Sublingual Dexmedetomidine for the Treatment of Acute Agitation in Adults With Schizophrenia or Schizoaffective Disorder: A Randomized Placebo-Controlled Trial

Objective: Determine if sublingual dexmedetomidine, a selective alpha(2) adrenergic receptor agonist, reduces symptoms of acute agitation associated with schizophrenia or schizoaffective disorder. Methods: This phase 3, randomized, double-blind, placebo-controlled study was conducted in adults diagnosed with schizophrenia or schizoaffective disorder per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. The study was conducted at 15 US sites between January 23, 2020, and May 8, 2020. Participants were randomized to sublingual dexmedetomidine 180 mu g, 120 mu g, or matching placebo. The primary efficacy endpoint was mean change from baseline in the Positive and Negative Syndrome Scale-Excited Component (PEC) total score at 2 hours postdose. Results: Altogether, 380 participants (mean age 45.6 years, 63.4% identifying as male, 77.9% identifying as Black or African American) were randomized; 380 (100%) self-administered study medication, and 372 (97.9%) completed the study. The mean PEC total score at baseline (17.6) indicated mild to moderate agitation. At 2 hours postdose, the least squares mean changes (SE) from baseline were -10.3 (0.4) for sublingual dexmedetomidine 180 mu g, -8.5 (0.4) for 120 mu g, and -4.8 (0.4) for placebo. Least squares mean differences (97.5% confidence intervals) in the sublingual dexmedetomidine groups were -5.5 (-6.7 to -4.3) for 180 mu g and -3.7 (-4.9 to -2.5) for 120 mu g (both P <.001 vs placebo). The most commonly encountered adverse events with dexmedetomidine (incidence >= 5% and >= 2x rate observed with placebo) were somnolence, dry mouth, and hypotension for the 120 mu g dose, and somnolence, dizziness, orthostatic hypotension, and oral hypoesthesia for the 180 mu g dose. Conclusions: Treatment with sublingual dexmedetomidine 180 mu g or 120 mu g was more efficacious than placebo in reducing acute agitation associated with schizophrenia as measured by PEC scores at 2 hours postdose.