Long-Term Continuity of Antipsychotic Treatment for Schizophrenia: A Nationwide Study

Abstract

Background: Schizophrenia often requires long-term treatment with antipsychotic medication. This study aims to measure the continuity of antipsychotic treatment over the course of illness in schizophrenia, as well as factors involved in the interruption of treatment. Methods: Cohort study of individuals in Finland recently diagnosed with schizophrenia, and followed up between 2000 and 2018. Stratified Cox proportional hazards regressions were conducted for “within-participant” risk of discontinuation of subsequent treatments compared to the first, and by specific antipsychotic compared to oral olanzapine, the most commonly prescribed antipsychotic. Adjusted Hazards Ratios (aHR), 95% Confidence Intervals (95%CI) were calculated. Outcomes: Among 3,343 participants followed up for a mean of 8 years (Standard Deviation (SD)=4·93), the median number of continuous treatment episodes was 6 (Inter Quartile Range [IQR]=3-11) with a median duration of 11·4 months (IQR=5·3-25·6). In the first year after diagnosis, the incidence rate of treatment discontinuation was 30·12 (95%CI=29·89-30·35) events per 100 participant-years, decreasing to 8·90 (95%CI=8·75-9·05) in the tenth year. The risk of discontinuation progressively decreased over successive treatment episodes (aHR= 0·30; 95% CI=0·20-0·46 for episodes after the 15th compared to the 1st). Individuals were 67% less likely to interrupt treatment with long-acting injectable than oral antipsychotics (aHR=0·33; 95% CI=0·27-0·41). Interpretation: Treatment for schizophrenia over the long-term is often characterized by recurrent cycles of interruptions and reintroductions of antipsychotic medication, which is typically not recommended by management guidelines. Interventions in the early phase of illness and greater utilization of long-acting injectable formulations may facilitate the continuity of antipsychotic treatment in schizophrenia. Funding Statement: This study was funded with departmental support of the Zucker Hillside Hospital (Glen Oaks, NY), the Department of Clinical Neuroscience, Karolinska Institutet (Stockholm, Sweden), and the Academy of Finland (Grants: 315969, 320107, for HT). Declaration of Interests: Dr Rubio has been a consultant or has received speaker/consulting honoraria from: Lundbeck, Teva, Medscape. He has also received royalties from UpToDate, and grant support from Alkermes. Dr Taipale reports personal fees from Janssen-Cilag. Dr. Correll has been a consultant and/or advisor to or has received honoraria from: Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, IntraCellular Therapies, Janssen/JJ is a member of advisory board for Lundbeck, and has received grants from the Stanley Foundation and Sigrid Juselius Foundation. Dr. Tiihonen, Dr. Tanskanen and Dr. Taipale have participated in research projects funded by grants from Janssen-Cilag and Eli Lilly to their employing institution. Ethics Approval Statement: Permissions were granted by pertinent institutional authorities at the Finnish National Institute for Health and Welfare (permission THL/847/5.05.00/2015), the Social Insurance Institution of Finland (65/522/2015), and Statistics Finland (TK53-1042-15).