LAI Antipsychotics in Schizophrenia: Tolerability

Experts in the management of patients with schizophrenia comment on the safety profiles of long-acting injectable therapies versus oral agents for the treatment of schizophrenia.

John M. Kane, MD: So 1 of the questions that comes up with LAIs [long-acting injectables] is patients say, “Well, can I stop it?” And I think the answer is, “Yes, you can stop it. You can’t stop it tomorrow, but you can stop it a month from now or 2 months from now.” But then the next question is, “What if I develop an adverse effect? Am I going to be able to deal with that adverse effect because I’m still on the drug?” And this is something that we’ve looked at pretty carefully. I think neuroleptic malignant syndrome would probably be 1 of the most concerning adverse effects. It’s extremely rare among patients getting long-acting formulations, and there’s no evidence from the cases that have developed that the outcome is any worse if someone’s receiving injectable medicine as compared with oral medicine.

In general, these medicines are pretty well tolerated. We talk about metabolic adverse effects and some neurologic adverse effects. But in terms of life-threatening conditions, they’re pretty well tolerated. So I think that’s a little bit of a red herring—to say, “I can’t stop the drug.” And you mentioned earlier, the 3-monthly formulation of paliperidone. That was a question that I think initially came out. People were saying, “Well, that’s a very long interval.”

The way that medication is used is that no one is going to have the 3-month interval until they’ve been on the once-monthly interval for 4 months. So you have a chance to see whether someone is tolerating the drug well and can assess how they’re doing. And then you can introduce the every-3-month option. Eventually I hope there’s going to be an every-6-month option.

And if you think about somebody who’s maybe a little ambivalent about taking medication, and you realize you have to get an injection only 4 times a year, then that’s a situation in which maybe your relatives, or friends, significant others, whatever, can maybe help you kind of make sure that you’re taking advantage of that opportunity.

T. Scott Stroup, MD, MPH: I kind of worry with the idea that you’re supposed to take the 1-month option for 4 months before you switch over. Do you think people really wait?

John M. Kane, MD: I actually have not seen a few studies to see how it’s being used.

T. Scott Stroup, MD, MPH: Yeah, I worry that people might jump the gun.

John M. Kane, MD: They might. But I always tell people to try to follow the package insert. There’s a reason why it’s there.

T. Scott Stroup, MD, MPH: Good idea.

John M. Kane, MD: And also, are you so eager that you need to switch to the 3-month option that you couldn’t wait another month? I don’t know.

T. Scott Stroup, MD, MPH: I wanted to go back to something you said a minute ago, just before I forget. Just about the idea of peaks and troughs of the oral versus long-acting medications. I actually didn’t know anyone had actually looked at the adverse effects between long-acting injectables and oral medications. I found the meta-analysis that you were involved with. And I was somewhat surprised to find that you really didn’t find adverse-effect differences between oral and long-acting medications.

John M. Kane, MD: That was very interesting.

Jeffrey A. Lieberman, MD: Well, it cuts both ways. A long-acting medication didn’t have more adverse effects than oral, but the expected finding was that maybe an oral would be worse because of the fact that you have these peak concentrations. Lessons also borne out.

I don’t see any negatives, other than the injection and whatever the additional effort needed is with the long-acting formulation. It seems to me that to have this mode of administration with constant bioavailability is a potential advantage. I would really be interested in seeing head-to-head efficacy studies on this. I remember there was an article that Solomon Snyder and Larry Tune wrote—this is dating us, John—many years ago, that looked at the pharmacodynamic effects of fluphenazine administered by oral and decanoate forms. I forget exactly what the variables they were measuring, but they suggested that it was a more efficient therapeutic mode of action.