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Sublingual dexmedetomidine can curb agitation in bipolar disorder

Reuters Health - 28/02/2022 - In patients with bipolar disorder, self-administered sublingual dexmedetomidine reduced mild-to-moderate agitation for up to two hours in a phase 3, placebo-controlled trial. 

Dexmedetomidine is an alpha2-adrenergic receptor agonist approved in intravenous form for procedural sedation and anesthesia. 

When treating agitation, "the goal is to prevent escalation first by various behavioral de-escalation techniques," Dr. Sheldon Preskorn of Kansas University School of Medicine-Wichita told Reuters Health by email. "When that is not effective, medications can be given." 

"At a mild-to-moderate level of agitation, patients can recognize their agitation, be distressed by it and want relief. That was the case for the participants in our study," he said. "They were able to reliably apply the sublingual film, which adheres to the oral mucosa until it dissolves." 

As reported in JAMA, Dr. Preskorn and colleagues randomly assigned 362 adults with bipolar I or II disorder (mean age, about 46; 55% women; 56% Blacks) to sublingual dexmedetomidine 180 mcg or 120 mcg or placebo. 

The primary efficacy end point was the mean change from baseline at 2 hours in the Positive and Negative Syndrome Scale-Excited Component (PEC) total score. The range of possible total scores is 5 (absence of agitation) to 35 (extremely severe). 

Participants' baseline agitation was mild-to-moderate, with an overall mean PEC total score of 18. 

Two hours after taking the medication, the mean changes from baseline in PEC total score were −10.4 for the 180 mcg dose; −9.0 for 120 mcg; and −4.9 for placebo. 

The percentage of participants with a PEC response at 2 hours, defined as a reduction of at least 40%, was 90.5% with 180 mcg; 77% with 120 mcg, and 46% with placebo. 

For those receiving either dose of sublingual dexmedetomidine, treatment effects began 20 minutes after taking the medication. 

Adverse events occurred in 35.7% of patients taking 180 mcg; 34.9% taking 120 mcg, and 17.5% taking placebo. The most common adverse events in the 180 mcg, 120 mcg, and placebo groups, respectively, were somnolence (21.4% vs. 20.6% vs. 4.8%); dry mouth (4.8% vs. 7.1% vs. 0.8%); hypotension (6.3% vs. 4.8% vs. 0%); and dizziness (5.6% vs. 5.6% vs. 0.8%). 

The authors conclude, "Further research is needed to understand the spectrum of patients for whom this treatment would be effective and feasible and to better understand the clinical importance of the observed effect size." 

Dr. Preskorn added, "The next step for this investigational product is for the FDA to determine whether it is approvable." A response to the new drug application is expected by April 5, 2022, he said. 

Dr. John Hsiao of the National Institutes of Health in Bethesda, author of a related editorial, commented in an email to Reuters Health, "This is a new, potentially important addition to the psychotropic armamentarium for agitation. (It) works very well in ICUs for agitated delirium but hasn't been tried before for sedation in the psychiatric or emergency room setting. The sublingual formulation is useful but the idea of using (sublingual dexmedetomidine) to manage agitation is what's novel and important." 

With regard to self-administration, he noted, "It's hard to get informed consent in an agitated patient. However, (the drug) definitely reduced agitation in these bipolar patients, which suggests (it) should also help in someone less cooperative. However, some degree of cooperation is needed with a sublingual med." 

"We'll have to wait and see if, and how well (sublingual dexmedetomidine) works in real-world psychiatric and ER settings," he concluded. 

The study was funded by BioXcel Therapeutics Inc. Dr. Preskorn and many of the coauthors received funds from the company and one is an employee. 

SOURCE: https://bit.ly/35aGxsh and https://bit.ly/3K3O6zD  JAMA, online February 22, 2022.

By Marilynn Larkin  


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