P0081 - Rapid onset anxiolytic efficacy after a single dose of Pregabalin: Dou-ble-blind, placebo-controlled evaluation using a dental anxiety model

Abstract

Background and Aims:

To assess the speed of onset of anxiolytic efficacy of a single-dose of pregabalin (PGB) in a dental-anxiety model.

Methods:

Adult outpatients in this double-blind, parallel-group study received a single-dose PGB 150mg (n=27), alprazolam 0.5mg (n=31; ALP), or placebo (n=31; PBO) 4 hours before a dental procedure. Inclusion criteria included Dental Anxiety Total score ≥12 (moderate-to-severe) without presence of DSM-IV anxiety disorder. Efficacy and safety assessments (at 2, 2.5, 3, 3.5, and 4 hours post-dose) included: 100-mm Visual Analogue Scale for Anxiety (VAS-A; primary outcome); 100-mm VAS-Sedation (VAS-S); and Time-to-Onset of Action Scale (TOAS), which rates anti-anxiety drug benefit (0-10, no–full benefit).

Results:

VAS-A scores at baseline were higher on PGB (70.2) compared to ALP (57.4) or PBO (64.1). On a mixed-model analysis, VAS-A improvement slopes were greater for PGB (t= -2.47; P=0.014) and ALP (t= -2.39; P=0.018) vs PBO. Significant improvement on TOAS was seen at hour 2 and hour 3 through endpoint for ALP and PGB subjects, respectively (P≤0.05 vs PBO, both groups). VAS-S scores were significantly higher vs PBO for PGB at hours 2.5-4.0, and at hours 2 until endpoint for ALP (P≤0.05 both groups). Spearman analysis showed similar levels of correlation between the TOAS and VAS-S (r= +0.58) and VAS-A (r= -0.50), suggesting that the VAS-S may be measuring an efficacy outcome in this model. Both PGB and ALP were well-tolerated.

Conclusion:

Clinically meaningful anxiolytic effect occurred within 3-4 hours after single-dose PGB in this dental-anxiety model.