Aripiprazole-induced tardive blepharospasm: a case report

We report a case of a patient developing tardive dyskinesia (TD) as tardive blepharospasm after treatment with aripiprazole. A 22-year old-woman with a background diagnosis of bipolar affective disorder was treated with aripiprazole and subsequently developed tardive blepharospasm. This symptom resolved after switching to quetiapine. This report highlights the rare side effect of the development of tardive blepharospasm with aripiprazole. 

Case presentation

The woman was first diagnosed with bipolar affective disorder at the age of 17. She was in the US, where she developed manic symptoms. She presented with increased energy, poor sleep, irritability and paranoid delusions. She was also disinhibited, posting compromising pictures online. 

After a brief admission in the US, she returned to Ireland to her family and was admitted to the paediatric ward in a general hospital. Her condition stabilised without the need to transfer to an inpatient psychiatric unit.  

Following initial presentation she was commenced on aripiprazole which was worked up to a dose of 20mg/day. She took this daily for three years with no side effects. During the Covid-19 pandemic, she reported excessive blinking. She reported that it was difficult for her to open her eyes secondary to the spasms. She reported trying to open her eyes with her hands, but it was difficult to maintain. The spasms would last for a few seconds and recur every 30 seconds. She said that she could not control this movement nor did she experience any urge to induce the movement. 

We conducted a literature search on aripiprazole side effects as she was not on any other medication known to cause said symptoms, including anticholinergic medication. In the context of her symptomatology her reviews were face to face rather than phone consultation as was common during Covid times. She had neither a history of blepharospasm nor movement disorders prior to this presentation. 

In her personal history, there were no birth complications or delayed developmental milestones. Her childhood was unremarkable. She completed her Leaving Certificate and then a course in hospitality management and beauty therapy. She was unemployed at the time of presentation which she attributed to Covid restrictions. She was single at the time of presentation. There was no history of alcohol or illicit substance use issues.

She lived with her father and stepmother, and two stepbrothers. Her mother and maternal grandfather both had a diagnosis of bipolar affective disorder

On Mental State Examination (MSE), she was concerned with the excessive blinking and had difficulty maintaining eye contact during the interview. She did not report experiencing paranoid or psychotic symptoms. She reported safety concerns as a consequence of excessive blinking. For example, she felt it was unsafe to cross the street and reported that she was distressed by her inability to watch TV secondary to her excessive blinking

She was referred to neurology. Physical examination revealed involuntary contraction of the eye lids every few seconds and it was difficult for her to keep her eyes open for more than 10 seconds. There was no twitching in her neck or hands, no axial rigidity, no other involuntary movements, no motor impersistence and no nystagmus was observed. Her external eye movement and gait analysis were normal. Routine blood investigation results were also normal. 

The neurologist’s impression after examination was medication induced blepharospasm secondary to aripiprazole. Aripiprazole was discontinued and she was commenced on quetiapine (worked up to a dose of 300mg/day) for the alleviation of tardive symptoms with good effect. This led to the resolution of blepharospasm. There has been no recurrence of blepharospasm or any form of tardive dyskinetic symptoms with quetiapine use.

Discussion

This case highlights how patients can develop symptoms of tardive blepharospasm as a side effect of aripiprazole. This prompted neurological referral and a literature search.

In 1887 Horatio C Wood first described blepharospasm as a movement disorder characterised by hyperactivity and involuntary contraction of the orbicularis oculi and of other muscles around the eyes resulting in increased rate of eyelid closure. He noted: “The facial convulsions are in some cases limited to isolated muscles; the orbicularis palpebrarum is especially prone to suffer, giving rise to the affection known as blepharospasm…The contraction is tonic, causing a complete closure of the eye, and consequent blindness. This is accompanied by innumerable bizarre grimaces, due to the efforts of the antagonistic muscles to overcome the force which is closing the lids.”¹

Known as tardive blepharospasm, blepharospasm can be the only manifestation of neuroleptic-induced tardive syndrome, which is recognised as a movement disorder characterised by either sustained or intermittent contraction of a muscle.^2,3 Prevalence studies highlight that blepharospasm is a rare side-effect with a range of one in 50,000 to one in 10,000.⁴ It mostly affects women⁵ and the older population, with peak age between 50 and 70 years of age.⁶ Drug-induced blepharospasm is most commonly associated with antipsychotics,⁷ as well as dopaminomimetic drugs.⁸

While little is known about the pathophysiology of tardive blepharospasm, long-term use of antipsychotics is postulated to cause an imbalance of D1 and D2 receptors as leading to thalamofrontal pathway disinhibition.^7,9 Despite limited data on specific antipsychotic-induced tardive blepharospasm, several cases of drug-induced blepharospasm have been reported.^2,10,11

Second generation antipsychotics have fewer extrapyramidal side effects, which can be attributed to either a weak dopamine D2 receptor binding affinity or a strong antagonistic effect on serotonin 5-HT2a receptor.¹²

As a second generation antipsychotic, aripiprazole is used for the management of psychosis in patients with a variety of diagnoses. It can be used as monotherapy, adjunctive therapy and maintenance in the management of major depressive disorder or acute manic episodes associated with bipolar disorder.^13,14

Given its putative side-effect profile, aripiprazole use has increased compared to first generation antipsychotics. As a dopamine partial agonist, they are weight-sparing agents and are less likely to induce dopamine supersensitivity. Moreover, by regulating dopamine neurotransmitters, the motor and metabolic side-effects are less when compared to other antipsychotics which make it more favourable.^15,16

There is evidence for the use of quetiapine in the treatment of movement disorders.¹⁷ The exact mechanism is yet to be identified. It is suggested that similar to clozapine, quetiapine can downregulate the D2-receptor density in the striatum, by stimulating dopamine efflux.¹⁸ Moreover, quetiapine blocking 5-HT2- and H1-receptors rather than dopamine receptors was also thought to suppress symptoms.¹⁹

Some studies advocate for the switch to aripiprazole citing improvement in symptoms of tardive dyskinesia in patients previously treated with other neuroleptics.^20,21 Other reports suggest that the use of aripiprazole may also have a tendency to develop a tardive movement disorder whether it is used as monotherapy or adjunctive therapy.^22,23

Conclusion

Studies highlighting the link of drug-induced movement disorders associated with the use of psychotropic medication emphasise the need for early detection and management as well as gaining a better understanding of factors such as pathophysiology and risk factors associated with their use.²⁴ We hope that this case will draw attention to the potential risk of tardive blepharospasm during aripiprazole monotherapy.

Reference

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