Length Matters in Schizophrenia Treatment: Research Shows Benefits of Long-Acting Injectable Treatments

The AMCP Nexus 2025 meeting last week in National Harbor, Maryland, featured cutting-edge managed care pharmacy research and presentations. There were a handful of schizophrenia posters that discussed real-world data, treatment optimization, and healthcare delivery. Below are some highlights of two posters.

A persistent challenge in schizophrenia care and managed care decision-making involves patient adherence and persistence on antipsychotics. Adherence is the Achilles’ heel of schizophrenia treatment. Nonadherence rates with oral antipsychotics can exceed 50%, leading to relapses, hospitalization and functional decline.

Long-acting injectables (LAIs) were designed to solve this problem by reducing the burden of daily pill-taking and ensuring more consistent drug exposure. Underutilization of LAIs in the U.S is common, despite guideline support. LAIs remain underprescribed due to cost, stigma, provider hesitancy, and logistical barriers.

There is also an evidence gap in newer LAIs. Much of the older literature focused on first-generation LAIs or small cohorts so a need arose for comparative effectiveness data. Payers and clinicians need robust, real-world comparisons of LAIs vs. oral agents to justify broader adoption and coverage.

The poster titled “Discontinuation of Long-Acting Injectable vs Oral Antipsychotics in U.S. Patients with Schizophrenia: A New-User Survival Analysis” from the University of Minnesota College of Pharmacy was a new-user survival analysis comparing LAI versus oral antipsychotic discontinuation rates in U.S. schizophrenia patients.

The Minnesota researchers relied on MarketScan claims data from 2020 to 2022 to investigate nearly 3,000 people starting therapy after a six-month washout. After balancing variables, LAI patients had a median time to discontinuation of 195 days compared to 133 days for oral medicines.

LAIs reduced discontinuation risk by 21%, and subgroup analyses showed comparable outcomes even without clozapine or first-generation antipsychotics. These data suggest that LAIs may increase schizophrenia care adherence and promote formulary coverage and clinical adoption to address treatment continuity issues.

Another poster presented at that meeting, titled “An Economic Model Assessing Costs, Relapses, and Antipsychotic Adherence of Switching Medicaid Beneficiaries With Schizophrenia From Oral Antipsychotics to Once-Monthly, Once-Every-Three-Months, and Once-Every-Six-Months Paliperidone Palmitate,” explored how economic modeling can bring visibility into both clinical and financial implications of treatment choices in schizophrenia. Johnson & Johnson, which makes several paliperidone palmitate products, sponsored the research.

The economic model discussed in the poster examined the effects of moving Medicaid schizophrenia patients from oral antipsychotics (OAPs) to long-acting paliperidone palmitate. A Medicaid payer-focused 36-month model compared three cohorts: patients on OAPs, those on once-monthly paliperidone palmitate and those on longer-interval formulations (every three and six months).

In a one-million-member simulated health plan, 13,419 schizophrenia patients treated with OAPs spent $1.25 billion, had 33,671 relapses, and adhered 69.5%. Switching 20% of patients to once-monthly paliperidone palmitate saved $106.2 million, prevented 4,349 relapses and improved adherence to 76.9%.

Transitioning to paliperidone palmitate every three months and paliperidone every six months saved $116.1 million, reduced relapses by 4,999, and increased adherence to 85.4%. Extended-interval formulations saved $9.9 million, averted 650 relapses, and improved adherence by 8.5% over once-monthly paliperidone palmitate alone.

This model shows that switching from OAPs to paliperidone palmitate, especially with longer-acting formulations, can save Medicaid a lot of money, make people more likely to stick with their treatment, and lower the number of relapses.

This modeling and data help add to the limited evidence in support of economic justification for LAIs in the Medicaid population. They also add to the expanding body of research that shows that expanded coverage of LAIs can improve outcomes while cutting costs.