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

Abstract

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. For this, we followed up a national cohort of first-episode psychosis patients in Finland for up to 18 years. 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 prescribed antipsychotic in this cohort. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated. Among 3343 participants followed up for a mean of 8 years (SD = 4.93), the median number of continuous treatment episodes was 6 (interquartile 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 10th 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 first). Individuals were 67% less likely to interrupt treatment with long-acting injectable than oral antipsychotics (aHR = 0.33; 95% CI = 0.27-0.41). 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. Greater utilization of long-acting injectable formulations earlier in the course of illness may facilitate the continuity of antipsychotic treatment in schizophrenia.

Keywords: course of treatment; pharmacoepidemiology; treatment discontinuation.

Fig. 1.

Risk of treatment discontinuation per year within the first decade since diagnosis, (A) among all, (B) stratified by duration of the first hospital stay (in months) due to schizophrenia.

Fig. 2.

Risk of treatment discontinuation during monotherapy compared with oral olanzapine in a within-individual analysis. 95% CI, 95% confidence interval;AHR, adjusted hazard ratio; FG, first generation; LAI, long-acting injectable; SG, second generation.

Fig. 3.

Risk of treatment discontinuation in head-to-head comparison of LAIs vs their oral counterparts in a within-individual analysis. 95% CI, 95% confidence interval; AHR, adjusted hazard ratio; LAI, long-acting injectable.