Improving Resistance to Use LAI Therapy in Schizophrenia

John M. Kane, MD: So I think before we even get to choosing which one, we sort of want to get people to at least consider the possibility of using an LAI [long-acting injectable]. And the fact that they have so many different options now should make it somewhat easier. You know 1 of the questions is also, “How early would you propose the use of LAIs?” And we’ve mentioned earlier that some of the guidelines suggest you should wait until someone has demonstrated nonadherence repeatedly. My view is that you really want to prevent as many relapses as you can from the get-go.

So when we’re asked, “Would you use an LAI in a first-episode patient,” I would say yes, because we really don’t want that person to relapse. We know that the extent to which you can get the illness under control in the first couple of years is a very powerful prognostic indicator. So I really want to do everything I can to prevent that first relapse. And we go back to the data that we cited earlier, that with each relapse the response may be less good than it was the last time. We may be on a pathway to treatment resistance. So we want to avoid all those things.

And when I think about 1 of the first-episode patients who we treat, who do really well following their acute hospitalization—they go back to school or back to work, and they feel great, and everything’s fine—those are the people who often want to stop their meds and often get into real difficulty and lose a lot of the gains that they’ve made. I think if we can offer them injections from the get-go and make it easier, so they don’t have to take pills in front of their roommate and can just go to a clinic or to a doctor and get an injection once in a while, I think it can make things much more comfortable.

We’ve actually recently done a study with several hundred first-episode and early-phase patients, and we got about 86% to agree to injections. But the way that was done was going out to the clinical teams and training them on how to have a conversation with the patient. First educating them about the whole concept and how to use these drugs. But the key thing was, how do I talk to them? What do I do when the patient says, “No, I don’t like needles” or “No, I don’t want an injection”? You don’t just give up. It’s a conversation. And Peter Weiden published an interesting paper in the Journal of Clinical Psychiatry a few years ago regarding a study in which they recorded the conversations between doctors and patients about LAIs.

It was almost comical, some of the things that people say even though they knew that they were being recorded. We take for granted a lot of our ability to have conversations with patients, but I think it requires training. It’s not something that just comes naturally.

T. Scott Stroup, MD, MPH: Was there some sort of script? A specific phrase that helped?

John M. Kane, MD: There was also role playing. We sat with the doctors and we said, “OK, what would you say? I’m the patient, and I’m saying, ‘No, I don’t want to do this.’ What are you going to say?” And I was trying to give him as hard of a time as I could, to get him comfortable really having this conversation—not in a pejorative way, but let’s try to be really constructive.

Jeffrey A. Lieberman, MD: What about nurse practitioners?

John M. Kane, MD: I think it’s the same thing. To me, the other thing that was important in this project was the whole clinical team. If I’m a patient, and my therapist is a social worker who thinks that injections are terrible, he or she may undermine the whole thing. So that person also has to be on board.

T. Scott Stroup, MD, MPH: I think that’s smart, and you were sort of alluding to that earlier, Jeff. If the social work team is anti-shots, then it’s a problem.

John M. Kane, MD: Yeah. And some of the studies that have been done recently suggest that patients have a much closer relationship with their therapist than they do with their prescriber. So that person needs to be supportive of the whole thing. And then families. I think families can be very important advocates for this. If you have a loved one who has had a psychotic relapse and has lost insight, and you have to call the police to take that person to a hospital and have them hospitalized against their will, what a traumatic experience for everybody. So when that person is discharged from the hospital, it wouldn’t be surprising for the family to be reminding them to take their medicine or to be concerned about whether they’re taking the medicine. If you have long-acting injectable formulations in the picture, you’ve eliminated that family tension, which I think can go a long way. So I’d say families are important. Also, what about peer counselors? I don’t know if you guys have had experience with peer counselors, but many people feel that if you have someone with lived experience, they can communicate more effectively with patients.

Jeffrey A. Lieberman, MD: Absolutely.

T. Scott Stroup, MD, MPH: I think it’s a great idea. I know that some peer counselors or people who train peer counselors have been concerned that they feel like they’re being co-opted by the system if they’re sort of on the take-meds team. I don’t have a problem with that, but I’ve heard that’s an issue.

Jeffrey A. Lieberman, MD: Do you think that if there were oral long-acting medications there would be less resistance to using them?

John M. Kane, MD: I think that would be a nice addition to the alternative options. We did an experiment a long time ago with a once-weekly oral that never made it to market, and it worked quite well. So I think, yes, that would be a nice option to have.

Jeffrey A. Lieberman, MD: This is penfluridol?

John M. Kane, MD: That was penfluridol, yes—diphenylbutylpiperidine. But some of the current drugs have long half-lives, so they could conceivably be given less than every day. I think some people worry that, “If I’m taking an oral medicine once a week and now I miss that, then I’m really in trouble.” But you could have that supervised. I think to me, the more options we have, the better. You have a better chance of finding something that’s going to work for that particular patient.

Jeffrey A. Lieberman, MD: Well, if injections are a deterrent for whatever reasons, then I suppose implants are going to be even more objectionable.

John M. Kane, MD: Yeah, but people have experimented with that. It’s certainly feasible to have implants.

T. Scott Stroup, MD, MPH: Are there some in development, still?

John M. Kane, MD: You know, I’ve lost track of what happened with that.

T. Scott Stroup, MD, MPH: One more thing about long-acting injectables, in terms of whom to recommend them for. What about people who smoke marijuana?

John M. Kane, MD: Personally, if I have someone who’s smoking a lot of marijuana, I would be more comfortable if they’re also getting a long-acting injection. Then I know they’re not going to stop their medicine on Saturday because they say I want to get stoned tonight. I would sleep better at night knowing that they’re on an injectable medicine.

Jeffrey A. Lieberman, MD: Is there a second- or third-generation antipsychotic that you would like to see an LAI developed for?

John M. Kane, MD: It would be great if we had 1 for clozapine, right? It’s a question of formulation. Some medicines don’t lend themselves to long-acting formulations.

Jeffrey A. Lieberman, MD: I think the fact that we have Invega, which is paliperidone, and aripiprazole, represents a good sort of spectrum. I mean, it would be nice if olanzapine wasn’t troubled by this, but it shouldn’t be an absolute deterrent.

Transcript edited for clarity.