New Treatment for Acute Agitation

The FDA has approved dexmedetomidine sublingual film for the treatment of agitation associated with schizophrenia or Bipolar I/II disorder in adults.  

When agitation and aggression are severe, swift resolution of the situation is required.

Introduction:

Since the advent of chlorpromazine in the 1950’s pharmacological intervention has been a mainstay in these acute situations. In many cases the combination of haloperidol, lorazepam, and diphenhydramine, the so called B-52 are administered intramuscularly when quick resolution of agitation is required for the safety of the person and staff. 

But what happens when these methods fail to provide adequate relief and person remains agitated?

There are few options available outside of the dopamine blocking medications and benzodiazepines. 

I’ve been in situations as an early career psychiatrist where I’ve had to treat severe agitation that is unresponsive to the traditional methods of treating agitation. 

After multiple medications failed to adequately treat the agitation, I called the medical floor to transfer the person for a Dexmedetomidine (precedex) drip. This is a medication I’ve seen work well in the ICU setting with agitated delirium. 

But drips are complicated to use and require careful monitoring on the medical floor. I was thinking it would be great if there was an option that did not require IV placement or transfer to the medical floor. 

Mechanism of Action:

Recent studies have looked at sublingual Dexmedetomidine as a potential new treatment for agitation. 

Dexmedetomidine is an alpha-2 noradrenergic agonist approved by the FDA for IV sedation and analgesia and limitted to 24 hours. It induces sleep by activating alpha-2 presynaptic receptors reducing norepinephrine release. Both sedation and awakening are rapid, and the medication is safe but does require monitoring of blood pressure and heart rate. 

Phase 3 Clinical Trial Results:

A phase 3 clinical trial of 120 micrograms and 180 micrograms of sublingual dexmedetomidine was compared to placebo in patients with bipolar disorder. They used the excited portion (PEC) of the PANSS to measure efficacy and found a response beginning at 20 minutes and continuing to 120 minutes at both doses. 90% of participants in the 180 microgram and 76% in the 120 microgram groups achieved a response. No significant adverse events occurred in the treatment groups.  

Hsiao JK. Sublingual Dexmedetomidine as a Potential New Treatment for Agitation. JAMA. 2022;327(8):723–725. doi:10.1001/jama.2021.21313