Comparative effectiveness of risperidone long-acting injectable vs first-generation antipsychotic long-acting injectables in schizophrenia: Results from a nationwide, retrospective inception cohort study

Abstract

Objective: To compare in a generalizable sample, setting objective outcomes in patients receiving first-generation antipsychotic long-acting injectables (FGA-LAIs) or risperidone- LAI (RIS-LAI). Methods: Nationwide, retrospective inception cohort study of adults with International Classification of Diseases-10 schizophrenia using Danish registers from 1995 to 2009 comparing outcomes between clinician's, patient's choice treatment with FGA-LAIs or RIS-LAI. Primary outcome was time to psychiatric hospitalization using Cox-regression adjusting for relevant covariates. Secondary outcomes included time to allcause discontinuation and psychiatric hospitalization in patients without LAI possession gap >28 days, and number of bed-days after psychiatric hospitalization. Results: Among 4532 patients followed for 2700 patient-years, 2078 received RIS-LAI and 2454 received FGA-LAIs (zuclopenthixol decanoate = 52.2%, perphenazine decanoate = 37.2%, haloperidol decanoate = 5.0%, flupenthixol decanoate = 4.4%, fluphenazine decanoate = 1.3%). RIS-LAI was similar to FGA-LAIs regarding time to hospitalization (RIS-LAI = 246.2 ± 323.7 days vs FGALAIs = 276.6 ± 383.3 days; HR = 0.95, 95% confidence interval (CI) = 0.87-1.03, P = 0.199) and time to all-cause discontinuation (RIS-LAI = 245.8 ± 324.0 days vs FGALAIs = 287.0 ± 390.9 days; HR = 0.93, 95% CI = 0.86-1.02, P = 0.116). Similarly, in patients without LAI discontinuation, RIS-LAI and FGA-LAIs did not differ regarding time to hospitalization (RIS-LAI = 175.0 ± 268.1 days vs FGALAIs = 210.7 ± 325.3 days; HR = 0.95, 95% CI = 0.86- 1.04, P = 0.254). Finally, duration of hospitalization was also similar (incidence rate ratio = 0.97, 95% CI = 0.78- 1.19, P = 0.744). Results were unchanged when analyzing only patients treated after introduction of RIS-LAI. Conclusions: In this nationwide cohort study, RIS-LAI was not superior to FGA-LAIs regarding time to psychiatric hospitalization, all-cause discontinuation, and duration of hospitalization. Given the cost of hospitalization and second- generation antipsychotic (SGA)-LAIs, these findings require consideration when making treatment choices, but also need to be balanced with the individual relevance of adverse effects, patient centered outcomes. In future, headto- head trials and additional nationwide database studies including other SGA-LAIs is needed.