Incidence of Oculogyric Crisis and Long-Term Outcomes With Second-Generation Antipsychotics in a First-Episode Psychosis Program David M. Gardner, PharmD, MSc,*† Sabina Abidi, MD,*† Zenovia Ursuliak, MD, PhD,*† Jason Morrison, MD,*† Michael D. Teehan, MD,*† and Philip G. Tibbo, MD*† Abstract: Oculogyric crisis (OGC) is an often recurrent dystonic adverse effect of antipsychotic treatment characterized by a sustained fixed upward gaze lasting minutes to hours. The risk of OGC has not been established. We prospectively estimated the incidence rate of OGC in an early interven- tion service for psychosis and provided details regarding the antipsychotics implicated, clinical presentation, and long-term outcomes of OGC. The Nova Scotia Early Psychosis Program provides comprehensive, team-based care to youth and young adults with schizophrenia spectrum disorder. For 6 years (April 2008 to March 2014), 452 new patients were admitted to the pro- gram and participated in an individualized program of care. Eight patients (4 females; mean age, 19.8 years) developed recurrent episodes of OGC after 3 months to 2 years of treatment with 1 or more second-generation antipsychotics, yielding an incidence rate of 1.8% (95% confidence inter- val, 0.9%–3.4%). Risperidone or olanzapine (alone or in combination with a second antipsychotic) seemed causative in each case. Also implicated in the onset or recurrence of oculogyric episodes were ziprasidone, quetiapine, clozapine, aripiprazole, and the first-generation antipsychotic loxapine. Follow-up ranged between 2 and 7 years. Episodes stopped after switching antipsychotic treatment in 4 cases and after stopping anti- psychotic treatment in 2 cases. In the other 2 cases, recurrences were ongo- ing at last follow-up 2 and 6 years after onset with antipsychotic treatment continuing. We observed a high rate of tardive-onset, recurrent, and poten- tially chronic ocular dystonias in patients with first-episode psychosis caused by the use of second-generation antipsychotics. Key Words: oculogyric crisis, second-generation antipsychotics, tardive dystonia, first-episode psychosis, incidence (J Clin Psychopharmacol 2015;35: 715–718) R eported as an uncommon or rare adverse effect of antipsy- chotic agents and other dopamine antagonists, oculogyric cri- sis (OGC) is characterized by tonic, conjugate, and sustained ocular deviation, generally in the upward direction, with acute or tardive onset. 1–4 Episodes of OGC may last minutes to hours and can recur or become chronic, 1,5 with patients occasionally reporting prodromal symptoms preceding the OGC event such as restlessness, agitation, malaise, or fixed stare. Concurrent man- ifestations can include backward and lateral flexions of the neck, jaw opening, blepharospasm, tongue protrusion, and ocular pain. In addition, psychotic and other psychiatric symptoms have been observed to coincide with episodes of OGC in some patients. 6,7 Importantly, patients with OGC, especially when recurrent, ex- perience severe distress and are at risk of accidents and treat- ment refusal. The risk for extrapyramidal adverse effects and tardive dyski- nesia is lower for some second-generation antipsychotics, espe- cially quetiapine and clozapine. However, estimating the risk for OGC with any antipsychotic has proven difficult. Product mono- graphs indicate that OGC is a possible adverse dyskinetic effect with all second-generation antipsychotics. Cases of acute- and tardive-onset OGC have been reported with olanzapine, 8–12 quetiapine, 13 clozapine, 14–17 risperidone, 18–20 aripiprazole, 21–23 and ziprasidone. 24–26 Here, we estimate the incidence rate of OGC in an early intervention service for psychosis and provide details regarding the antipsychotics implicated, clinical presentation, and long-term outcomes of OGC. MATERIALS AND METHODS The Nova Scotia Early Psychosis Program (NSEPP), based in Halifax, Nova Scotia, Canada, is a multidisciplinary program that provides a comprehensive set of services and resources to youth and young adults aged 15 to 35 years in the early phase of a schizophrenia spectrum disorder and their families. Long-term follow-up care of up to 5 years is provided to patients admitted to the program. Consultation services are also provided. However, only admitted, long-term patients were included in this report. Pharmacological treatment is typically with second-generation anti- psychotics, with duration of treatment following clinical guidelines. Between April 2008 and March 2014, clinic staff prospec- tively identified patients in the program who experienced any form of OGC while on any antipsychotic treatment. Information was gathered from semistructured interviews with each patient, from clinical staff including psychiatrists, family physicians, and nurses, and from the patients' medical files. All patients gave writ- ten informed consent and the Research Ethics Board of the Capital District Health Authority approved publication of the results. RESULTS For the 6-year observation period, 452 new patients (mean age: 25 years; 32% female) experiencing first-episode psychosis were admitted to the adult (86.5%) and pediatric (13.5%) NSEPP clinics. Eight patients (4 females) experienced recurrent episodes of OGC, representing an incidence rate of 1.8% (95% confidence interval, 0.9%–3.4%). Patients experiencing OGC ranged in age from 15 to 24 (mean, 19.8) years at first onset of OGC, and all were treated with risperidone or olanzapine, alone or in combina- tion with a recently added second antipsychotic. Duration of anti- psychotic use before the first OGC episode ranged from 3 months to 2 years indicating nonacute onset in all cases. Follow-up of OGC outcomes ranged between 2 and 7 years after the initial presenta- tion. Episodes stopped after switching antipsychotic treatment in 4 cases (3, 4, 6, 8) and after stopping antipsychotic treatment in 2 cases (1, 5). In the other 2 cases (2, 7), OGC recurrences were From the *Department of Psychiatry, Dalhousie University; and †Nova Scotia Early Psychosis Program, Nova Scotia Health Authority, Nova Scotia, Canada. Received May 7, 2015; accepted after revision August 26, 2015. Reprints: David M. Gardner, PharmD, MSc, Rm 7517, Abbie Lane Building, QEII Health Science Centre, 5909 Veterans' Memorial Lane, Halifax, Nova Scotia, Canada B3H 2E2 (e‐mail: david.gardner@dal.ca). This study was supported by the Drug Evaluation Alliance of Nova Scotia, Department of Health and Wellness, Government of Nova Scotia. Supplemental digital contents are available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal's Web site (www.psychopharmacology.com). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0271-0749 DOI: 10.1097/JCP.0000000000000411 BRIEF REPORT Journal of Clinical Psychopharmacology • Volume 35, Number 6, December 2015 www.psychopharmacology.com 715 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.