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Comparative Study
. 2025 Feb;42(2):1251-1264.
doi: 10.1007/s12325-024-03075-6. Epub 2025 Jan 15.

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

Pengxiang Li  1 , Zhi Geng  1 , Carmela Benson  2 , Charmi Patel  2 , Jalpa A Doshi  3   4
Affiliations
Comparative Study

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

Pengxiang Li et al. Adv Ther. 2025 Feb.

Abstract

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.

Keywords: Comparative effectiveness; Efficacy; First- and second-generation antipsychotics; Hospitalization; Persistence; Real-world outcomes; Relapse; Schizophrenia; Treatment discontinuation; Treatment failure.

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Conflict of interest statement

Declarations. Conflict of Interest: Pengxiang Li reported receiving personal fees from Cobbs Creek Healthcare and SKB Consulting Inc, all unrelated to the submitted work. Zhi Geng has nothing to disclose. Carmela Benson and Charmi Patel reported being employees of Janssen Scientific Affairs, LLC and stockholders of Johnson and Johnson. Jalpa Doshi reported receiving grants from Janssen Scientific Affairs, LLC during the conduct of the study; personal fees from AbbVie, Acadia, Janssen, Merck, Otsuka, and Takeda; and grants from Merck and Spark Therapeutics unrelated to the submitted work. No other authors had disclosures to report. Ethical Approval: This study was conducted in accordance with the Helsinki Declaration of 1964 and its later amendments. The University of Pennsylvania Institutional Review Board deemed this study exempt from review.

Figures

Fig. 1
Fig. 1
Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for antipsychotic discontinuation during each treatment compared with oral risperidone use. aAlthough use of biweekly and monthly long-acting injectable (LAI) risperidone formulations was observed in our study, the vast majority (> 99%) of LAI risperidone use was for the biweekly formulation (i.e., every 2 weeks). bAlthough use of biweekly and monthly LAI olanzapine formulations was observed in our study, the vast majority (> 94%) of LAI olanzapine use was for the monthly formulation (i.e., Q1M). FGA first-generation antipsychotic, NA not available, QXM every X months, SGA second-generation antipsychotic
Fig. 2
Fig. 2
Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for psychiatric hospitalization during each treatment compared with oral risperidone use. aAlthough use of biweekly and monthly long-acting injectable (LAI) risperidone formulations was observed in our study, the vast majority (> 99%) of LAI risperidone use was for the biweekly formulation (i.e., every 2 weeks). bAlthough use of biweekly and monthly LAI olanzapine formulations was observed in our study, the vast majority (> 94%) of LAI olanzapine use was for the monthly formulation (i.e., Q1M). FGA first-generation antipsychotic, NA not available, QXM every X months, SGA second-generation antipsychotic
Fig. 3
Fig. 3
Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for treatment failure during each treatment compared with oral risperidone use. aAlthough use of biweekly and monthly long-acting injectable (LAI) risperidone formulations was observed in our study, the vast majority (> 99%) of LAI risperidone use was for the biweekly formulation (i.e., every 2 weeks). bAlthough use of biweekly and monthly LAI olanzapine formulations was observed in our study, the vast majority (> 94%) of LAI olanzapine use was for the monthly formulation (i.e., Q1M). FGA first-generation antipsychotic, NA not available, QXM every X months, SGA second-generation antipsychotic
Fig. 4
Fig. 4
Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for treatment failure during each treatment compared with alternative reference groups. aAlthough use of biweekly and monthly long-acting injectable (LAI) olanzapine formulations was observed in our study, the vast majority (> 94%) of LAI olanzapine use was for the monthly formulation (i.e., Q1M). bAlthough use of biweekly and monthly LAI risperidone formulations was observed in our study, the vast majority (> 99%) of LAI risperidone use was for the biweekly formulation (i.e., every 2 weeks). FGA first-generation antipsychotic, NA not available, QXM every X months, SGA second-generation antipsychotic
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