F113. LONG-TERM PHYSICAL HEALTH AND MORTALITY OUTCOMES OF PATIENTS WITH SCHIZOPHRENIA WITH CLOZAPINE AUGMENTATION WITH ANTI-PSYCHOTIC DRUGS

Abstract

Background: About a third of schizophrenia patients would not have sufficient clinical response to antipsychotic treatment. The only drug approved for this population is clozapine, yet worldwide reports suggest underuse of clozapine and significant delay in initiating treatment. Moreover, as a robust clinical response is evident in only about half of patients treated with clozapine, the common practice is to augment the compound with another antipsychotic compound. However, little is known about the nature of this augmentation and the outcome in real-world setting. In this study, we aimed to explore in a real-world database, the details of clozapine use in patients with schizophrenia and the use of augmentation with other compounds as well as to explore the outcome of this augmentation in relation to physical health, medical care utilization, and mortality. Method(s): A retrospective cohort study of "Clalit Health Services" electronic records. People diagnosed with schizophrenia (F.20 ICD 10 code) and had at least one prescription filled for clozapine were followed up between 2012 and 2014. Result(s): of 28,983 people diagnosed with schizophrenia, clozapine was prescribed and purchased by 1817 (6.5%) patients during the study period. Of them, 60% had polypharmacotherapy with another antipsychotic compound or lithium. The most prevalent augmentation was with sulpride (28%), perphenazine (17%) and zuclopenthixole (14.3%). Levels of physical comorbidity (metabolic and cardiovascular) were similar among groups (clozapine monotherapy vs. augmentation). However, polytherapy was associated with HR of 2.1 for mortality during the follow-up period. High mortality rate, during follow-up, was associated with haloperidol augmentation (12%) and sulpride (11.2%). Patients with augmentation were more referred to general emergency department and hospitalization while using similar rate of primary medical services as patients with clozapine monotherapy. Discussion(s): Clozapine is under-utilized in Israel and data suggests that when treatment is given it is not optimized as reflected by high rates of polytherapy. This real-world practice is associated with increased mortality and higher use of tertiary medical service although patients had similar levels of metabolic and cardiovascular morbidity and similar primary medical service utilization rate. This data suggests that considering augmentation of clozapine with another antipsychotic compound should be done cautiously and after careful consideration of clozapine optimization.