Managing Agitation in Schizophrenia and Bipolar Disorder

For patients with schizophrenia and bipolar disorder who exhibit agitation, suboptimal treatments have been overused while better-tolerated and possibly more-effective interventions have been underused, according to findings reported at Psych Congress, held virtually and in San Antonio.

In this first of four exclusive episodes, MedPage Today brought together three expert leaders in the field -- moderator Leslie Citrome, MD, of New York Medical College in Valhalla, is joined by John Kane, MD, of Northwell Health in Long Island, New York, and Jonathan Meyer, MD, of the University of California San Diego -- for a virtual roundtable discussion about what's new, what's available, and what's next for treating agitation in schizophrenia and bipolar disorder.

Following is a transcript of their remarks:

Citrome: Hello, and welcome to our Psych Congress video roundtable. We'll be talking about hot issues in schizophrenia. Joining me today are doctors John Kane and Jonathan Meyer. Welcome.

Kane: Thanks very much.

Meyer: Thanks for having me, Les, really appreciate it.

Citrome: Let's talk about managing agitation in schizophrenia and bipolar disorder. What's available, what's new and what's next. Well, there's a lot of new information that's been gathered over the past 5, 10 years, about what we mean by agitation. And new agents have been developed to address agitation. Gone are the days of ultimate reliance on haloperidol in combination with lorazepam, the B-52. Although still in common use, we do have now new alternatives that are better tolerated and perhaps even more efficacious. Underutilized are intramuscular ziprasidone and intramuscular olanzapine in fast-acting intramuscular formulations. They've been studied in the populations that we treat every day.

In a presentation that was given, we heard that ziprasidone IM [intramuscular] has an effect size that is actually a little larger than the effect that we would expect with haloperidol or lorazepam intramuscularly based on indirect comparisons. I gave that presentation, and I've been giving that presentation for quite some time, and it hasn't gotten as much traction as I thought it would have. So perhaps another way of addressing this is maybe something entirely different that doesn't involve an intramuscular injection.

So what if something that was given by mouth would work just as fast? There is some evidence available about sublingual asenapine as potentially being helpful in reducing agitation -- as tested in a clinical trial of about 100 people in Syracuse, New York, where people were randomized to receive either sublingual asenapine 10 mg or an equally bad-tasting sublingual as placebo. And what was measured was agitation through the Positive and Negative Syndrome Scale [PANSS] Excited Component.

It turns out with all comers coming to the ED [emergency department] who had some degree of agitation and were willing to provide informed consent, they experienced a reduction in their agitation fairly quickly -- evident as early as 15 minutes after administration. So there is a potential for oral administration, albeit sublingually absorbed, to decrease agitation.

In the pipeline is dexmedetomidine film. Dexmedetomidine is an anesthetic agent that has been used for quite some time. And it was recently reformulated as a sublingual film that can be given in people with schizophrenia or bipolar disorder who are agitated. It's also being tested in people with Alzheimer's disease who are agitated. In the schizophrenia and bipolar agitation studies, reduction in agitation was notable and met the primary endpoint of a statistically significant and clinically relevant reduction of agitation at 2 hours after administration. The effects were quite striking and on par with what we would expect with something we would inject.

So in terms of managing agitation in schizophrenia and bipolar disorder, what we've had that's been available for quite some time leaves somewhat to be desired, in terms of haloperidol lorazepam. I didn't really describe why, but basically giving haloperidol means ultimately sometimes having to give an anti-cholinergic agent for an acute dystonic reaction. And in the end, are we really going to want to continue giving haloperidol as a foundational treatment?

What's new? Well what's new-ish or new-er, are the second generation short-acting or fast-acting intramuscular preparations. But they've sort of not been adopted as much as we had thought. And in the future, what's next? Maybe an oral administration of something different that would be more acceptable to people and help our lives in treating patients with agitation where it is so common in the EDs and inpatient units. We need to have something that works and is easily attainable and accessible. Dr. Meyer, in your capacity, and as a consultant to the state hospital system in California, what are your thoughts on this?

Meyer: I think we would like to get away from the need for intramuscular, if at all possible. People have shown the feasibility of using oral antipsychotics. There's a famous study by Glenn Currier 22 years ago, which showed that if you can get the person to ingest the antipsychotic, it's going to be effective. And I think having alternatives both in the delivery route and also the alternatives to D2 blockade are really important. And I think we're kind of excited about whether the dexmedetomidine is really going to work out, and in what types of patients. It seems well tolerated, doesn't seem to have the orthostasis risk that many were concerned about. So we'll keep our fingers crossed.

Kane: And if I could add, I think that having an alternative to the IM injection, I think it's very valuable for many patients. Because that is kind of a turn-off. And also when we approach them about a long-acting injectable medicine, they sometimes think about these acute experiences very negatively, and that leaves a kind of bad taste.

Comment