New Schizophrenia Treatment Addresses Long-Standing LAI Barriers

The FDA's recent approval of olanzapine (WELTRUZA; Teva Pharmaceuticals) for extended-release injectable suspension introduces the first once-monthly subcutaneous formulation of the antipsychotic for adults with schizophrenia, offering clinicians a new long-acting treatment option that does not require oral supplementation, loading doses, or post-injection observation.¹

The approval, announced October 9, 2026, was supported by results from the phase 3 SOLARIS clinical development program, which demonstrated improvements in schizophrenia symptoms, illness severity, and personal and social functioning. The treatment is available in 3 once-monthly doses—318 mg, 425 mg, and 531 mg—corresponding to oral olanzapine doses of 10 mg, 15 mg, and 20 mg daily, respectively.¹

Unlike the previously available intramuscular long-acting olanzapine formulation, which requires 3 hours of post-injection observation because of the risk of post-injection delirium/sedation syndrome (PDSS), the new subcutaneous formulation does not require post-injection monitoring. However, the FDA prescribing information notes that it is not known whether PDSS can occur with subcutaneous olanzapine.²

The new formulation also carries the established safety considerations associated with olanzapine, including weight gain and metabolic abnormalities, underscoring the importance of ongoing monitoring and individualized treatment decisions.²

To discuss the clinical implications of the approval, Patient Care Online spoke with Christoph Correll, MD, clinical professor of psychiatry at the Zucker School of Medicine at Hofstra/Northwell and principal investigator of the SOLARIS program. Correll discussed how the new formulation may address treatment adherence, the importance of preventing relapse, findings from the SOLARIS program, and which patients may benefit most from once-monthly olanzapine.

The following Q&A has been edited for clarity and length.

Patient Care Online: Olanzapine has been a foundational schizophrenia treatment for more than 30 years, but adherence remains a major barrier to stability. Why has it taken this long to develop a practical long-acting olanzapine option, and what treatment gap does the new formulation fill?

Correll: Olanzapine is a foundational treatment for schizophrenia, and long-acting injectables are foundational for the treatment of schizophrenia because there is so much relapse ongoing. When people relapse, they have a harder time getting back on track with functioning and potentially staying out of the hospital for long.

The issue with the previously available long-acting olanzapine formulation was the necessity of 3 hours of post-injection observation. This made it very difficult to use the medication because patients might have been against that, there weren't enough resources in the hospital, and emergency equipment needed to be available.

Formulating olanzapine for deep intramuscular injection in a way that avoided that post-injection observation period was really difficult until this new formulation became available.

Now, olanzapine can be given as a subcutaneous injection, into the subcutaneous fat, which may also help destigmatize long-acting injectable treatment and make it more widely available to patients without those previous administration barriers.

Patient Care Online: Your research has demonstrated how relapse can affect long-term outcomes in schizophrenia. How does that evidence underscore the importance of continuous antipsychotic treatment?

Correll: We know that, particularly at the beginning of treatment, patients respond quite well to antipsychotic treatment. But when they improve, experience side effects, or stop treatment, the risk of relapse increases significantly.

Every relapse has a biological, psychological, and social price that patients pay.

We know that with more relapses, there is a decrease in gray matter available in the brain. There is also self-stigma that ensues. People may begin to feel, "I am schizophrenic," rather than, "I have schizophrenia that I can deal with." They assume a chronic illness role.

We also know that there is more service utilization, emergency department visits, and hospitalizations. Unfortunately, there is something called secondary treatment resistance. Some people do not respond well to treatment from the beginning, but that proportion doubles to about 40% when we allow patients to relapse. There are processes in the brain that we haven't fully understood that make it harder for antipsychotics to take hold and for patients to respond after each relapse.

Acute efficacy is only the beginning of the journey, as with any chronic illness. We need to extend remission and symptom response into maintenance treatment to keep patients stable, but also allow them to take advantage of rehabilitation and social rehabilitation practices.

Symptom stability is only the beginning of the journey toward recovery, and relapses are the main enemies on the road to recovery.

Relapses are mostly related to nonadherence, and nonadherence is often not visible to us unless patients are receiving a long-acting injectable. Then we know whether they have returned for treatment.

If they do not return, there is still medication in the body, providing a window of opportunity for clinicians, family members, or caregivers to reach out and help bring patients back into care before treatment is completely interrupted.

Patient Care Online: The SOLARIS trial demonstrated improvements in PANSS, CGI-S, and PSP scores across all 3 dose strengths. Which findings stand out to you clinically, particularly regarding patients' functioning?

Correll: The SOLARIS trial was interesting because it included an 8-week acute treatment phase. Often, patients come into care when they are acutely ill, and with WELTRUZA, we can achieve therapeutic blood levels within a day or two without oral cotreatment, a booster injection 8 days later, a loading dose, or post-injection observation.

The improvement over those 8 weeks in total symptoms and global illness severity is a very good foundational step toward long-term care.

But patients are then discharged, and there is often a cliff after discharge. Many patients, up to 50%, actually stop their antipsychotic treatment.

The 8-week acute phase was followed by a 48-week open-label extension study. With more time, symptom improvement could also translate into functional improvement.

That was measured using the Personal and Social Performance (PSP) scale, which includes 4 domains: aggressive and uncooperative behavior, social interactions, leisure activities, and socially useful activities during the day.

The PSP score improved during the first 8 weeks and then improved further over the following 48 weeks, positioning patients beyond symptom improvement and toward functional improvement.

This is highly important because patients rarely come in and say they want to hear fewer voices or be less disorganized. They say, "I want to have friends. I want to go back to school. I don't want to have problems with my parents, and I want to be able to live independently."

That functional component is the ultimate goal when we treat patients. Therefore, maintenance stability and symptomatic stability are highly important to achieving that goal. With WELTRUZA, we saw both symptom improvement and functional improvement.

Patient Care Online: Weight gain and metabolic changes in SOLARIS were consistent with the known safety profile of oral olanzapine. How should clinicians balance efficacy against cardiometabolic risk when considering this treatment, and what monitoring is important?

Correll: This is an important conversation. We cannot just focus on efficacy. Every medication can also have side effects, and that includes olanzapine, whether it is given orally or as a long-acting injectable.

What we found with WELTRUZA was not a surprise. It had the same safety profile as other formulations of olanzapine. There can be constipation and sedation, but weight gain and metabolic abnormalities are among the more prominent side effects.

Despite that, olanzapine remains one of the most widely used and trusted medications. For many clinicians and patients, the risk-benefit balance seems to favor efficacy, but clearly, we need to monitor for weight gain.

There was further weight gain during the longer-term study. We need to monitor patients and help them develop healthier lifestyle behaviors, including eating more healthfully and exercising or at least moving for half an hour a day, ideally at least 3 times a week.

There are also medications that can mitigate antipsychotic-induced weight gain, including olanzapine-induced weight gain.

We have conducted several studies with metformin, which is an inexpensive and widely used medication for diabetes risk or diabetes itself, and which can also reduce weight gain. An even stronger signal has been observed with GLP-1 receptor agonist treatments. In some studies we have conducted, patients lost up to 9 kg, or almost 20 pounds, over 6 months.

That is certainly something patients should discuss with their health care professional to determine whether a medication like this could be beneficial.

In the 48-week study, weight gain was consistent with what we know from the history of oral olanzapine treatment over 1 year. There were not significant average changes in lipid or glucose abnormalities in this sample, which is encouraging.

However, we always need to monitor for these potential adverse effects with antipsychotics, particularly olanzapine.

Patient Care Online: WELTRUZA reaches therapeutic levels without oral cotreatment, loading doses, or booster injections. What does that mean for treatment initiation compared with other long-acting injectables?

Correll: This practicality is really important because we often need an acute and fast onset of long-acting injectable treatment, especially when it is initiated in an inpatient setting.

There is so much pressure on bed availability. Patients need to be stabilized initially but also discharged quickly to a lower level of care.

That can be achieved more easily when medications such as WELTRUZA, or another subcutaneous formulation such as risperidone (UZEDY), achieve therapeutic blood levels within a day or two.

If you do not need a booster injection 8 days later or overlap with oral treatment, where you do not know whether the patient is actually taking it, that simplifies initiation.

We want simple treatments, both from a health care provider perspective and from the patient's perspective, so patients do not have to think so much about their medication or have opportunities to miss doses and experience lower drug levels.

This simple approach—one injection followed by the next a month later, with maintenance levels of antipsychotic treatment in between—is a very nice addition to our armamentarium.

Patient Care Online: The intramuscular olanzapine LAI requires post-injection observation because of PDSS. Although WELTRUZA does not require monitoring, its label states that it is unknown whether PDSS can occur with subcutaneous administration. How should clinicians interpret this distinction and counsel patients?

Correll: PDSS stands for post-injection delirium/sedation syndrome. It can occur with the intramuscular olanzapine formulation that has been available since 2009.

During deep intramuscular injection, a blood vessel can potentially be damaged, allowing the medication to enter the bloodstream and dissolve rapidly. That can cause significant sedation and potentially impaired breathing, which is why 3 hours of post-injection observation is required, along with access to emergency intervention.

WELTRUZA was deliberately designed to avoid this risk.

First, it is injected subcutaneously rather than intramuscularly. Subcutaneous fat is much less vascularized, making it less likely that a blood vessel would be damaged and the medication released into the bloodstream.

Second, the formulation itself is different. It uses a copolymer that forms a depot and releases olanzapine slowly. Even in studies examining exposure to blood, the release was much slower than with the older intramuscular formulation.

The FDA obviously cannot say there is zero possibility for PDSS to occur because there have not been millions of injections administered yet. Therefore, the prescribing information needs to acknowledge that PDSS has been observed with the intramuscular formulation.

Clinicians need to know what PDSS is and be able to recognize it if it occurs.

However, there is no 3-hour post-injection observation requirement for WELTRUZA, and it does not have the PDSS-specific boxed warning associated with the older intramuscular formulation.

In nearly 4000 injections administered in the clinical development program at the time of our discussion, there had been no suspected or observed cases of PDSS.

Clinicians should put this into perspective: We need to be aware that this syndrome has occurred with another olanzapine formulation, but proactive 3-hour monitoring is not required with WELTRUZA.

Patient Care Online: Which patients are the clearest candidates for once-monthly subcutaneous olanzapine, and what should clinicians consider when discussing this option?

Correll: Whenever a new medication or formulation enters the market, the question for clinicians and patients is who might be the best candidate.

I think there are several good candidates.

The first group includes patients currently receiving oral olanzapine who benefit from the medication but may also benefit from assured long-term drug delivery.

We know that nonadherence is very common in schizophrenia. Even if it is not happening currently, it may happen in the future.

Patients receiving oral olanzapine should therefore be made aware that a long-acting injectable formulation now exists and can be administered without oral cotreatment, booster injections, or 3 hours of post-injection monitoring.

The second group includes patients who are receiving other long-acting injectables but remain suboptimally managed.

Olanzapine is often used in patients with more severe illness when other antipsychotics have not been sufficiently helpful. Previously, when these patients needed a long-acting injectable, there was not a practical olanzapine option without the previous monitoring requirements.

Clinicians should revisit how stable their patients are on first-generation long-acting injectables or risperidone, paliperidone, or aripiprazole LAIs and consider whether they might benefit from switching to olanzapine.

A third group includes patients who have not been started on either olanzapine or a long-acting injectable because there was no suitable long-acting olanzapine formulation available. They may now be able to initiate oral olanzapine and transition to the injectable formulation.

I think clinicians should discuss this option with patients through shared decision-making and involve family members and caregivers when appropriate.

We have found that the relatively low use of long-acting injectables—about 14% of schizophrenia prescriptions in the United States—is not necessarily because patients or caregivers refuse them. Sometimes health care professionals do not think about these options, do not offer them, or perceive them as too complicated to use.

Now, with a simpler way of initiating once-monthly injectable olanzapine, we have another opportunity to discuss long-acting injectable treatment more broadly and consider where olanzapine may fit.

Editor’s note: This summary was edited for the purposes of clarity using AI tools. Correll has disclosed serving as a consultant or advisor to, or receiving honoraria or research support from, AbbVie/Allergan, Alkermes, Bristol Myers Squibb/Karuna Therapeutics, Eli Lilly, Intra-Cellular Therapies, Janssen/Johnson & Johnson, Lundbeck, Otsuka, Sunovion, and Teva Pharmaceuticals.

References

1. Teva Pharmaceuticals. Teva announces U.S. Food and Drug Administration (FDA) approval of WELTRUZA (olanzapine) for extended-release injectable suspension, as the first and only once-monthly subcutaneous injectable olanzapine for adults with schizophrenia. Published October 9, 2026. https://www.tevapharm.com/news-and-media/latest-news/teva-announces.u.s.-food-and-drug-administration-fda-approval-of-weltruza-olanzapine-for-extended-re
2. WELTRUZA (olanzapine) for extended-release injectable suspension. Prescribing information. US Food and Drug Administration; 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/219007Orig1s000lbl.pdf