Underutilization of LAI Antipsychotics in Schizophrenia

John M. Kane, MD: Let’s talk a little bit about the difference between oral medications and long-acting injectable [LAI] formulations. We’ve had long-acting injectable formulations for several decades, and they’re still underutilized. I think it’s something we can talk about—the extent to which we think they’re underutilized—but that’s certainly my impression. And perhaps one of the challenges has been that the data, at times, have been confusing. We look at the randomized controlled trials comparing long-acting and oral medications, and they’re not always consistently showing an advantage for the long-acting injectables. The most recent meta-analysis of ours did not show a consistent advantage for the LAIs.

But if you look at the mirror-image studies, the results are pretty compelling. The long-acting injectables are superior, if you look at the cohort studies, or the kind of naturalistic studies that have been done. And we published a meta-analysis last year in the Schizophrenia Bulletin looking at 42 of the cohort studies, and we did see a significant advantage for the long-acting injectable drugs, in terms of rate of hospitalization and all-cause discontinuation. So I think part of it is, how do we go about studying this? And how do we translate those data into communications to physicians at large, and families, and patients?

My own personal impression is that there are enormous advantages to the long-acting injectable medicines. As we mentioned before, just the idea that you know for sure whether someone is taking their medicine. If someone does have a relapse, you know that they’ve broken through despite taking medicine. If someone relapses on oral medicine, half the time we’re not sure if they’ve been taking it. And when someone comes to an emergency department, we don’t usually do a blood level to find out if they’ve actually got the drug in their system.

So I think there are a lot of clear advantages to the long-acting injectable formulations, but we still have a long way to go in terms of getting universal buy-in as to what those advantages might be.

Jeffrey A. Lieberman, MD: John, how much do you think that the underuse of long-acting injectables is related to the aversion to giving injections by a psychiatrist?

John M. Kane, MD: I think that may be part of it. I don’t think that’s the biggest part of it because it’s not always the physician who is giving the injections. It often is a nurse or a nurse practitioner. And, yes, there are many hospitals that have those personnel who are available to give injections. In some states, pharmacists can give injections. So I think it’s more along the lines of, what prevents doctors from even thinking about this as an option? And we’ll come back to that a little later in the discussion.

When we think about oral medications, we’ve talked about some of the challenges. But when we talk about long-acting injectable formulations, do you think patients have as much of a challenge in terms of continuing on them as they do when continuing on oral medication?

T. Scott Stroup, MD, MPH: For people who really don’t want to take medications, in the absence of some compulsion to take them, they’re not going to take either kind.

John M. Kane, MD: Do you think there’s any promise to using a behavioral economic strategy, that people could be incentivized for taking medicine? There’ve been a couple of studies in Europe suggesting that might be feasible.

T. Scott Stroup, MD, MPH: This is a contingency management that you get paid to come and get your shot?

John M. Kane, MD: Yes.

T. Scott Stroup, MD, MPH: I think that’s very promising. I think in the substance use world that these contingency management setups are helping people stop using cocaine, and cigarette smoking, too.

John M. Kane, MD: Yes. Jeffrey, you had asked what the obstacles are. Is it really that the doctors don’t want to have to give the injections themselves? I think for some people that might be the case, but I think the bigger issue is that physicians are not necessarily comfortable with or adept at having the conversation with the patient that would introduce the topic and help the patient, through shared decision-making, recognize that this is a very good alternative for managing their illness.

I think many people have assumed it’s the patients who are objecting to the injections, but I think a lot of research now has shown that it’s more of a problem in terms of the clinical team not really providing the input. Surveys that have been done have suggested that doctors say, “Well, I suggested it to my patient, but he said no.” But then when the patient is asked, the patient says, “Well, actually no one ever really explained that to me.” So I think that’s part of our challenge—getting the message out that this is a very viable way to treat patients.

T. Scott Stroup, MD, MPH: I think it’s analogous to clozapine in some ways.

John M. Kane, MD: Yes, very much so.

T. Scott Stroup, MD, MPH: Doctors think that patients won’t want it or don’t want to do it. And then the flip side of that is, it’s more of a hassle for the doctor. So there’s this, “I don’t think the patients want it. It’s kind of a hassle for me, so I don’t ever bring it up.” And I think that is one way, if we could change doctors’ behaviors a little bit. And I think Jeff’s right. Actually, I do think that it is a little bit of a barrier—that doctors don’t know how to give shots, or won’t give shots. If you have a nurse who can give the shots, great. But otherwise, you’ve got to know how to do it and be willing to do it.

John M. Kane, MD: That’s true. But maybe we shouldn’t be relying on the doctors to give injections. Is it necessary to have an MD give an injection? We’re all very pressed for time, so maybe we need to understand how to better use pharmacists, and nurses, and….

T. Scott Stroup, MD, MPH: If there are alternatives, that’s great. But if there are no alternatives, then they won’t get it.

John M. Kane, MD: Well, that becomes another challenge for the system, so to speak.

Transcript edited for clarity.