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A Report of Rabbit Syndrome Who Benefited from Sigma 1 Agonist Fluvoxamine

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A Report of Rabbit Syndrome Who Benefited from Sigma 1 Agonist Fluvoxamine Case Report https://doi.org/10.9758/cpn.2019.17.1.134 pISSN 1738-1088 / eISSN 2093-4327 Clinical Psychopharmacology and Neuroscience 2019;17(1):134-138 Copyrightⓒ 2019, Korean College of Neuropsychopharmacology A Report of Rabbit Syndrome Who Benefited from Sigma 1 Agonist Fluvoxamine Yakup Albayrak, Murat Beyazyüz, Özlem Abbak, Ece Altındağ Department of Psychiatry, Faculty of Medicine, Namık Kemal University, Tekirdag, Turkey Rabbit Syndrome is an uncommon side effect of antipsychotic treatment. Although it is usually associated with typical antipsychotics, it can also be related to atypical antipsychotics. Anticholinergics are the most accepted treatment ap- proach in treating Rabbit Syndrome. Fluvoxamine is a member of selective serotonin reuptake inhibitors and it is a potent agonist of sigma 1 receptors. In this article, we report a Rabbit Syndrome case who has benefited from fluvox- amine, in terms of both depressive disorder and Rabbit Syndrome; and present the data on the effects of sigma 1 agonist fluvoxamine on numerous movement disorders. KEY WORDS: Rabbit syndrome; Sigma receptors; Side effect; Fluvoxamine. INTRODUCTION Although all SSRIs share the same mechanism of action by means of the serotonergic system, their effects on sigma 1 Fluvoxamine is a selective serotonin reuptake inhibitor receptors vary. Among these drugs, fluvoxamine exerts (SSRI) which is used for the treatment of depressive dis- the most potent agonistic activity on sigma 1 receptors.3,11) order and obsessive compulsive disorder.1,2) Besides its ef- There have been experimental studies which demon- fect on the serotonergic system, it was well established strated the effects of fluvoxamine as a potent sigma 1 re- that fluvoxamine is a potent sigma 1 chaperone receptor ceptor agonist. Furthermore, there have been clinical agonist.3) The data on the effects of sigma 1 agonism on studies and case reports which reported the beneficial ef- neuropsychiatric diseases is limited. Sigma receptor ago- fects of fluvoxamine, by means of sigma 1 receptor ago- nism has various effects on the central nervous system, as nistic activity, on numerous neuropsychiatric diseases.10) well as on other systems of body via Ca signaling, protein Rabbit syndrome is a drug induced movement disorder kinase translocation or activation, ion channel firing, neu- that is particularly associated with antipsychotics.12) It is rotransmitter release, cellular differentiation, neuronal relatively uncommon and is characterized by rhythmic survival, and synaptogenesis.4-9) Several therapeutic drugs, movements of perioral muscles, which seems as the ap- which have been used on humans, and some neuro- pearance of a chewing rabbit. It has been reported to steroids such as dehydroepiandrosterone have high to commonly be associated with typical antipsychotics13); moderate sigma-1 receptor affinity. Cumulative data sug- however, it can also be associated with atypical antipsy- gest benefits of sigma 1 agonism on neuropsychiatric dis- chotics.12,14) Here, we report a case, who developed eases, however there still has not been any exact ex- Rabbit syndrome after long acting risperidone treatment, planation which can highlight the action of mechanism.10) and benefited from fluvoxamine in terms of both depres- sive symptoms and symptoms of Rabbit syndrome. Received: March 17, 2017 / Revised: June 17, 2017 Accepted: July 19, 2017 Address for correspondence: Yakup Albayrak, MD CASE Department of Psychiatry, Faculty of Medicine, Namik Kemal Universitesi, Tıp Fakültesi, Kampus Cad. No:1 Tekirdag, Turkey A 62-year-old man admitted to outpatient clinic with Tel: +90-5056355434, Fax: +90-2822509928 E-mail: [email protected] symptoms of depressive mood, anhedonia, insomnia, de- ORCID: https://orcid.org/0000-0002-1926-1695 This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 134 Rabbit Syndrome Benefited from Agonist Fluvoxamine 135 creased appetite, difficulty in concentration, ideas of Routine laboratory examination, brain magnetic reso- hopelessness, psychomotor agitation, and abnormal nance imaging, and other neurological assessments were movements of the lips. In his history, his complaints be- unremarkable. The patient was diagnosed as major de- gan four months ago as; being followed by strangers, pressive disorder and medication induced movement dis- hearing voices that commented and humiliated him, be- order (Rabbit syndrome) according to DSM-5. ing unable to leave his home, a decrease of self hygiene, Fluvoxamine 100 mg/day was prescribed as his current increase in irritability, and having some homicidal at- treatment; whereas, biperiden and diazepam treatments tempts to family members. The patient had been taken to were stopped. The patient was recommended to be fol- a psychiatrist without his will and he had been assured to lowed up bimonthly in our outpatient clinic. In his first as- be examined by a psychiatrist. sessment, there was a significant improvement in symp- At initial assessment, the patient was assessed with rou- toms of Rabbit syndrome and a moderate amelioration in tine laboratory and toxicology examinations, brain mag- depressive symptoms. The dose of fluvoxamine was in- netic resonance imaging, and electroencephalogram. creased to 200 mg/ day. After the second assessment, the Both physical and laboratory examination had been re- patient was asymptomatic in terms of Rabbit syndrome, sulted unremarkable, thus organic etiology had been and there was significant improvement in depressive excluded. Moreover, he had scored a 26 in the mini men- symptoms. During the follow-up outpatient visits, the pa- tal status examination. The patient had been diagnosed tient was noted to be asymptomatic in terms of both with “brief psychotic disorder” according to Diagnostic Rabbit syndrome and depressive disorder. and Statistical Manual of Mental Disorders, fifth edition (DSM-5)15) by a psychiatrist working in another center. DISCUSSION After his psychiatric and physical assessment, the patient had been given a treatment of olanzapine 10 mg/day. In the present case, we reported the beneficial effect of During his first outpatient control on the fifteenth day of sigma 1 agonist fluvoxamine on symptoms of Rabbit syn- treatment, it had been noticed that the patient was non ad- drome and depressive disorder. The etiology of Rabbit herent to oral treatment and his symptoms persisted. The syndrome is unclear, and it is commonly confused with patient had been given 25 mg of long acting risperidone and misdiagnosed as tardive dyskinesia.12) Due to the fact treatment bimonthly, due to lack of adherence to oral that Rabbit syndrome is commonly seen after anti- treatment. After the fourth injection of risperidone (at the psychotic treatment, the etiology has been considered to second month), the psychotic symptoms were reported to be associated with the dopaminergic system.16) Rabbit be remitted; however, abnormal movements of lips syndrome is generally known to occur due to long-term developed. Because of the remission of his initial symp- use of typical antipsychotics with a range between 1.5% toms and development of abnormal movements, the treat- and 4.4%.17) Quetiapine, clozapine, olanzapine, aripipra- ment of 25 mg of long acting risperidone had been zole, paliperidone, amisulpride, and most commonly ris- stopped. The abnormal movements of the lips were con- peridone have been reported to be associated with the de- sulted with the neurology department, and the patient’s velopment of Rabbit syndrome.14) In terms of treatment, neurological examination had been reported to be the most acceptable approach is using anticholinergic unremarkable. The patient had been treated with biper- drugs, such as benzatropine, biperiden, trihexyphenidyl.12) iden 6 mg/day for 3 weeks, and diazepam 5 mg/day had In some case reports, haloperidol, olanzapine, sulpiride, been added to his treatment for 5 weeks due to lack of re- and chlorpromazine were reported to be effective in the sponse to biperiden treatment in terms of abnormal move- treatment of Rabbit syndrome.18) However, the present ments of his lips. case is the first to demonstrate the beneficial effect of sig- After these interventions, the patient admitted to our ma 1 agonist fluvoxamine on Rabbit syndrome. outpatient clinic at the fourth month of his treatment. In Sigma 1 receptors include 223 amino acids and as not- his psychiatric and physical examination, abnormal ed in the introduction section, they have been associated movements of lips in a vertical axis, being fine, rapid, and with many cellular functions, such as cellular redox, cel- rhythmic, were noted additional to depressive symptoms. lular survival, neurotransmitters release etc.4-9) It has been 136 Y. Albayrak, et al. demonstrated that sigma 1 receptors act as a chaperone, might mediate beneficial effects for the movement dis- and have the ability to fix and stabilize endoplasmic retic- orders mentioned above. ulum proteins. Both clinical and experimental studies re- Anticholinergic agents such as, benzatropine, biper- ported various effects of sigma 1 receptors on various sys- iden, trihexyphenidyl are accepted to be the most effec- tems throughout the body, such as the cardiovascular sys- tive agents for the treatment of Rabbit syndrome12);
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