LAIs in Schizophrenia: Shortcomings in Available Guidelines

Peter L. Salgo, MD: You say these injectables have been out for a while.

John M. Kane, MD: Yes.

Peter L. Salgo, MD: I know there are guidelines for them. I’ve got a list of them over here. Why don’t we run down the guidelines and see where we are. There’s an AACP [American Association of Colleges of Pharmacy] guideline. What does that say?

John M. Kane, MD: I think we need to start with that in my opinion, the guidelines have been very slow to catch up with the data. But the AACP guidelines suggest that patients should receive oral medicine initially. They should be given a trial. If the medicine fails, then they could be given a trial of another oral medicine. But if that fails, they really should get a trial of a long-acting formulation. If there’s any evidence that nonadherence is involved or the person is having difficulty taking their oral medicine, then a long-acting formulation should be used.

Peter L. Salgo, MD: But what I heard first is the AACP guidelines start with oral medicines. Don’t go directly….

John M. Kane, MD: Most people will say start with oral medicines because you want to be able to titrate the dose very quickly when you’re starting someone on new medicine. You want to make sure that they react well to it, that they don’t have any adverse effects. Once you do that, then you can switch to a long-acting formulation.

Peter L. Salgo, MD: It’s interesting. When you’re beginning treatment and you’re titrating treatment, the objectives are different than once you’ve reached chronic therapy.

John M. Kane, MD: Yes.

Peter L. Salgo, MD: Early on you want short half-life, the ability to titrate, and then longer, you don’t want a short half-life—you want this dose to plateau.

John M. Kane, MD: Right. In all honesty, you actually could treat an acutely ill patient with a long-acting formulation. We’re not there yet in terms of implementation in clinical practice, but I think some day we might be. Right now, I would be satisfied if people start on an oral medicine, give the patient a little time, understand their reaction, and understand their adverse effects, but introduce the concept of a long-acting formulation very early in the discussion.

Peter L. Salgo, MD: What about the NCBH [National Council for Behavioral Health] guidelines, what do they say?

John M. Kane, MD: The National Council for Behavioral Health is also suggesting that long-acting formulations are underutilized. They emphasize that the conversation should begin early in the process, that we shouldn’t wait until people have had multiple relapses due to nonadherence, and that clinicians should engage the patient in a discussion that might include motivational interviewing. There should be shared decision making, and all of these things. But the emphasis is on doing that sooner rather than later.

Peter L. Salgo, MD: I was surprised that there are specific state guidelines—Florida Medicaid guidelines—and these actually include recommendations for formularies and for practitioners to implement LAIs [long-acting injectables]. Where does that fit in the cosmic scheme of all of this?

John M. Kane, MD: It’s very similar to what we were saying about emphasizing earlier use and emphasizing not waiting until someone has had multiple relapses before considering a long-acting formulation.

Peter L. Salgo, MD: Are there other states adopting the Florida guidelines?

John M. Kane, MD: Actually, I’m not aware of other states. I think the guidelines that people are waiting for are the new American Psychiatric Association [APA] guidelines.

Peter L. Salgo, MD: I was coming to that.

John M. Kane, MD: The last guidelines that the APA published were in 2004, so it’s been a long time.

Peter L. Salgo, MD: Can I just pause you there? Because you wondered why there was such a slow adoption rate among clinicians for anything new. Here’s the APA in possession of LAI information for 15 years, right?

John M. Kane, MD: Right.

Peter L. Salgo, MD: Now they’re adopting new guidelines. They’re out for review.

John M. Kane, MD: They’re out for review, but the first draft was still a little disappointing, in all honesty. I think they’ve been very conservative, and the last guidelines they issued suggested that long-acting formulations should be considered in patients who’ve had multiple relapses due to nonadherence. In my opinion, you don’t want to have multiple relapses no matter what they’re due to—you want to try to avoid that from the get-go. The data suggest that more than half of our patients are going to have trouble taking medicine regularly orally. If we know that more than half of our patients are going to have trouble taking medicine and we can’t identify which patient, why wouldn’t we use a long-acting formulation in everybody?

Peter L. Salgo, MD: I keep coming back and anchoring this as a physiologic disease and comparing it to others. There are lots of diseases in which there are newer, better formulations, and yet the recommendations are always to ramp up from what we already know to the newer formulations, even if we are aware that what we know doesn’t work very well.

John M. Kane, MD: No.

Peter L. Salgo, MD: It’s not just psychiatry, and it’s not just schizophrenia. But it’s wrong for that disease. It seems to be wrong for schizophrenia, too.

John M. Kane, MD: But I also think the irony is there are many diseases in medicine where it’s clearly known that people have trouble taking medicine. If clinicians had a long-acting formulation that they could offer to patients, they would be all over it.

Peter L. Salgo, MD: Do you follow any published guidelines?

John M. Kane, MD: I’d like to think I’m a little ahead of the guidelines, if I can say that. But I think the problem with the guidelines is it can take a while to catch up with the evidence. I think there’s a sense some people have that if we recommend long-acting formulations, we’re somehow taking away the person’s autonomy.

Peter L. Salgo, MD: Which person’s autonomy, the clinician’s or the patient’s?

John M. Kane, MD: The patient’s autonomy. In the United States we’re very concerned about individual freedom, autonomy, and things like that. But in my opinion, if you have a brain disease like schizophrenia or Alzheimer disease, we also need to recognize that we’re in a position to really help that person manage his or her illness in a more effective way.

Peter L. Salgo, MD: Two things occur to me hearing that. First, there’s nothing in a guideline that is restrictive, which says you must do this. This is something what we recommend. Second, where’s the autonomy really? If you came in with pneumococcal pneumonia, does the patient have the autonomy to take saline as opposed to penicillin? Probably not.

John M. Kane, MD: No, you’re right. In my opinion, this is a misperception. I think we’re not trying to control the patient. We’re trying to control the patient’s illness, and we’re trying to work with the patient to help them control their illness. Once we’ve made a decision as to the diagnosis and the appropriateness of medication, then why wouldn’t we deliver that medication in a way that’s more guaranteed, if you will. Why not? The question people might say is, “Well, do the long-acting formulations have more adverse effects?” They don’t. There’s absolutely no evidence that they have more adverse effects, assuming of course that someone’s taking the oral medicine.

Transcript edited for clarity.