Clozapine-Induced Oculogyric Crises

Abstract

TO THE EDITOR: Atypical antipsychotics are less likely than first-generation antipsychotics to induce dystonic reactions. In particular, clozapine has rarely been reported to induce dystonic reactions 1 ; indeed, it has been reported to ameliorate dystonia. 2 Oculogyric crisis, which is a specific type of dystonic reaction, has been reported to occur during clozapine treatment 3 and upon clozapine discontinuation. 4 We report 2 episodes of oculogyric crisis.Case Report. A 37-year-old Indian man with chronic paranoid schizophrenia was admitted to a closely supervised inpatient unit, owing to severe psychotic symptoms. One year prior to admission, he had received therapy with depot fluphenazine. During the months leading up to admission, he had been treated with a combination of risperidone 8 mg/day, trifluoperazine 5 mg/day, amisulpride 200 mg/day, and trihexyphenidyl 6 mg/day orally. This antipsychotic polypharmacy regimen provided limited therapeutic benefit and induced prominent and persistent nondystonic extrapyramidal symptoms (EPS).The 3 antipsychotics were discontinued simultaneously and abruptly upon the patient's admission, but trihexyphenidyl was continued at a reduced dose of 4 mg/day. Without any washout period, clozapine was initiated at 25 mg/day and was gradually titrated upward. Within a few days, EPS resolved completely. Suddenly, 9 days later, the patient experienced a witnessed episode of oculogyric crisis (clozapine dosage 150 mg/day), which was successfully treated with 50 mg of intramuscular promethazine.Because the patient suffered from constipation, the decision was made to gradually discontinue trihexyphenidyl over a 2 week period. Within 48 hours of such discontinuation, he experienced a second episode of oculogyric crisis (on day 25 of clozapine monotherapy; clozapine dose 150 mg/day), which again responded to promethazine. In neither of these 2 oculogyric crises did immediate and follow-up clinical examinations reveal changes in the patient's mental or neurologic status. By the time the second event occurred, his psychopathology was showing moderate improvement.Discussion. It seems unlikely that these reactions were related to the residual effects of the patient's previous antipsychotic drugs. The oral medications had been discontinued 9 days prior to the first incident and 25 days prior to the second. Moreover, he had not received depot fluphenazine for more than a year. It is also unlikely that he was taking any other medications or substances during the hospitalization, given that he was under close supervision. Thus, clozapine appears to be the cause of the oculogyric crises. This viewpoint is consistent with the Naranjo probability scale, which indicates a probable relationship between the oculogyric crises and clozapine pharmacotherapy. 5 Interestingly, anticholinergic agents have been used to treat rare cases of clozapine-induced dystonic reactions, 3 but our patient experienced oculogyric crisis while receiving an anticholinergic agent. Another episode of oculogyric crisis occur...

Oculogyric crises: A review of phenomenology, etiology, pathogenesis, and treatment

“…Of medications associated with OGC, DRBAs have been the most extensively implicated. These include typical antipsychotics such as haloperidol and phenothiazines, atypical antipsychotics including sulpiride, risperidone, ziprasidone, olanzapine, aripiprazole, and clozapine, and antiemetics with action at dopamine receptors (e.g., metoclopramide) . OGC have been repeatedly described after exposure to the antiepileptic drugs (AEDs), carbamazepine (CBZ) and lamotrigine (LTG) …”

Oculogyric Crisis with Clozapine: A Case Report and Review of Similar Case Reports in the Literature

“…Similar to Uzun and Doruk,[ 4 ] our patient had experienced tardive OGC 1 year after starting clozapine at 300 mg dose, while other cases have reported acute OGC at 1 st month of clozapine therapy at 150 mg dose. [ 2 6 ]…”

“…Clozapine is an atypical antipsychotic and generally considered to have low risk of causing tardive syndromes and considered as an effective treatment in patients with tardive syndrome. [ 1 ] Oculogyric crisis (OGC) is one of the specific dystonic reactions, rarely reported with clozapine treatment[ 2 3 4 5 6 ] as well as on clozapine discontinuation. [ 7 ] We hereby present a case of OGC with clozapine therapy and review of literature.…”

Oculogyric crises: Etiology, pathophysiology and therapeutic approaches

“…In cases of tardive OGCs the aforementioned agents might be insufficient and long-term treatment with (atypical) neuroleptics such as clozapine might be required [124,125]. However, it should be noted that treatment effects might be limited in tardive OGCs, as substances such as clozapine themselves may also cause OGCs [126][127][128].…”