Long-Acting Injectables in Schizophrenia: Closing the Gap Between Evidence and Practice

CONFERENCE REPORTER

At the Southern California Psychiatry conference, Jacob Hanaie, PharmD, APh, BCPP, made the case that long-acting injectable (LAI) antipsychotics deserve a place much earlier in the treatment conversation for patients with schizophrenia.¹ LAIs are associated with substantially lower relapse and rehospitalization rates compared with oral antipsychotics, Hanaie, director of pharmacy at Kedren Acute Psychiatric Hospital & CMHC, told attendees. Yet fewer than 10% of patients with schizophrenia in the United States are currently prescribed one.

The Case for Rethinking Adherence

Relapse and repeated episodes in schizophrenia have been linked to progressive functional decline, and each recurrence raises the odds that a previously effective medication—or dose—will stop working as well the next time, he explained. That escalating cost is part of why Hanaie framed adherence as a crucial issue that requires attention.

Hanaie cited data indicating close to 70% of patients who are prescribed oral antipsychotics do not take them as directed.² “One thing is certain: Lack of efficacy is not the reason why patients are not taking medication,” he told attendees. Instead, he noted side effects, cognitive impairment or lack of routine are they key causes of nonadherence. In addition, he noted that adherence and nonadherence is not straight forward. “Adherence is partial,” he explained. “Adherence is dynamic. What you get the very first month or the second month might not look the same as what you would get the 6-month or the 12 month.” As a result, he believes nonadherence is underestimated in clinical practice.

Yet real-world data with LAIS flip that picture, Hanaie said. Analyses show adherence rates roughly 89% higher with LAIs compared with oral formulations, alongside a 26% to 45% reduction in treatment failure.³ "Despite these numbers—almost 90% reduction in relapse or adherence improving—only about 10% of the patients are on long acting injection," Hanaie said. He added this is unique to the US and that other countries have made considerably more progress on this front.

Part of the value of LAIs, Hanaie explained, goes beyond adherence numbers. Steadier plasma exposure avoids the peak-and-trough pattern common with daily oral dosing. A missed injection becomes visible to the care team immediately, rather than surfacing weeks later as a widening gap in pill counts. He pointed to a benefit that extends beyond the patient: LAIs mean fewer daily medication-related conflicts between patients and the family members or caregivers around them.

A Broader Menu Than a Decade Ago

The LAI landscape has grown considerably from the days when risperidone's Risperdal Consta stood alone, Hanaie told attendees. Four molecule medications are now available in LAI form, each with meaningfully different practical profiles, allowing for a customized menu for the clinician and their patient.

For instance, aripiprazole is available in 3 formulations spanning from monthly to every-8-week dosing. Aristada, a nonester prodrug, offers more flexibility in strength and interval than its counterparts, and an initiation option (Aristada Initio) now allows same-day dosing without the extended oral supplementation the product once required, he explained.

Meanwhile, paliperidone follows a step-up model in which patients must first demonstrate stability on the monthly formulation (Sustenna) before graduating to the quarterly (Trinza) or twice-yearly (Hafyera) options, he said. A newer entrant, Erzofri, uses the same molecule but skips the standard second loading injection.

Risperidone's LAI options now range from the original Consta with biweekly injections and medication that requires refrigeration to Uzedy, a subcutaneous formulation that needs no oral supplementation, carries no loading-dose requirement, and can be stored at room temperature for up to 90 days, Hanaie added.

Olanzapine remains effective but constrained, he said. Its only current LAI, Relprevv, carries a REMS requirement and mandatory 3-hour post-injection monitoring due to postinjection delirium/sedation syndrome (PDSS) risk. However, he noted that may soon change, with TEV-749, a subcutaneous olanzapine LAI, under FDA review after the agency accepted its New Drug Application in February 2026. The SOLARIS trial reported significant symptom improvement with no PDSS cases, and the drug carries no REMS requirement. Its Prescription Drug User Fee Act target action date falls in the fourth quarter of 2026.

Given that range of options, Hanaie's organizing advice for clinicians was to sequence the decision deliberately: pick the right molecule for the patient first, then select the delivery system. Duration, route, and initiation logistics matter, he said, but they are secondary decisions, not the starting point.

Overcoming Barriers and Obstacles

If the evidence favors broader LAI use, the barriers are more about practice than proof, according to Hanaie. He pointed to a conservative approach embedded in treatment guidelines and uneven awareness of the newer formulations among clinicians. On the patient side, needle anxiety is real, as is context, as LAIs have been experienced as punitive when administered in acute or involuntary settings. This framing needs to be corrected and separated from how LAIs are introduced in ongoing outpatient care, he added.

Physician hesitation compounds the problem, he said. Clinicians who assume a patient will decline an LAI may present it half-heartedly, which can become self-fulfilling. Logistical friction, including prior authorization, storage requirements, staff comfort with gluteal administration, missed-dose protocols, adds further drag, although none of it is insurmountable with the right systems in place, he said.

The Conversation Matters Most

With evidence supporting LAI use, the conversations about it matter even more, Hanaie told attendees. “The most persuasive LAI counseling is transparent about the benefits, falsehoods, and limitations,” he shared. “The conversation is what determines whether the option becomes acceptable or not.”

Learn more about prescribing LAIs in schizophrenia at the inaugural Jersey City Psychiatry Conference in October 2027.

References

1. Hanaei J. Optimizing Adherence for Patients With Schizophrenia. Presented at the 2026 Southern California Psychiatry Conference.

2.Haddad PM, Brain C, Scott J. Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies. Patient Relat Outcome Meas. 2014;5:43-62.

3. Kane JM, Agid O, Castle DJ, et al. The Use of Long-Acting Injectables for People with Schizophrenia: Consensus Panel Recommendations for Overcoming Barriers and Implementing Treatment. Neurol Ther. 2025;14(6):2551-2581.