Atypical extrapyramidal manifestation of a typical antipsychotic with serotonergic antidepressant

Abstract

Introduction

Typical antipsychotics are known to produce extrapyramidal side effects such as drug induced parkinsonism, acute dystonia, akathisia, tardive dyskinesias and rabbit syndrome. Rabbit syndrome is characterized by vertical rhythmic motion of the mouth and lips, resembling chewing movements of a rabbit.

Reason for the report

Rabbit syndrome seen in patients on antidopaminergic therapies is characterized by vertical rhythmic movements of perioral region, has a late onset, and characteristically spares the tongue. The main aim of the report is to highlight atypical manifestation of antipsychotic associated Rabbit syndrome in the presence of a serotonergic antidepressant.

Case summary

An elderly patient presented with atypical rabbit syndrome with relatively acute onset, horizontal movements of jaw and marked tongue involvement after haloperidol-escitalopram initiation.

Outcome

The patient improved with discontinuation of antipsychotic. The tongue involvement was believed to be secondary to escitalopram use.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at 10.1007/s40199-023-00489-5.

Introduction

Typical antipsychotics being antidopaminergics are known to produce extrapyramidal side effects such as drug induced parkinsonism, acute dystonia, akathisia and tardive dyskinesias [1]. Rabbit syndrome (RS) is another extrapyramidal condition that affects patients on antidopaminergic therapies. Around 2.3–4.4% of patients on typical antipsychotics may develop this condition though isolated reports of RS exist with atypical antipsychotics and antidepressant drugs [2, 3]. Rabbit syndrome is characterized by vertical rhythmic motion of the mouth and lips, resembling chewing movements of a rabbit. The onset of RS is usually late and occurs within months to years of underlying therapy. The movements seen are rapid, involuntary, occur at a frequency of nearly 5 Hz and are usually in the vertical plane [2]. Characteristically, tongue is spared in cases of RS, a feature that distinguishes it from tardive dyskinesias.

Reason for the report

To report the case of an elderly male on haloperidol and escitalopram who presented with atypical form of RS with relatively acute onset jaw tremor with horizontal movements and with conspicuous tongue involvement causing confusion in the diagnosis.

Case presentation

A 65-year-old man with newly diagnosed hypertension presented with abnormal movements of the jaw and tongue of 7 days duration, hampering his daily activities, and causing social embarrassment. Drug history revealed that he was taking amlodipine 10 mg daily for hypertension, haloperidol 0.25 mg twice daily and escitalopram 10 mg daily for insomnia for the past two months on the advice of a local medical practitioner. The course of the movements during sleep or under stress could not be confirmed as the patient lived alone. On examination, movements of around 5 Hz frequency and rhythmic in nature were present in the perioral area. Similar frequency tremor was evident in tongue. (Video 1, Supplementary material) Bradykinesia and rigidity were absent and there was no involvement of the trunk or extremities. Remaining neurological and other system examination were normal. In view of an extrapyramidal syndrome caused by haloperidol and absence of features of depression or anxiety, haloperidol was stopped, and oral trihexyphenidyl 2 mg thrice daily was started. The patient improved significantly in 10 days-time. (Video 2, Supplementary material). Trihexyphenidyl was eventually stopped after 3 weeks and clonazepam 0.5 mg on as needed basis was started for insomnia.

Discussion

The differentials considered in the current case were Rabbit syndrome (RS) and tardive dyskinesias (TD). The tongue is spared in classic cases of RS though rare cases of RS with lingual involvement exist [4]. The condition improves dramatically after drug discontinuation and administration of central anticholinergics. Dopaminergic drugs are generally not useful in Rabbit Syndrome [2]. Rabbit syndrome is often confused with tardive dyskinesias involving the orolabial region. In contrast to Rabbit syndrome, orolabial tardive dyskinesias are slower, less rhythmic, involve the tongue, and may have truncal and limb involvement. Onset of TD is also delayed, occurring after months to years of antipsychotic therapy, but the condition worsens with use of anticholinergics as opposed to Rabbit syndrome [5]. In the present case, the high frequency rhythmic chewing-like movement and rapid response to trihexyphenidyl administration closely resembled Rabbit syndrome. However, movements had a relatively acute onset and occurred within seven weeks of initiation of haloperidol, were more in the horizontal plane and were associated with tremors in tongue. Drug-induced Parkinsonism (DIP) was considered as another possibility in this case, but DIP usually starts within days to months of antipsychotic use and has other features such as bradykinesia and rigidity, which were absent in the present case [6].

Rabbit syndrome has clinical similarity with drug induced bruxism which is characterized by clenching of jaw, tooth grinding, jaw pain, jaw spasm, facial pain, headaches, and sleep disorders. Other than jaw tremor causing tooth grinding, no other feature suggestive of bruxism was present in the patient. Drug induced bruxism has been associated classically with anticonvulsants and antidepressants particularly the selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and sertraline, though cases exist with dopamine blockers also [7–9]. The condition usually requires cessation of culprit drug or addition of other neurological drugs with partial agonistic action on 5-HT1a receptors, such as buspirone [7]. No report to our knowledge exists of improvement of SSRI associated bruxism with trihexyphenidyl. Though the patient in present case was taking escitalopram which can mechanistically induce bruxism, the same was however not discontinued and the condition improved with trihexyphenidyl suggesting SSRI induced bruxism to be less likely in this case.

The exact pathogenesis of Rabbit Syndrome or similar extrapyramidal syndromes is unclear but disturbances in the movement circuits of basal ganglia in the form of acute dopamine blockade have been projected as possible mechanisms [2]. Among drugs received by the patient, chances of development of RS are more with haloperidol. The drug is a potent conventional antipsychotic agent with increased propensity to cause dopamine receptor blockade. However, the patient was also taking the antidepressant escitalopram which works via inhibition of serotonin reuptake and has alone been implicated in few cases of rabbit syndrome [3]. The drug has been associated with isolated tongue tremors which resolve spontaneously without drug discontinuation as was observed in the present case [10]. The third drug the patient had been on in the same time frame was amlodipine which is a L type calcium channel blocker, anti-hypertensive agent. Although otherwise safe, it has been associated with rare cases of new onset tremors mimicking DIP [11]. The association of amlodipine with rabbit syndrome and tongue tremors is not known at present. Though escitalopram and amlodipine were not stopped, a possibility of pharmacodynamic drug interaction with haloperidol resulting in atypical extrapyramidal manifestations cannot be excluded.

Though the patient in the current case did not have features completely matching any of the discussed extrapyramidal syndromes, the high frequency rhythmic chewing-like movement and rapid response to trihexyphenidyl administration more closely resembled Rabbit syndrome. The early onset of symptoms after two months of haloperidol therapy, movements more in the horizontal plane and the associated tongue involvement were atypical features of the case. The tongue involvement was believed to be secondary to escitalopram use.

Outcome

The syndrome resolved after discontinuation of haloperidol. Tongue tremor with serotonergic drugs resolves spontaneously as was noticed in this case.

Conclusion

Typical antipsychotic drugs such as haloperidol can produce atypical extrapyramidal features with concomitant serotonergic antidepressants. A thorough drug history of neurological as well as non-neurological drugs should be taken to delineate any synergistic or additive interaction that increases the vulnerability of an individual towards atypical extrapyramidal symptoms.

Funding

None.

Declaration

Conflict of interest

None