A Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose, Multicenter Study of Pregabalin in Patients With Generalized Anxiety Disorder

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.

Use of pregabalin for therapy of patients with generalised anxiety disorder - pilot investigation: Review of case studies

“…Kliničke studije ukazuju da je efikasan i u uklanjanju kognitivnih i somatskih simptoma anksiznosti, a da mu je efikasnost uporediva sa efikasnošću benzodiazepina i antidepresiva [8,9,10,11,12]. Dobre osobine su mu to što ima blage sporedne efekte koje pacijenti lako podnose i to što može uspešno i sigurno da se kombinuje sa drugim lekovima koji se koriste kod pacijenata sa generalizovanim anksioznim poremećajem [13].…”

“…Naime, u većini navedenih studija došlo je do komparabilnog umanjenja skora na primenjenim instrumentima za procenu kliničkog stanja pacijenata [11,12,16]. Međutim, problem ovakvog tumačenja rezultata je u tome što, do sada nije bilo publikovanih studija koje su ispitivale efikasnost pregabalina a da je u metodologiji procene stanja kod pacijenata prikazanoh u našem uzorku korišćen GAD-7 upitnik.…”

A Meta-Analysis of the Efficacy of Pregabalin in the Treatment of Generalized Anxiety Disorder

“…10 The half-life of pregabalin from a single dose is between 4.6 and 6.8 hours. 18 A total of 7 published RCTs [19][20][21][22][23][24][25] have investigated the efficacy of pregabalin in the treatment of adult GAD. One of these RCTs specifically examined the efficacy of pregabalin in GAD in older adults.…”

“…This earlier effect size was based on a meta-analysis involving only the first 2 RCTs. 19,20 In Figure 1, none of the additional 5 RCTs published since have demonstrated effects as large as those from these first 2 studies. Larger samples used in these later studies have resulted in a substantially reduced estimate of the efficacy of pregabalin in GAD, suggesting that these earlier results may have led to an overestimate of the efficacy and effectiveness of the drug.…”

“…The results for the effect of pregabalin on HARS scores in GAD were based on only 2 RCTs, 19,20 with each of these running for only 4 weeks. A further weakness of this meta-analysis is that the authors presented only the effect sizes from the total score of the HARS, and did not examine the effect of pregabalin on psychic anxiety and somatic anxiety factors.…”