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Abstract

Pregabalin is a novel compound under development for the treatment of several types of anxiety disorders. To obtain an initial evaluation of the efficacy and safety of pregabalin in the treatment of generalized anxiety disorder (GAD), we conducted a double-blind, fixed-dose, parallel-group, placebo and active-controlled multicenter 4-week study that compared 271 patients randomized to receive pregabalin 50 mg tid (N = 70), pregabalin 200 mg tid (N = 66), placebo (N = 67), or lorazepam 2 mg tid (N = 68), followed by a 1-week double-blind taper. The primary efficacy parameter was change from baseline to endpoint (last observation carried forward) in the Hamilton Anxiety Scale (HAM-A) total score; adjusted mean change scores on the HAM-A were significantly improved for pregabalin 200 mg tid (difference of 3.90 between drug and placebo; p = 0.0013 [ANCOVA], df = 252) and for lorazepam (difference of 2.35; p = 0.0483 [ANCOVA], df = 252), with the significant difference between the pregabalin 200 mg tid and placebo groups seen at week 1 of treatment (p = 0.0001 [ANCOVA], df = 238). Safety analysis, which included assessment of spontaneously reported adverse events, laboratory monitoring, and withdrawal symptoms, showed pregabalin to be generally well-tolerated. The most common adverse events seen with pregabalin 200 mg tid were somnolence and dizziness. They were usually mild or moderate in intensity and were often transient. Pregabalin-treated patients had a higher completion rate than lorazepam-treated patients. This study supports the hypothesis that pregabalin is effective and safe in short-term therapy for GAD. More studies are needed to determine the best dosing regimen to optimize efficacy and tolerability.

A cost-utility analysis of pregabalin versus venlafaxine XR in the treatment of generalized anxiety disorder in Portugal

“…Furthermore, the trial considered is the only one comparing flexible doses of pregabalin and venlafaxine XR, which is a more appropriate approach than assuming fixed doses. The placebo-adjusted effect size of pregabalin in this trial is similar to the effect estimated in other trials [28-32]. …”

GABAergic Contributions to the Pathophysiology of Depression and the Mechanism of Antidepressant Action

“…However, the pregabalin's effect on TMS measures of SICI and LICI or CSP suggests GABAB activation, and the drug generates an excitability pattern similar to that seen for tiagabine [237]. Early preliminary data suggests pregabalin, an analogue of gabapentin, is effective and safe in the short-term as therapy for generalized anxiety disorder [238,239]. In multi-center, placebo-controlled comparator trials, pregabalin appears to have comparable efficacy to benzodiazepines in generalized anxiety disorder [240].…”

Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders

“…Pregabalin: The anticonvulsant pregabalin was more effective than placebo in RCTs [576,577,592,593,597,613] and as effective as benzodiazepines [592,593,597] in patients with GAD (Level 1). Pregabalin was more effective than venlafaxine XR in one RCT [577], but equivalent in another [576].…”

“…Benzodiazepines: Alprazolam [589-593], bromazepam [589,594], diazepam [583,589,595,596], and lorazepam [589,593,597-601] all have demonstrated efficacy for the treatment of GAD (all Level 1). While these agents have level 1 evidence for efficacy, they are recommended as second-line therapy, and usually only for short-term use, because of side effects, dependence, and withdrawal issues.…”