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A method for controlling for a high placebo response rate in a comparison of venlafaxine XR and diazepam in the short-term treatment of patients with generalised anxiety disorder

Published online by Cambridge University Press:  16 April 2020

David Hackett ,
Vincent Haudiquet  and
Eliseo Salinas
David Hackett*
Affiliation:
Wyeth Research, 80, avenue du Général-de-Gaulle, Paris La Défense, France
Vincent Haudiquet
Affiliation:
Wyeth Research, 80, avenue du Général-de-Gaulle, Paris La Défense, France
Eliseo Salinas
Affiliation:
Wyeth Research, 80, avenue du Général-de-Gaulle, Paris La Défense, France
*
*E-mail address: [email protected]
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Abstract

This randomised, double-blind, placebo-controlled study compared the efficacy of venlafaxine XR (75 or 150 mg/d) with diazepam (15 mg/d) over an 8-week treatment period in 540 non-depressed outpatients with generalised anxiety disorder (GAD). At week 8, significant improvements from baseline were observed in the venlafaxine XR, diazepam and placebo groups. Although these improvements were higher in the first two groups than in the placebo group for each of the primary efficacy variables (Hamilton Rating Scale for Anxiety (HAM-A) total, HAM-A psychic anxiety factor, Hospital Anxiety and Depression Scale (HAD) anxiety sub-scale and Clinical Global Impression (CGI) improvement), there were no statistically significant differences between groups. These non-positive results were thought to be due to the very high placebo response observed in some centres. To understand the variability of the study, a secondary preplanned analysis was performed. This involved sub-dividing the study centres according to their ability to detect a two-point mean difference between diazepam and placebo at week 8 on the HAM-A total score. Centres able to show such a difference were termed verum-sensitive. Improvements from baseline to week 8 in venlafaxine XR-treated patients from verum-sensitive centres were significantly greater than in placebo on each of the primary efficacy measures (P ≤ 0.05). This suggests that those centres able to detect an anxiolytic effect of diazepam were also able to detect an anxiolytic effect of venlafaxine XR. Significant differences in baseline demographics, rates of adverse event reporting and rates of patient discontinuations were noted between patients enrolled at verum-sensitive and verum-insensitive sites. These results reflect the importance of study centre selection in accurately determining efficacy in placebo-controlled trials.

Keywords

DiazepamGeneralised anxiety disorderPlacebo responseVenlafaxine XRVerum-sensitive
Type
Original article
Information
European Psychiatry , Volume 18 , Issue 4 , June 2003 , pp. 182 - 187
Copyright
Copyright © Éditions scientifiques et médicales Elsevier SAS 2003

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References

Allgulander, C, Hackett, D, Salinas, E. Venlafaxine extended release (ER) in the treatment of generalised anxiety disorder. Br J Psychiatry 2001;179:17–24.10.1192/bjp.179.1.15CrossRefGoogle ScholarPubMed
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th. Washington (DC): APA; 1994.Google Scholar
Davidson, JR, DuPont, RL, Hedges, D, Haskins, JT. Efficacy, safety, and tolerability of venlafaxine extended-release and buspirone in outpatients with generalized anxiety disorder. J Clin Psychiatry 1999;60:528–35.10.4088/JCP.v60n0805CrossRefGoogle ScholarPubMed
Gelenberg, AJ, Lydiard, RB, Rudolph, RL, Aguiar, L, Haskins, JT, Salinas, E. Efficacy of venlafaxine extended-release capsules in non-depressed outpatients with generalized anxiety disorder. A 6-month randomized controlled trial. JAMA 2000;283:3082–8.Google Scholar
Lader, M. Anxiolytic drugs: dependence, addiction and abuse. Eur Neuropsychopharmacol 1994;4:85–91.10.1016/0924-977X(94)90001-9CrossRefGoogle Scholar
Niklson, IA, Reimitz, P- E, Sennef, C. Factors that influence the outcome of placebo-controlled antidepressant trials. Psychopharmacol Bull 1997;33:41–51.Google Scholar
Piercy, MA, Sramek, JJ, Kurtz, NM, Cutler, NR. Placebo response in anxiety disorders. Ann Pharmacother 1996;30:1013–9.Google ScholarPubMed
Rickels, K, Case, GW, Winokur, A, Swenson, C. Long-term benzodiazepine therapy: benefits and risks. Psychopharmacol Bull 1984;20:608–15.Google ScholarPubMed
Rickels, K, Pollack, MH, Sheehan, DV, Haskins, JT. Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder. Am J Psychiatry 2000;157:968–74.10.1176/appi.ajp.157.6.968CrossRefGoogle ScholarPubMed
Robinson, DS, Rickels, K. Concerns about clinical drug trials. J Clin Psychopharmacol 2000;20:593–6.10.1097/00004714-200012000-00001CrossRefGoogle ScholarPubMed
Shader, RI, Greenblatt, DJ. Use of benzodiazepines in anxiety disorders. New Engl J Med 1993;328:1398–405.Google ScholarPubMed
Storosum, JG, Elferink, AJA, Van Zwieten, BJ, van dem Brink, W, Gersons, BPR, van Strik, R, et al. Short-term efficacy of tricyclic antidepressants revisited. A meta-analytic study. Eur Neuropsy-chopharamacol 2001;11:173–80.CrossRefGoogle ScholarPubMed
Wilcox, CS, Cohn, JB, Linden, RD, Heiser, JF, Lucas, PB, Morgan, DL, et al. Predictors of placebo response: a retrospective analysis. Psychopharmacol Bull 1996;28:157–62.Google Scholar
Wittchen, H- U, Hoyer, J. Generalized anxiety disorder: nature and course. J Clin Psychiatry 2001;62 (Suppl 11):15–9.Google ScholarPubMed
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