Dexmedetomidine nasal spray for acute agitation in adults with bipolar disorder: a single-arm open-label trial

Sublingual dexmedetomidine, a selective α2 adrenergic receptor agonist, has been shown in phase 3, randomized, double-blind, placebo-controlled trial to reduce symptoms of acute agitation associated with schizophrenia and bipolar disorder. However, administration via the sublingual route may be challenging in some acutely agitated patients due to cooperation or swallowing difficulties. Intranasal delivery offers potential operational advantages in such setting and may allow more rapid systemic absorption. This early-phase, single-arm study aimed to explore the feasibility, preliminary tolerability, and within-subject changes in agitation severity with dexmedetomidine nasal spray in bipolar disorder.

In this single-center single-arm, open-label study, 23 patients with bipolar disorder (DSM-5 criteria) and acute agitation were enrolled, and 20 received a single dose of dexmedetomidine nasal spray (100 μg) in a hospital setting. The primary efficacy endpoint was the mean change from baseline in the Positive and Negative Syndrome Scale-Excited Component (PEC) total score at 2 h post-treatment.

The mean baseline PEC total score (16.6) indicated mild to moderate agitation. At 2 h post-dose, the least squares mean changes (SE) from baseline were -7.3 (4.5). The response rate (≥40 % PEC reduction) was 75 %. Observed symptom relief began as early as 10 min after medication. The most common adverse events included hypotension (15 %), hypertension (5 %), decreased heart rate (10 %), and increased heart rate (5 %).

In this small, uncontrolled feasibility study, dexmedetomidine nasal spray was well tolerated and associated with within-subject reduction in agitation severity at 2 h. These finding should be interpreted as hypothesis-generating, and larger randomized controlled trials are needed to establish safety, efficacy, and generalizability.