Abstract

To evaluate acute onset of anxiolytic activity using a dental anxiety model, 89 patients were randomised to double-blind single dose pregabalin 150 mg, alprazolam 0.5 mg or placebo 4 h before a scheduled dental procedure. A Dental Anxiety Total score >12 (moderate-to-severe) without meeting Diagnostic and Statistical Manual of Mental Disorders (Fourth edition) (DSM-IV) anxiety disorder criteria was required. Efficacy and safety, assessed 2, 2.5, 3, 3.5 and 4 h postdose, included 100 mm Visual Analogue Scale for Anxiety (VAS-Anxiety; primary outcome), 100 mm VAS-Sedation and Time-to-Onset of Action Scale (TOAS), a patient-rated anti-anxiety drug-benefit scale (no [0] to full benefit [10]). Mixed model analysis found significantly greater VAS-A improvement slopes for pregabalin (t = -2.47; P = 0.014) and alprazolam (t = -2.39; P = 0.018). There was a significant improvement versus placebo in the TOAS from 2 h through endpoint in alprazolam patients and from 3 h onward in pregabalin patients. Pregabalin produced significantly greater increases in VAS-Sedation versus placebo from 2.5 h through 4 h (2 h onward for alprazolam). Notably, there was a higher correlation between TOAS and VAS-Sedation (r = +0.58) than VAS-Anxiety (r = -0.50) on Spearman's analysis. The majority of Adverse Effects (AEs) were mild, and the most frequent for pregabalin, alprazolam, and placebo, respectively, were fatigue (N = 7, 7, 3), dizziness (N = 6, 3, 3), attention disturbance (N = 3, 1, 0), somnolence (N = 3, 0, 0), feeling abnormal (N = 0, 2, 0) and balance disorder (N = 0, 2, 0). These results suggest that onset of clinically meaningful anxiolytic effect after single-dose pregabalin occurs within the first 3-4 h. Additional research is needed to determine whether anxiolytic effect occurs in generalized anxiety disorder populations by day 1 or within 3-4 h post-first dose.