John M. Kane, MD: So back to that question about why they are so underutilized. I guess we’ve raised some of the issues. Some of it is maybe the hassle that clinicians might feel. There’s perhaps some patient resistance. You said that if a patient is adamantly refusing medication, they’re probably not going to get the injections either. But I think for many patients, it’s more of an issue in the way the clinical team is communicating this, and the ambivalence, perhaps, that people have. We talked about some of the, I guess, concerns about how medications are necessary or not, and are we overusing them? I think that once the clinical team gets to the point where they say, “This patient should be on medication,” then it should be relatively straightforward to say, “Well, why not use a long-acting injectable [LAI] formulation?” I think there is still this fear that we’re being too maternalistic or too evasive if we give someone an injection.
Jeffrey A. Lieberman, MD: Definitely. But there’s actually something that’s even more, I don’t know, potentially problematic than that. People who are candidates for LAIs are usually SMI patients. They have some serious mental illness. And serious mental illness patients are usually on Medicaid, or of lower SES [socioeconomic status], and are getting treated in clinics. And the clinics are often run by nonphysicians. And there is maybe sort of a discipline or an ideological sort of orientation that is not facilitating optimal usage of these more complicated treatments.
T. Scott Stroup, MD, MPH: I think that all may be true. I think we also are trying to respect patient preference, though. So I think doctors shouldn’t be the barrier. Doctors should recommend it and make sure there are no structural problems we could ideally do away with, such as health system issues. But if patients really have a preference for oral medications, it’s kind of hard to override that.
Jeffrey A. Lieberman, MD: But if they want oral medications, they have to take them, right?
John M. Kane, MD: Well, I think the challenge is no one wants an injection, right? If you say to somebody, “How about we give you injections instead of pills,” most are going to say, “No, I don’t want that.” So they have to understand what the issues are. And I think my response is, “Look, we’ve treated many, many people like you. What we find is that anybody with a chronic illness, whether it’s diabetes or hypertension or schizophrenia, has trouble taking their medicine for lots of different reasons. Why should we take a chance on that? Why should we take a chance on you getting sick again, ending up back in the hospital, losing all the gains that you’ve worked so hard to achieve? Let’s do something that’s going to really facilitate that.”
Jeffrey A. Lieberman, MD: How often do you think that doctors have that kind of a conversation?
John M. Kane, MD: I think that’s where we fall short.
Jeffrey A. Lieberman, MD: They need to be taught that way early.
John M. Kane, MD: We need to teach doctors how to have that conversation.
T. Scott Stroup, MD, MPH: Right, to use their experience and knowledge and their powers of persuasion. I mean, that’s what you’re talking about.
John M. Kane, MD: And it’s part of the therapeutic alliance. Some doctors say, “It’s going to interfere with the therapeutic alliance if I recommend an injection because that means I don’t trust you.” We’re trying to capitalize on all our past experience and all the data that enable us to try to help that patient avoid what some others have experienced.
Jeffrey A. Lieberman, MD: Right. It’s a superior form, in [terms of] the medication we’ve had. Let me ask you a question though, John, speaking of the LAI second-generation drugs. Scott did some pioneering regarding the comparative effectiveness of first- and second-generation long-acting injectable medicines. Olanzapine is kind of out of the picture, just because of postinjection delirium and sedation, or something like that?
T. Scott Stroup, MD, MPH: That’s right. Syndrome.
Jeffrey A. Lieberman, MD: Yeah, is that it? So it’s got a bad mark, I guess.
John M. Kane, MD: It’s a rare effect, but it does happen, and it means that patients need to be observed for a couple of hours after the injection. For some people it’s still a very valuable drug.
T. Scott Stroup, MD, MPH: It is?
John M. Kane, MD: It is being used, yes.
Jeffrey A. Lieberman, MD: It is valuable, but it’s being avoided like the plague because of the fact of this rare effect. But Invega Sustenna, or paliperidone palmitate, or whatever, olanzapine pamoate, or whatever version of it you want to use, versus aripiprazole: that would be an interesting study. That would be an interesting study to see.
John M. Kane, MD: Well, there have been some studies, but I think the question, again, is making a personalized decision for each patient when trying to decide what’s the best medicine. We do that with oral medicines all the time, right?
Jeffrey A. Lieberman, MD: Wouldn’t it be nice to have data to base that decision on?
John M. Kane, MD: Sure.
Jeffrey A. Lieberman, MD: Do you have any predictions on how that would pan out?
John M. Kane, MD: I think the studies comparing paliperidone palmitate or risperidone with aripiprazole have shown that they’re pretty similar, except in terms of adverse effects.
People worry sometimes that 1 drug is more efficacious than another. But I think, in general, against positive symptoms, the antipsychotic drugs have been similar in their effects, except for clozapine.
Jeffrey A. Lieberman, MD: That’s what Scott’s study showed. If the difference between Invega Sustenna and aripiprazole, in whatever formulation it’s compared with, or both, then the question is, what are the adverse-effect differences that would emerge from that, assuming the efficacy would be comparable?
John M. Kane, MD: Yeah, and which patients are vulnerable to which specific adverse effects? And some day, hopefully we’ll be better able to predict that.
T. Scott Stroup, MD, MPH: And who will benefit from the 2 weeks, 4 weeks, 6 weeks, or whatever the upper limit is now?
John M. Kane, MD: Right, absolutely.