Quetiapine treatment of occulogyric crisis following abrupt clozapine discontinuation

To the Editor,

Occulogyric crisis is an extra-pyramidal side effect of antipsychotic medications, more marked with conventional antipsychotics. Clozapine is known for its extremely low propensity for extra-pyramidal side effects, and is, in fact, used in their treatment at times. We report the occurrence of occulogyric crisis, following abrupt discontinuation of clozapine, and its management.

A young male, with schizophrenia since 8 years, presented to our center with complaints of persisting auditory hallucinations and persecutory delusions, despite regular treatment. He had been treated with different antipsychotics in adequate doses and duration. He developed occulogyric crisis, with Risperidone (up to 8 mg/day) and Trifluperazine (up to 20 mg/day), which was successfully treated with addition of Trihexyphenidyl. Due to poor response and adverse effects, he was started on Quetiapine (up to 600 mg/day) with some improvement in symptoms; however, auditory hallucinations persisted and the patient reported excessive sedation and lethargy. Thus, the patient was switched to Aripiprazole (up to 30 mg/day). Sedation reduced but auditory hallucinations persisted. Considering poor response to several antipsychotics, Clozapine was added, to Aripiprazole, with appropriate monitoring for side effects. The patient reported a decrease in frequency and duration of auditory hallucinations within a week of starting clozapine. However, at 100 mg/day Clozapine, the patient developed eosinophilia (Absolute Eosinophil count: 11,800/mm³) due to which clozapine was immediately discontinued. On the second day, the patient developed severe occulogyric crisis, which lasted for a few hours. Interestingly, this stopped after the patient self-medicated with Quetiapine 200 mg (from his old stock of medications). For the next 1 week, he continued Quetiapine 200 mg/day, with no further occulogyric crisis episodes.

A literature search using Medline revealed a single case report on development of occulogyric crisis following abrupt discontinuation of clozapine (Mendhekar and Duggal, 2006). The authors of this case report hypothesize that a rebound cholinergic excess, resulting in imbalance in the dopamine–acetylcholine cross-talk in the basal ganglia could explain occulogyric crisis following abrupt discontinuation of clozapine. Like Clozapine, Quetiapine too has a very low risk profile for extra-pyramidal side effects and has been used in the management of occulogyric crisis (Gourzis et al., 2007; Ghosh et al., 2013). With obvious limitations in conclusive interpretation, our case highlights an aspect of the clinical relevance of anti-cholinergic properties of clozapine and quetiapine.