Current Role of Long-Acting Injectables in Bipolar 1 Disorder

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Vladimir Maletic, MD, MS, and Andrew Cutler, MD, share their insights into considerations surrounding the use of long-acting injectables in bipolar 1 disorder.

Vladimir Maletic, MD, MS: Andy, knowing everything you know, when would you suggest to our colleagues in the treatment algorithm—or are there any specific markers in our patients’ presentation—that would indicate we should consider using long-acting injectables [LAIs] earlier than people consider them now? When would you use them, and what markers indicate that long-acting injectables may be an appropriate choice?

Andrew Cutler, MD: Realistically, we’re probably not going to use them in the first line with the first mood episode. Although in the schizophrenia world, we are moving closer to that first line, or certainly very early in the illness phase. We’re probably talking about people who are demonstrating a significant vulnerability to relapse, either because of the underlying pathology, that they have a more brittle or serious form of the illness. You spoke to the heterogeneity; bipolar disorder is heterogeneous. It’s unfair to say there are only 2 types of bipolar, there are many types. Or due to the other issue we talked about, which is the adherence issue. Patients who are demonstrating that they are vulnerable to relapse with oral medications, either due to the illness itself or to their difficulty with adherence. That’s where it would rise to the top for me, and I would probably try to think about it as early as possible. Based on what we just talked about, I’m not going to let somebody have mood episode after mood episode and potentially be doing damage to the brain.

With LAIs you don’t have to feel like you’re closing the deal the first time you bring them up. You want to think about starting a conversation and say, “It appears it’s been hard for you to stay on the medication, and it seems like you’re having a lot of these episodes. And what happens when you have mania is that you end up in the hospital or jail, but maybe there’s a way here,” and bring the patient into the shared decision-making. “Maybe there’s another option here that could help you get where you want to go and to not have these things happening to you.” You start the conversation. We have a very good friend, Peter Weiden, he is a schizophrenia expert. He once said to me, “Andy, you offer them an LAI the first time, they’ll say no. You offer the second time, they say no. You offer it the third time, they say no. The fourth time they’ll say, ‘Why didn’t you tell me about this before?’” That’s how to think about it. Also, it depends on how you present it. You don’t say, “Would you like an injection? Do you want a shot of your medicine?” You say, “Are you interested in a modality that has been shown to prevent relapse and the consequences of relapse, and that you only have to take once a month, or only have to think about once a month? By the way, it’s delivered by a long-acting injection.” I’ve found I get better success that way.

Vladimir Maletic, MD, MS: On that note, you mentioned once a month. There is now a preparation that could be an every 2-month injection and may be comparable in efficacy to the aripiprazole option that is given only once a month.

Andrew Cutler, MD: Yes. The one that is on the market now is aripiprazole monohydrate. It’s indicated for once a month. But now there is a 2-month preparation of the same aripiprazole monohydrate. It has a higher amount of aripiprazole in the syringe that you’d be injecting. I have seen pharmacokinetic data for schizophrenia that show it maintains a therapeutic level for a full 2-month interval. By extension, it’s reasonable to think that it would also hold a charge for bipolar disorder for every 2 months. That would be a wonderful option because people with bipolar disorder, as I mentioned, are often higher functioning. It may be more inconvenient for them to take time off from work to come in more frequently, and it’s nice to be able to check in with patients through telemedicine. You don’t have to bring them in every month, you could do a monthly in-between injection telemedicine visit and check in with them. I think it’s a wonderful option for our patients.

Transcript edited for clarity

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