Agitation Associated with Schizophrenia or Bipolar Disorder: Sublingual Dexmedetomidine Film Efficacy by Baseline Agitation Level

This work was sponsored by BioXcel Therapeutics If behavioral de-escalation of agitation associated with schizophrenia or bipolar disorder is unsuccessful, ideal pharmacologic treatment reduces agitation without excess sedation. Sublingual dexmedetomidine (DSF) is a mucoadhesive, orally absorbed film, approved to treat agitation in adults with schizophrenia or bipolar disorder I or II. This post hoc analysis of data from 2 randomized, double-blind trials evaluates efficacy of DSF by baseline agitation severity. 758 adults with agitation associated with schizophrenia or bipolar disorder who scored ≥14 on the Positive and Negative Symptom Scale-Excited Component (PEC) and ≥4 on ≥1 PEC item self-administered 180mcg, 120mcg or placebo. Primary outcome was 2-hour PEC change; secondary was time of separation from placebo. For this post hoc analysis, efficacy data were stratified into mild/moderate baseline agitation (CGI-S 3-4) and marked/severe baseline agitation (CGI-S 5-6). Significant improvement in agitation began as early as 20 minutes at 180mcg and 30 minutes at 120mcg. Baseline patient CGI-S ratings were mild/11%, moderate/68%, marked/20%, and severe/1%. Post hoc analysis showed statistically significant reduction in agitation with DSF in both baseline agitation groups. There were no severe or serious treatment-related adverse events and the most common AEs were somnolence/21.5%, dry mouth/5.9%, hypotension/5.3%, dizziness/4.9%, orthostatic hypotension/4.0%, and oral hypoesthesia/3.8%. No patient was unarousable. Dexmedetomidine sublingual film reduced agitation symptoms as early as 20 minutes at 180mcg group and 30 minutes at 120mcg, regardless of baseline agitation severity. The most common AEs were somnolence, dry mouth, hypotension, dizziness, orthostatic hypotension, oral hypoesthesia. Most somnolence was mild; all patients were awake or arousable.