Early onset anxiolytic efficacy after a single dose of pregabalin: double-blind, placebo- and active-comparator controlled evaluation using a dental anxiety model

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.

Effects of ascorbic acid on anxiety state and affect in a non-clinical sample

“…Interestingly, pregabalin present a rapid anxiolytic effect (Nutt et al 2009), similar to the effect presented in this work. While pregabalin can decrease the release of glutamate (Martinotti et al 2013), ascorbic acid can impair the glutamate binding to the NMDA receptor (Majewska et al 1990).…”

Evaluation of Pregabalin as an Adjuvant to Patient-controlled Epidural Analgesia during Late Termination of Pregnancy

“…These results raise the question of whether pregabalin might have an anxiolytic effect within the first hours after a single-dose administration by contrast with the efficacy demonstrated during long-term treatment of generalized anxiety disorder. 4,5 Nutt et al 25 have found that a preoperative dose of pregabalin 150 mg provided a clinically meaningful anxiolytic effect within 4 h of intake, although the speed of response was not as rapid as it was after administration of alprazolam, an active placebo. The difference among the aforementioned studies relies on the fact that Nutt et al 25 have evaluated patients' anxiety for several hours after pregabalin intake, whereas in the negative studies, 15,24 the authors have assessed anxiety state only at 1 h after pregabalin administration.…”

Anxiety disorders

“…9 Relative to SSRIs or SNRIs, pregabalin may have an early onset of effect: a study in healthy volunteers found anxiolytic effects within 3e4 h following a single dose. 10 It is generally well tolerated with few drug interactions and a low rate of discontinuation symptoms, and can prevent relapse over 24 weeks. 11 Sleep disturbance is common in GAD, and pregabalin reduces sleep disturbance, both directly, and indirectly via the reduction of anxiety.…”