Real-World Effectiveness of Long-Acting Injectable and Oral Antipsychotic Agents in US Medicare Patients with Schizophrenia

Introduction: Daily oral antipsychotics (OAPs) are the mainstay of schizophrenia treatment; however, long-acting injectable antipsychotics (LAIs) are associated with better treatment adherence and improved outcomes.

Methods: This study assessed the real-world comparative effectiveness of LAIs and daily OAPs using claims data from a nationally representative sample of fee-for-service Medicare beneficiaries with schizophrenia. Antipsychotic discontinuation, psychiatric hospitalization, and treatment failure were compared relative to different reference groups using within-individual Cox regression models.

Results: The study included 152,835 patients (mean age, 53.5 years; 54.0% male and 61.5% white). LAIs when grouped by dosing intervals were associated with significantly lower risk of antipsychotic discontinuation (hazard ratios [HRs] 0.27-0.69), psychiatric hospitalization (HRs 0.76-0.88), and treatment failure (HRs 0.55-0.74) compared with OAPs. When LAIs of different dosing intervals and OAPs were broken out by type of agent and compared with oral risperidone, second-generation LAIs, specifically LAI paliperidone (every 3 months [Q3M] and monthly [Q1M]), LAI aripiprazole (Q1M), and LAI risperidone (primarily every 2 weeks), had a significantly lower risk of antipsychotic discontinuation (HRs 0.19-0.67), psychiatric hospitalization (HRs 0.76-0.91), and treatment failure (HRs 0.53-0.85). Second-generation LAI paliperidone (Q3M) had the lowest risk for negative outcomes relative to OAPs; this effect was maintained when the reference group was changed to oral risperidone, LAI risperidone, LAI aripiprazole (Q1M), and LAI haloperidol (Q1M) (33-47% lower risk).

Conclusion: Efforts are needed to enhance identification of appropriate candidates for LAIs and increase their uptake, especially longer dosing interval LAIs, in the Medicare population.