Efficacy and Safety of Pregabalin in the Treatment of Generalized Anxiety Disorder: A 6-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Comparison of Pregabalin and Venlafaxine

Stuart A. Montgomery, M.D., Ph.D.; Kathy Tobias, M.D.; Gwen L. Zornberg, M.D., Sc.D.; Siegfried Kasper, M.D., Ph.D.; and Atul C. Pande, M.D.

Objective: Pregabalin has demonstrated robust, rapid efficacy in reducing symptoms of generalized anxiety disorder (GAD) in 4 placebo-controlled clinical trials. The current study compared the efficacy and safety of pregabalin and venlafaxine in patients diagnosed with moderate to severe GAD.

Method: The study was conducted from December 21, 1999, to July 31, 2001. Outpatients (N = 421) in primary care or psychiatry settings meeting DSM-IV criteria for GAD were randomly assigned to 6 weeks of double-blind treatment with pregabalin 400 or 600 mg/day, venlafaxine 75 mg/day, or placebo. The primary analysis was change in Hamilton Rating Scale for Anxiety (HAM-A) total score from baseline to last-observation-carried-forward (LOCF) endpoint. Secondary analyses included the change in HAM-A psychic (emotional) and somatic (physical) factor scores, significant improvement at week 1, and week 1 improvement sustained at every visit through endpoint.

Results: Pregabalin at both dosages (400 mg/day, p = .008; 600 mg/day, p = .03) and venlafaxine (p = .03) produced significantly greater improvement in HAM-A total score at LOCF endpoint than did placebo. Only the pregabalin 400-mg/day treatment group experienced significant improvement in all a priori primary and secondary efficacy measures. Pregabalin in both dosage treatment groups (400 mg/day, p < .01; 600 mg/day, p < .001) significantly improved HAM-A total score at week 1, with significant improvement through LOCF endpoint. Statistically significant improvement began at week 2 for venlafaxine. Discontinuation rates due to associated adverse events were greatest in the venlafaxine treatment group: venlafaxine, 20.4%; pregabalin 400 mg/day, 6.2%; pregabalin 600 mg/day, 13.6%; placebo, 9.9%.

Conclusion: Pregabalin was safe, well tolerated, and rapidly efficacious across the physical-somatic as well as the emotional symptoms of GAD in the majority of patients studied in primary care and psychiatric settings.

(J Clin Psychiatry 2006;67:771-782)

Received Sept. 28, 2005; accepted Feb. 6, 2006. From Imperial College School of Medicine, London, U.K. (Dr. Montgomery); Pfizer Global Research and Development, Ann Arbor, Mich. (Drs. Tobias and Pande); Pfizer Global Pharmaceuticals, Pfizer Inc, New York, N.Y. (Dr. Zornberg); and the Department of General Psychiatry, Medical University, Vienna, Austria (Dr. Kasper). Dr. Zornberg is now with the Health Committee of the New York City Board of Corrections, New York, N.Y.

This study was funded by Pfizer Inc, New York, N.Y.

Data from this study were presented at the 155th annual meeting of the American Psychiatric Association, May 18-23, 2002, Philadelphia, Pa.; the 42nd annual New Clinical Drug Evaluation Unit meeting, June 10-13, 2002, Boca Raton, Fla.; the 15th European Congress on Neuropsychopharmacology, October 5-9, 2002, Barcelona, Spain; and the 16th U.S. Psychiatric and Mental Health Congress, November 6-9, 2003, Orlando, Fla.

Dr. Montgomery has been a consultant for, received honoraria from, and served on the speakers or advisory boards for Wyeth, Lundbeck, and GlaxoSmithKline. Dr. Tobias is an employee of Pfizer. Dr. Zornberg has been an employee of Pfizer. Dr. Kasper has received grant/research support from Eli Lilly, Lundbeck, Bristol-Myers Squibb, GlaxoSmithKline, Organon, and Servier; has been a consultant or served on the advisory boards for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, Lundbeck, Pfizer, Organon, Janssen, and Novartis; and has served on the speakers bureau for AstraZeneca, Eli Lilly, Lundbeck, and Janssen. Dr. Pande is an employee of and a major stock shareholder in Pfizer.

The authors wish to thank Agnes Marchand, M.Sc., Ed Whalen, Ph.D., Kem Phillips, Ph.D., Jerri Brock, M.S., and the members of the CI-1008-087 Study Group (a full list of investigators appears at the end of this manuscript).

Corresponding author and reprints: Stuart A. Montgomery, M.D., Ph.D., P.O. Box 8751, London W13 8WH, UK (e-mail: Stuart@samontgomery.co.uk).