In an interview with Pharmacy Times, Roger Rivera, DNP, PMHNP, an educator and doctorally trained psychiatric nurse practitioner and family nurse practitioner (FNP) who practices in community clinics in Kissimmee, Florida, and Alberto Augsten, PharmD, MS, BCPP, DABAT, a clinical pharmacy manager at Memorial Regional Hospital in South Florida, discussed the expanding use of glucagon-like peptide-1 (GLP-1) receptor agonists in patients with serious mental illness (SMI), a population carrying substantial antipsychotic-associated metabolic burden.
Augsten explained that GLP-1s act outside the receptor pathways antipsychotics target, allowing metabolic benefit without antagonizing psychiatric efficacy—though slowed gastrointestinal transit time may alter the peak and maximum concentration of co-administered medications. Rivera emphasized confirming psychiatric stability before initiation, cautioning against destabilizing patients who have only recently gotten well. Both identified pharmacists as an underused early warning system for emerging psychiatric and pharmacologic complications.
The Rationale: Treating Metabolic Burden Without Trading Away Psychiatric Stability
Pharmacy Times: Antipsychotic-associated weight gain has long been a barrier in SMI care. What makes GLP-1 receptor agonists a compelling option, and how should clinicians think about the brain-versus-body trade-off?
Alberto Augsten, PharmD, MS, BCPP, DABAT: It's been long known that antipsychotics have a propensity to result in what's called metabolic syndrome. It's not just an increase in weight gain; it's an increase in their lipid profiles—whether it's their low-density lipoprotein rising, triglycerides rising, or general cholesterol. We also see changes in insulin resistance, so they can have elevations in something called their hemoglobin A1c. It's something that actually mimics folks who have diabetes.
The mechanism of GLP-1s is completely outside of [the antipsychotic's] primary locations, meaning it's not directly antagonizing what the antipsychotic does—which is a positive thing. The last thing you want to do is antagonize what's intended to happen from the primary agent. It's still going to work to treat folks with schizophrenia and folks with bipolar disorder—and yet the GLP-1 can enter and do its job and help reduce weight and reduce the metabolic burden that occurs with antipsychotics.
Roger Rivera, DNP, PMHNP: The core concept here would be that psychiatric recovery and metabolic recovery should not compete against each other. For years in psychiatry, we were sometimes forced to have a painful trade-off: mental stability versus metabolic health. Ideally, in the future, it's not choosing between the brain and the body. Now it's, let's choose something that off the bat I could continue using without having to go into this metabolic compromise. A patient losing weight but relapsing psychiatrically is not really a successful outcome.
Before You Initiate: Patient Selection Meets Pharmacokinetics
Pharmacy Times: Before starting a GLP-1 in a patient with SMI, what should the care team assess—both clinically and pharmacologically?
Key Takeaways
1. Stability comes before metabolic intervention. Before initiating a GLP-1, the care team should assess recent hospitalizations, time since the last mood or psychotic episode, medication adherence history, and regimen complexity.
2. Slowed transit time is the central pharmacokinetic concern. Because GLP-1s delay gastric emptying, the time to peak and maximum concentration of co-administered psychotropics may shift.
3. Pharmacists catch destabilization first—and set expectations. Community pharmacists often see these patients multiple times weekly and can flag sedation changes, appetite shifts, insomnia, or activation before a psychiatric crisis develops.
Rivera: Honestly, the biggest takeaway here is going to be stability first. Don't destabilize someone who just got well or someone that's been well for a while. In the context of stability and recent hospitalizations, we want to look at when the last time we had mania was. When's the last time we had any of these prevailing episodes? Has there been an issue with medication non-adherence? Not every stable patient is truly stable. Sometimes stability is recent, it's fragile, or it's heavily medication-dependent, so those changes have to be very minute and very individualized to that person. The other thing you want to look at is regimen complexity—how long did it take us to get stable?
Augsten: One of the ways we like to educate, to keep it simple, is it slows everything down. The term we like to use in pharmacotherapy for that is that it slows transit time. The most interesting complication that can happen with any of these GLP-1s is that the time for the medication we normally take—whichever one it is—to reach its peak, or the time to reach its maximum concentration, may now be altered. To be quite honest, there are only a few studies that have identified what this really looks like in most patients, so there's not enough information at this point in time to know exactly what we may expect. The most important advice one could give is to just be aware that whatever we're taking, there may be changes to when it peaks.
The Pharmacist As An Early-Warning System
Pharmacy Times: Once a GLP-1 is initiated, what role does the pharmacist play in catching early problems—both psychiatric and pharmacologic?
Rivera: This is where pharmacists are often the most underutilized early-warning system in mental health care. The pharmacist is going to be aware of nausea, vomiting, sedation changes, and appetite shifts, which are going to play a significant role in the psychiatric component. They're always going to be giving patients key signs of destabilization, not just explaining it to them but also observing for the insomnia and the activation. A pharmacist may notice the beginning of destabilization way before it becomes a psychiatric crisis—a lot of times they'll see that client a couple of times during the week picking up their medication. A lot of times I reach out to them first, right before I make some of these decisions.
Augsten: Any medication that affects the gastrointestinal tract is something I have to have more eyes on. For example, there's an antipsychotic known as clozapine, which is an excellent antipsychotic. Unfortunately, it can cause severe constipation, and that's one of the things we monitor for. So you can imagine that if you have two medications that are both slowing down the transit time, that could be something I need to keep close eyes on. There are medications that we monitor based on their blood levels—do they have a peak that goes really high or a trough that goes very low? The most important thing to do when those interactions arise is to continue to monitor those blood levels more closely until we know what the stabilization looks like.
Purposeful Prescribing: Expectations, Adherence, And The Long Game
Pharmacy Times: As GLP-1 use expands, how should clinicians and pharmacists frame expectations given these agents don’t treat the underlying psychiatric disease?
Augsten: Adherence is an issue, and there are a lot of studies that tie adherence to outcome. If we tie it to a positive outcome—and if the conversation is a positive conversation with motivational interviewing—these patients are more likely to take those medications, and they build trust. But expectations matter. People are hearing fantastic stories, so everybody goes into this thinking, oh, I'm going to lose 30, 40, 50 pounds. In the earlier studies, on average, 10% weight loss was a good goal. The bottom line is this is not treating my underlying psychiatric disorder; it's treating what's going on from a metabolic and weight component. If we can tie the initiation of this to behavioral changes—changes in diet, changes in exercise—we may have lifelong changes for these patients.
Rivera: It means treating the human being, not chasing a number on a scale. Gradual titration is imperative—not everybody is going to react the same on the same dosages. That's the whole adage of starting low and going slow. The other thing we want to do is make a treatment plan for all our individuals: a game plan. What is our goal? Then back to the pillars of life, too: the physical activity; the nutritional intake, not just the chemical component; and then, of course, the sleep. So, realistic expectations. Everybody's mental health journey is different, so we preserve that psychiatric continuity, but in a balanced manner, because we have to reduce the barriers so patients can access that treatment safely.
