Real-world Comparative Effectiveness of Long-acting Injectable and Oral Antipsychotics Among US Medicare Beneficiaries with Schizophrenia

Objective: Little real-world evidence exists comparing the benefits of long-acting injectables (LAIs) relative to daily oral antipsychotics (OAPs) in the Medicare population, which includes about half of US patients with schizophrenia. This study compared the effectiveness of LAIs and OAPs across different agents and dosing intervals
Methods: National fee-for-service Medicare claims from 2006-2019 were used to identify all beneficiaries with schizophrenia and ≥1 antipsychotic fill. The primary outcome was treatment failure, a composite measure of psychiatric hospitalization, antipsychotic discontinuation, suicide attempt, or death. Within-individual Cox regressions were used, in which each individual served as his or her own control to remove selection bias. Using LAI haloperidol as the comparator, we first compared outcomes across all LAI and OAP agents then separated the LAI agents by dosing intervals.
Results: The final sample included 152,835 beneficiaries (mean age 53.5 years, 54.0% male, 61.5% White). Compared to LAI haloperidol, all OAPs except clozapine, olanzapine, paliperidone, and fluphenazine and all LAIs except aripiprazole (HR 0.88; 95% CI 0.84-0.94), risperidone (HR 0.81; 95%CI 0.79-0.84), and paliperidone (HR 0.78; 95% CI 0.75-0.80) were associated with a significantly higher hazard (HRs 1.03 to 1.56) of treatment failure. When separating LAI agents by dosing interval, paliperidone LAI every 3-months (HR 0.55; 95% CI 0.49-0.62) had the lowest hazard of failure.
Conclusions: This real-world study found that most OAPs had a higher risk of treatment failure relative to LAI haloperidol. Several LAIs showed a greater benefit with paliperidone LAI every 3-monthls having the lowest risk of treatment failure.