone. 6-12 The 3 remaining cases occurred cicekh@ gmail.com Medicine, Rize University, Rize, Turkey with clozapine, olanzapine, and aripiprazole, Key words: schizophrenia, clozapine, rabbit syn - respectively. 13-15 These atypical antipsychotics drome. are characterized by a relatively low incidence of EPS. It is interesting that, in the case Received for publication: 28 June 2009. Abstract induced by clozapine, TD preceded RS which Revision received: 2 October 2009. developed after treatment for approximately Accepted for publication: 2 October 2009. Rabbit syndrome (RS) is an antipsychotic- two years with chlorpromazine, haloperidol, This work is licensed under a Creative Commons induced rhythmic motion of the mouth/lips and fluphenazine decanoate, either in Attribution 3.0 License (by-nc 3.0). resembling the chewing movements of a rab - monotherapy or in combination. 6 In addition, bit. The movement consists of a vertical-only there are 3 new case reports concerning EPS, ©Copyright C. Hocaoglu, 2009 motion, at about 5 Hz, with no involvement of which include RS associated with aripiprazole Licensee PAGEPress, Italy the tongue. Long-term exposure to typical and olanzapine. 16-18 Mental Illness 2009; 1:e1 antipsychotics has clearly been associated It has been postulated that the underlying doi:10.4081/mi.2009.e1 with RS, but little is known of the risk of RS mechanism of RS is supersensitivity of due to exposure to newer atypical antipsy - dopamine receptors, possibly due to an under - chotics. There have been isolated reports of RS lying predisposition. 16 Treatment of RS is scribed with haloperidol (20 mg) irregularly in patients treated with the atypical agents empirical, reflecting poor understanding of and then she was prescribed with anti-psy - risperidone, aripiprazole, olanzapine, and neuropathology. The first step is to reduce the chotics such as fluphenazine decanoate (25 clozapine. We present the case history of a 44- dose of antipsychotic treatment as much as mg), trifluoperazine (5 mg), thioridazine (100 year old female patient treated for paranoid possible. The next stage of treatment involves mg), zuclopentixol (200 mg). It was also said schizophrenia for 22 years and RS during her specific drugs aimed at controlling the syn - that in the last five years of her treatment she last 10-month clozapine treatment. Back- drome. Anticholinergic drugs are the best was prescribed with olanzapine 20 mg/day and ground information from the literature is also known treatment. RS does not respond to treat - risperidone 6 mg/day irregularly. Some side discussed. ment with levodopa or dopamine agonists. 3 effects, such as a frequent sensation of slowing The most striking aspect of this syndrome is down, limited movements, tremor in her hands its specificity. RS only affects the buccal and dryness in her mouth, were observed dur - region, and within this area it involves a high - ing the period of medication. The family point - Introduction ly stereotyped involuntary movement. This ed out that there had been some improvement immediately focuses attention on the basal in her condition while she was taking her med - Rabbit syndrome (RS) is a rare movement ganglia, in particular the substantia nigra pars ications, but their side effects compromised disorder generally associated with prolonged reticulata, which is also implicated in oral continuity of treatment. Her symptoms wors - use of antipsychotics and characterized by dyskinesia. 3 ened and her family brought her to the hospital. involuntary, rhythmic, fast, and fine move - On presentation she had not taken prescribed ments of the oral and masticatory muscles medication for seven months. along the vertical axis of the mouth. 1 It takes MO was the youngest of 3 children and had its name from an unusual resemblance to the Case Report an older brother and sister. Her mother was a chewing motions of rabbits. The pattern of 68-year old housewife who had finished ele - movement differs from tardive dyskinesia MO was a 44-year old single woman born in mentary school. Her father had died in an acci - (TD), another form of oral dyskinesia, in Artvin in Turkey. She was unemployed and had dent 20 years earlier. There was no history of which the tongue is involved in making slower dropped out of university in her sophomore any neurological or psychiatric disease in the and less regular movements. 2 Usually, the year. She was brought into our hospital by her family. She had been successful at school and involuntary movements associated with RS family against her will. She was complaining had gone to Ankara to study at the university appear after a long period (in most cases of paranoia and introversion. In addition, she after passing the entrance exam. In the first months or years) of antipsychotic treatment. 3 refused to speak, eat or leave her house. She year, she had stayed in a dormitory with her Gender and age are also thought to be related also rejected other people’s company and pre - friends but in the second year she began to live to the development of RS. This syndrome is ferred to stay on her own. She could not sleep. alone in a flat. She had to drop out of universi - found predominantly in middle-aged and elder - According to her family, her first complaint ty in the second year because of her illness. ly patient populations; women are also thought had started at the age of 22 before she went to She had not had any medical problems before to be at higher risk of developing RS than university in Ankara. Based on information her illness. She had been smoking one packet men. 4 The reported prevalence of RS ranges from her family, we learnt that she had begun of cigarettes every three days. However, this from 2.3-4.4% of patients treated with typical to skip classes and this had had a negative amount had increased over the previous few antipsychotics. 3 To the best of our knowledge, impact on her academic achievement. Also her months. Six months before presentation she no prevalence study has been published to date family said that she was hearing strange nois - had begun to suffer from eating disorders and on the relationship between RS and atypical es. Since then she had been treated in differ - insonnia, although she had had no previous antipsychotics. Of particular interest and ent hospitals and cities, being given various history of either. She refused meals prepared importance is the risk of RS with exposure to medications based on the diagnosis of para - by her mother, believing them to be poisoned. newer atypical antipsychotics. Risperidone is noid schizophrenia. It was reported that in the According to her family, the patient had been considered the atypical antipsychotic with the first 15 years of her treatment she was pre extrovert, more talkative, and generally happi - [Mental Illness 2009; 1:e1] [page 1] Case Report er and livelier before her illness. She had sub - (AIMS) score dropped from 14 to 8. The most males. Moreover, different antipsychotic drugs sequently become introverted and never want - prominent, albeit controversial, treatment were used before clozapine and the fact that ed to leave the house. She was still living with agents for RS are benzhexol and biperiden. We EPS symptoms emerged is remarkable. This her mother and her unmarried sister, six years were anxious to avoid aggravation or TD by the shows the importance of individual factors in older than herself. addition of anticholinergic agents. RS. For this reason, it is important to diagnose the side effects emerging during antipsychotic Physical examination and drug treatment to determine which individuals laboratory findings are at risk of being exposed to EPS and to pre - Discussion vent possible negative results. Furthermore, Vital findings, neurological and other sys - increased awareness in medical practice that tem examinations were all normal. atypical antipsychotics cause RS, albeit rarely, Laboratory findings, hemogram, EFG, and Increased knowledge about neurobiology will be beneficial in both patient compliance brain magnetic resonance image (MRI) were has improved our understanding of the patho - physiology of schizophrenia. These improve - with treatment and in providing data for more also all normal. ments have led to the development of new gen - comprehensive models to explain RS progress. At her first psychiatric appointment, the eration antipsychotics with fewer side effects female patient, who looked older than her and more therapeutic effectiveness. Clozapine years, looked well groomed and behaved with is considered an atypical antipsychotic drug. respect. She kept looking around, didn’t speak Atypical antipsychotics differ from typical References spontaneously, and replied hesitantly only antipsychotics in their effectiveness in schizo - when asked questions. During the interview phrenia and their profile of side effects. 1. Catena M, Fagiolini A, Consoli G, et al. The she was agitated, her attention and concentra - Clozapine may reduce the signs and symptoms rabbit syndrome: state of the art. Curr Clin tion were poor, and she did not always seem to of schizophrenia in a large proportion of treat - Pharmacol 2007;2:212-6. understand what was being asked of her. She ment-resistant schizophrenic patients who do 2. Deshmukh DK, Joshi VS, Agarwal MR. showed no emotional response to the conver - not respond to typical antipsychotics. Rabbit syndrome - a rare complication of sation and admitted to hearing voices that dis - Moreover, the drug is less likely to cause tar - long-term neuroleptic medication.