Oculogyric crisis with atypical antipsychotics: A case series

Abstract

Oculogyric crisis (OGC) is an acute dystonic reaction, commonly seen with the administration of typical antipsychotics, and rarely reported with atypical antipsychotics. Here, we report five cases of oculogyric crisis, developed after administration of atypical antipsychotics. The first case developed OGC on quetiapine 800 mg/day and the second case on olanzapine 20 mg/day. Both the patients did not improve on adding anticholinergic agents and finally stabilized by switching to clozapine. The third case developed OGC on amisulpride 400 mg and lurasidone 40 mg/day and improved by reducing amisulpride dose to 200 mg and stopping lurasidone. The fourth case developed OGC on aripiprazole 30 mg/day and improved by dose reduction. The fifth case developed OGC on amisulpride 400 mg/day and improved by switching to risperidone and anticholinergic combination. Oculogyric crisis is a potential side effect of antipsychotic medications (mostly with typical and rarely with atypical) and generally respond to oral anticholinergics, but in some cases, dose reduction or discontinuation of antipsychotic agent and switching to safer alternatives or clozapine is required.

INTRODUCTION

Oculogyric crisis (OGC) is an acute dystonic reaction characterized by spasmodic deviations of the eyes, most commonly upward, occasionally lateral, downward, or oblique, lasting for a few minutes to several hours, and usually associated with restlessness.[1] Acute dystonic reactions are seen commonly seen in young age, male gender, with use of high-potency typical antipsychotics, high dose, and parenteral drug administration.[2] OGC is rarely reported with atypical antipsychotics such as olanzapine,[3,4] quetiapine,[5] aripiprazole,[6,7] and amisulpride.[8] Here, we report presentation and management of five cases of oculogyric crisis caused by different atypical antipsychotic agents.

CASE REPORTS

Case 1

A 28-year-old young female with paranoid schizophrenia for the past 12 years had already received adequate trials of risperidone and olanzapine but with no respite. She was prescribed tablet haloperidol 10 mg/day along with 4 mg trihexyphenidyl (THP) to prevent extrapyramidal side effects (EPS), on which she reported partial improvement, so the dose was hiked up to 15 mg/day. However, within 15 days, she started having repeated episodes of uprolling of eyeballs with upward fixation along with anxiety, restlessness, and backward flexion of the neck, each episode lasted for 3–5 min. These episodes continued despite hiking the dose THP to 6 mg; therefore, haloperidol was stopped, and she was started on quetiapine. OGC episodes were completely stopped, after 7 days of haloperidol discontinuation. Thereafter, dose of quetiapine was gradually hiked to 800 mg/day. Approximately 1 month after haloperidol discontinuation and within 5 days of dose increment to 800 mg dose, she again started having similar OGC episodes, which were neither improved by decreasing the quetiapine nor with adding THP. Naranjo algorithm[9] indicated a probability score of 8 of haloperidol- and quetiapine-induced OGC. Thereafter, she was shifted on clozapine. At present, she is free from OGC and maintaining well on 450 mg of clozapine for the past 5 months.

Case 2

A 25-year-old young male with paranoid schizophrenia for 3 years, presented to us with a history of uprolling of eyeballs with haloperidol 20 mg/day and without any respite on adding 6 mg of THP. Hence, he was shifted on olanzapine 10 mg in the view of good efficacy and less EPS potential. The dose was hiked from 10 to 20 mg/day after 15 days as the patient had partial improvement. However, within 5–6 days of hiking the dose, he again started reporting repeated episodes of uprolling of eyeballs with upward fixation, each episode lasted for 5–6 min, and continued despite adding oral anticholinergic medication. Naranjo algorithm[9] indicated a probability score of 8, which clearly depicts probable association of oculogyric crisis with olanzapine. Thereafter, he was shifted on clozapine. At present, the patient is free from OGC and maintaining well on clozapine 500 mg for the past 5 months.

Case 3

A 29-year-old young male with a 5-year duration of paranoid schizophrenia and hypothyroidism on daily dose of thyroxin 150 mcg presented to us with partial improvement in psychotic symptoms with adequate trials of risperidone. We prescribed tablet amisulpride, and the dose was gradually hiked to 400 mg/day, and subsequently, he reported significant improvement in psychotic symptoms and functionality for nearly 1 year. However, later family members started reporting his mood swings, irritability, and rigid attitude at work and home. In addition to amisulpride 400 mg, lurasidone 40 mg/day was further added by a private psychiatrist. Nearly after 10 days of this combination, he started having episodes of uprolling of eyeballs with upward fixation and marked anxiety, which were difficult to bring back to original position by the patient, and each episode lasted for 15–20 min. These episodes improved after discontinuation of lurasidone and reducing the dose of amisulpride to 200 mg/day, but thereafter, he started having off/on agitation, anxiety symptoms, and sleep disturbances, for which quetiapine 100 mg was added. Naranjo algorithm indicated a probability score of 7, which clearly depicts probable association of oculogyric crisis with lurasidone and amisulpride. Now, the patient is stabilized on amisulpride 200 mg/day and quetiapine 100 mg/day and free from OGC episodes for the past 6 months.

Case 4

A 22-year-old young female with borderline personality disorder was initially treated with risperidone 4 mg/day but stopped after 1 year due to significant weight gain. Thereafter, she was shifted on aripiprazole 10 mg/day and gradually hiked to 30 mg/day, on which she reported significant improvement in mood symptoms, impulsivity, and aggression, but on the other hand, after 2 weeks of hiking the dose to 30 mg, she started having episodic uprolling of eyeballs and upward and lateral fixation of eyes, each episode lasted for 15–20 min, and OGC resolved after addition of THP 2 mg. Later, THP was stopped and the patient was stabilized without OGC recurrence on aripiprazole 20 mg/day. Naranjo algorithm indicated a probability score of 8, which clearly depicts probable association of oculogyric crisis with aripiprazole. Now, the patient is maintaining well on aripiprazole 20 mg/day and free from OGC episodes for the past 3 months.

Case 5

A 25-year-old young female with paranoid schizophrenia for 3 years showed partial improvement in psychotic symptoms with olanzapine 10 mg/day, but due to excessive sedation, she was switched on aripiprazole. On aripiprazole 15 mg/day, she reported tremors in hands, change in gait, and rigidity, which were not improved even after adding THP. Later, she was put on amisulpride in the view of its less sedative and metabolic side effects, and the dose was gradually hiked to 300 mg/day, on which she had significant improvement in psychotic symptoms and functionality for nearly 9 months. Thereafter, family members started reporting her poor interaction, irritability, and lesser functionality, so the dose of amisulpride was hiked to 400 mg/day. After 1 month, she started having episodes of uprolling of eyeballs with upward fixation and marked anxiety, which were difficult to bring back to original position by the patient, and each episode lasted for 10–20 min. These episodes improved after discontinuation of amisulpride and switching on risperidone 3 mg and THP 2 mg combination. Naranjo algorithm indicated a probability score of 8, which clearly depicts probable association of oculogyric crisis with amisulpride. Now, the patient is stabilized on risperidone 3 mg and THP 2 mg and free from OGC episodes for the past 1 year.

DISCUSSION

Acute dystonia such as OGC is generally related to initiation or hiking the dose of typical antipsychotics but rarely reported with atypical antipsychotics.[10] A prospective study of early intervention for psychosis reported 1.8% incidence of OGC in patients receiving atypical antipsychotics, and risperidone and olanzapine were common causative agents.[11] Index case series report five cases with OGC by different atypical antipsychotics. In all five cases, OGC diagnosis was made after thorough evaluation and exclusion of all possible differentials of organic and psychological disorders.

OGC associated with quetiapine is rarely reported,[5] due to its intermediate D2 receptor affinity and fast dissociation action.[12] Olanzapine in higher doses shows a higher D2 binding affinity,[13] which probably increases the risk of OGC.[3,4] Clozapine is an atypical antipsychotic and generally considered as an effective treatment in patients with tardive syndrome.[14] Our first two cases had a significant improvement in OGC after switching to clozapine therapy. Amisulpride, in dosages between 400 and 800 mg/day, results in antagonism of postsynaptic dopamine receptors.[15] Acute onset and tardive OGC has been reported with amisulpride.[8] Our third and fifth cases reported OGC with amisulpride and improved after dose reduction in previous case and with switching to risperidone + THP combination in later case. Aripiprazole has very low propensity for extrapyramidal side effects, with very rare report of OGC.[6,7] Our fourth case developed OGC with hiking the dose of aripiprazole, who became free from OGC on reducing the dose.

Sometimes, it is difficult to implicate any specific atypical antipsychotic for developing acute dystonic reaction as many patients have previous exposure of typical antipsychotics. Previous antipsychotic exposure might have priming effect on the striatum and underlying susceptibility with possible genetic predisposition. OGC generally responds to oral anticholinergics, but in troublesome cases, tapering or discontinuation of antipsychotic with switching to other safer antipsychotic is recommended. Clozapine is a choice agent with minimal propensity for EPS. For timely diagnosis and appropriate management of OGC, physicians must be aware of the varied presentation of OGC as recurrent dystonic reactions have obvious implications to medication adherence.

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Conflicts of interest

There are no conflicts of interest.