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Dr. Correll: 
Hello, my name is Christoph Correll. I'm Professor of Psychiatry at the Zucker School of Medicine at Hofstra Northwell in New York. Welcome to this program titled Too Soon is Not Soon Enough: Initiation of Long-Acting Injectable Antipsychotics, or LAIs, Sooner to Manage Symptoms of Suboptimally Treated Schizophrenia.

Schizophrenia is a severe disorder that is chronic and relapsing. So, relapse is the main enemy on the road to recovery; that is, symptomatic stability plus functional attainment. What do relapses due to patients’ lives? They enhance long-term symptoms and disability, they increase risk of suicide attempts, there's a progressive decline in gray matter brain structure, and a decrease in treatment response. After each relapse 1 in 6 patients may not respond as well anymore as they did before. And there's burden to patients, families, and caregivers.

In a treatment guideline, the TRRIP guideline to prevent and treat treatment resistance in schizophrenia, we recommended that at least one trial of an LAI should be given before we declare someone treatment resistant, because it might be pseudo resistant in many cases. One study showed that a third of treatment-resistant patients had subtherapeutic blood levels and a third of them had zero blood levels of antipsychotics.

Now, what is the evidence for LAIs? They actually work better than oral treatments to prevent relapse and hospitalization. That is proven in randomized trials, cohort studies, and even mirror image studies where patients serve as their own control, where you control the environment, their genetics, and the patient illness. Actually, a meta-analysis showed that LAIs together with clozapine were the most efficacious treatments to prevent mortality, or delay it both for all-cause, but also due to natural causes, and due to cardiovascular disease, as well as suicide.

We also know that when you give long-acting injectables early in the treatment course, during first-episode patients, their ability to reach recovery and functional attainment is vastly increased, more than 100% greater than when patients are treated with oral treatments from the beginning.

We did a study looking at different initiation strategies with long-acting injectables, either proactive, you give it before patients are nonadherent, before they have a sign of relapse. Or you wait for the relapse, or you wait for multiple relapses. And the earlier the treatment is given, the better the outcome, preventing number of inpatient admissions, the number of days spent in the hospital, number of emergency room visits.

These were data from the U.S., but they were also replicated in a study in Hong Kong, where basically LAIs beat oral treatments against all-cause emergency department visits, hospitalizations, hospitalization for psychiatric disorders or schizophrenia, and even incident suicide attempt. But within the LAI use, when it was given within the first 2 years, the protective effect was even larger. So, a stitch in time saves 9, and using LAIs early in the treatment algorithm can help patients have better outcomes.

This was actually recognized as a relevant treatment recommendation by the Florida guidelines where patients who are first-episode patients and respond and do well on an oral treatment and even when they're currently adherent to the oral treatment, have level evidence A to continue on the oral treatment and frankly wait for nonadherence to creep in, or right away go into long-acting treatment options so that they can prevent or make visible nonadherence in the future, reducing the trigger points of should I or should I not take the treatment from 365 times a year to maybe 12 or 6 or even 4 or 2 times a year.

So acute and long-term goals need to be combined in the treatment that is effective for schizophrenia, maintenance therapy for relapse prevention is a critical goal, risks and benefits need to be optimized and balanced, and high-risk groups for relapse and breakthrough psychosis require extra attention, but using LATs, long-acting treatments, more often and early in the illness course is key to reduce treatment discontinuation, relapse, hospitalization risks, premature mortality, and improve functioning.

Thank you for your attention.

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