This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Hidalgo, R. B. Articles by Davidson, J. R. T. Search for Related Content PubMed PubMed Citation Articles by Hidalgo, R. B. Articles by Davidson, J. R. T. Pubmed/NCBI databases Medline Plus Health Information Anxiety Social Bookmarking                         What's this?

An effect-size analysis of pharmacologic treatments for generalized anxiety disorder

Anxiety and Traumatic Stress Program, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA

Larry A. Tupler

Anxiety and Traumatic Stress Program, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA

Jonathan R. T. Davidson

Anxiety and Traumatic Stress Program, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA, david011{at}mc.duke.edu

Generalized anxiety disorder (GAD) is a prevalent and impairing disorder, associated with extensive psychiatric and medical comorbidity and usually characterized by a chronic course. Different drugs have been investigated in GAD; among them are the following: 1) SSRIS: paroxetine, sertraline, fluvoxamine and escitalopram; 2) SNRI1S: venlafaxine; 3) benzodiazepines (BZS): alprazolam, diazepam and lorazepam; 4) azapirones (AZAS): buspirone; 5) antihistamines (AHS): hydroxyzine; 6) pregabalin (PGB); and 7) complementary/alternative medicine (CAM): kava-kava and homeopathic preparation. We conducted an effect size (ES) analysis of 21 double-blind placebo-controlled trials of medications treating DSM-III-R, DSM-IV or ICD-10 GAD using HAM-A change in score from baseline or endpoint score as the main efficacy measure. Literature search was performed using MEDLINE and PsycINFO databases including articles published between 1987 and 2003 and personal communications with investigators and sponsors. comparing all drugs versus placebo, the Es was 0.39. Mean Ess, excluding children, were PGB: 0.50, AH: 0.45, SNRI: 0.42, BZ: 0.38, SSRI: 0.36, AZA: 0.17 and CAM: -0.31. comparing ES for adults versus children/adolescents (excluding CAM) and conventional drugs versus CAM (excluding children/adolescents) we found significantly higher ES for children/adolescents and for conventional drugs (p < 0.001 and p < 0.01, respectively). No significant differences were found when comparing date of publication, location of site (i.e. US versus other), fixed versus flexible dosing, number of study arms, or number of outcome measures used. Medications varied in the magnitude of their Es, ranging from moderate to poor. AdolesCents and Children showed a muCh greater ES Compared with adultS. SubjeCts taking CAM had worse outComes than plaCebo.

Key Words: GAD • pharmaCologiC treatment • effeCt size • meta-analysis

References

• Allgulander C., Hackett D., Salinas E. (2001) Venlafaxine extended release (ER) in the treatment of generalised anxiety disorder: twenty-four-week placebo-controlled dose-ranging study. Br J Psychiatry 179: 15—22[Abstract/Free Full Text]
• Allgulander C., Dahl A.A., Austin C., Morris P L P, Sogaard J.A., Fayyad R., Kutcher S.P., Clary C.M. (2004) Efficacy of sertraline in a 12-week trial for generalized anxiety disorder Am J Psychiatry 161: 1642—1649[Abstract/Free Full Text]
• Bonne O., Shemer Y., Gorali Y., Katz M., Shalev A.Y. (2003) A randomized, double-blind, placebo-controlled study of classical homeopathy in generalized anxiety disorder. J Clin Psychiatry 64: 282—287[Web of Science][Medline] [Order article via Infotrieve]
• Cohen J. (1988) Statistical Power Analysis for the Behavioral Sciences (2nd edition). Lawrence Earlbaum Associates, Hillsdale, NJ, USA
• Connor K.M. and Davidson J R T (2002) A placebo-controlled study of kava kava in generalized anxiety disorder. Int Clin Psychopharmacology 17: 186—188
• Cooper H.M., Rosenthal R. (1990) Statistical versus traditional procedures for summarizing research findings. Psychol Bull 87: 442—449
• Davidson J R T, DuPont R.L., Hedges D., Haskins J.T. (1999) Efficacy, safety and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder. J Clin Psychiatry 60: 528—535[Web of Science][Medline] [Order article via Infotrieve]
• Davidson J R T, Bose A., Korotzer A., Zheng H. (2004) Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo controlled, flexible-dose study. Depression and Anxiety 19: 234—240[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Eisen J.L. (1998) Course and psychosocial impairment in GAD. Presented at 151st Annual Meeting of the American Psychiatric Association
• Feltner D.E., Crockatt J.G., Dubovsky S.J. (2003) A randomized, double-blind, placebo-controlled, fixed dose, multicenter study of pregabalin in patients with generalized anxiety disorder. J Clin Psychopharmacol 23: 240—249[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Ferreri M., Darcis T., Burtin B., and the French Study Group for Hydroxyzine (1995) A multicentre double-blind placebo-controlled study investigating the anxiolytic efficacy of hydroxyzine in patients with generalized anxiety. Human Psychopharmacology 10: 181—187[CrossRef][Web of Science]
• Gelenberg A., Lydiard B.R., Rudolph R., Aguiar L., Haskins J.T., Salinas E. (2000) Efficacy of venlafaxine extended release capsules in nondepressed outpatients with generalized anxiety disorder: a 6-month randomized controlled trial. JAMA 283: 3082—3088[Abstract/Free Full Text]
• Goodman W.K., Bose A., Wang Q. ( 2005) Treatment of generalized anxiety disorder with escitalopram: pooled results from double-blind, placebo-controlled trials. J Affect Disord 87: 161—167[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Greist J.H., Jefferson J.W., Kobak K.A., Katzelnick D.J., Serlin R.C. (1995) Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder: a meta-analysis. Arch Gen Psychiatry 52: 53—60[Abstract/Free Full Text]
• Hackett D., Haudiquet V., Salinas E. (2003) 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. Eur Psychiatry 18: 182—187[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Hamilton M. (1959) The assessment of anxiety states by rating. Br J Med Psychology 32: 50—55[Web of Science][Medline] [Order article via Infotrieve]
• Hidalgo R.B., Barnett S.D., Davidson J R T (2001) Social anxiety disorder in review: two decades of progress. International J of Neuropsychopharmacol 4: 279—298[CrossRef]
• Hidalgo R.B., Davidson J R T (2001) Generalized anxiety disorder: an important clinical concern. Med Clin of North Am 85: 691—710[CrossRef]
• Khan A., Warner H., Brown W.A. (2000) Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials: an analysis of the Food and Drug Administration database. Arch Gen Psychiatry 57: 311—317[Abstract/Free Full Text]
• Khan A., Khan S.R., Walens G., Kolts R., Giller E. (2003) Frequency of positive studies among fixed and flexible dose antidepressant clinical trials: an analysis of the Food and Drug Administration summary basis of approval protocols. Neuropsychopharmacology 28: 552—557[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Lader M., Scotto J.C. (1998) A multicentre double-blind comparison of hydroxyzine, buspirone and placebo in patients with generalized anxiety disorder. Psychopharmacology 139: 402—406[CrossRef][Medline] [Order article via Infotrieve]
• Llorca P.M., Spadone C., Sol O., Danniau A., Bougerol T., Corruble E., Faruch M., Macher J.P., Sermet E., Servant D. (2002) Efficacy and safety of hydroxyzine in the treatment of generalized anxiety disorder: a 3-month double-blind study. J Clin Psychiatry 63: 1020—1027[Web of Science][Medline] [Order article via Infotrieve]
• Mitte K., Noack P., Steil R., Hautzinger M. (2005) A meta-analytic review of the efficacy of drug treatment in generalized anxiety disorder. J Clin Psychopharmacology 25: 141—150[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Möller H-J., Volz H-P., Reimann I.W., Stoll K-D. (2001) Opipramol for the treatment of generalized anxiety disorder: a placebo-controlled trial including an alprazolam-treated group. J Clin Psychopharmacol 21: 59—65[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• National Institute for Health and Clinical Excellence (NICE) (December 2004) Clinical guideline on depression. CG23 Depression: Appendix 20. Available online at: http://www.nice.org.uk/. Accessed 18 March 2006
• National Institute for Health and Clinical Excellence (NICE) (March 2005) Clinical guideline on PTSD. CG26 PTSD: Appendix 16b. Available online at: http://www.nice.org.uk/. Accessed 18 March 2006
• Otto M.W., Tuby K.S., Gould R.A., McLean R Y S, Pollack M.H. (2001) An effect-size analysis of the relative efficacy and tolerability of serotonin selective reuptake inhibitors for panic disorder. Am J Psychiatry 158: 1989—1992[Abstract/Free Full Text]
• Pande A.C., Crockatt J.G., Feltner D.E., Janney C.A., Smith W.T., Weisler R., Londborg P.D., Bielski R.J., Zimbroff D.L., Davidson J R T, Liu-Dumaw M. (2003) Pregabalin in generalized anxiety disorder: a placebo-controlled trial. Am J Psychiatry 160: 533—540[Abstract/Free Full Text]
• Pittler M.H., Ernst E. (2000) Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. J Clin Psychopharmacol 20: 84—89[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Pollack M.H., Zaninelli R., Goddard A., McCafferty J.P., Bellew K.M., Burnham D.B., Iyengar M.K. (2001) Paroxetine in the treatment of generalized anxiety disorder: results of a placebo-controlled, flexible-dosage trial. J Clin Psychiatry 62: 350—357[Web of Science][Medline] [Order article via Infotrieve]
• Rickels K., Pollack M.H., Sheehan D.V., Haskins J.T. (2000) Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder. Am J Psychiatry 157: 968—974[Abstract/Free Full Text]
• Rickels K., Rynn M.A. (2001) What is generalized anxiety disorder? J Clin Psychiatry 62: 4—12
• Rickels K., Zaninelli R., McCafferty J., Bellew K., Iyengar M., Sheehan D. (2003) Paroxetine treatment of generalized anxiety disorder: a double-blind, placebo controlled study. Am J Psychiatry 160: 749—756[Abstract/Free Full Text]
• Rynn M.A., Siqueland L., Rickels K. (2001) Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorder. Am J Psychiatry 158: 2008—2014[Abstract/Free Full Text]
• Stickel F., Baumuller H.M., Seitz K., Vasilakis D., Seitz G., Seitz H.K., Schuppan D. (2003) Hepatitis induced by Kava (Piper methysticum rhizona). J Hepatol 39: 62—66[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• The Research Units on Pediatric Psychopharmacology Anxiety Study Group (2002) The Pediatric Anxiety Rating Scale (PARS): development and psychometric properties. J of the Am Academy of Child & Adolescent Psychiatry 41: 1061—1069[CrossRef]
• Walkup J.T., Labellarte M.J., Riddle M.A., Pine D.S., Greenhill L., Klein R., Davies M., Sweeney M., Abikoff H., Hack S., Klee B., McCracken J., Bergman L., Piacentini J., March J., Compton S., Robinson J., O'Hara T., Baker S., Vitiello B., Ritz L.A., Roper M. (2001) Fluvoxamine for the treatment of anxiety disorders in children and adolescents. N Engl J Med 344: 1279—1285[Abstract/Free Full Text]
• Walsh B.T., Seidman S.N., Sysko R., Gould M. (2002) Placebo response in studies of major depression. JAMA 287: 1840—1847[Abstract/Free Full Text]
• Wittchen H-U., Zhao S., Kessler R.C., Eaton W.W. (1994) DSM-III-R generalized anxiety disorder in the National Comorbidity Survey. Arch of Gen Psychiatry 51: 355—364
• Yonkers K.A., Warshaw M.G., Massion A.O., Keller M.B. (1996) Phenomenology and course of generalised anxiety disorder. Br J Psychiatry 168: 308—313[Abstract/Free Full Text]
• Zimmerman M., Posternak M.A. (2003) Placebo response in antidepressant efficacy trials: relationship to number of active treatment groups, in 2003 Annual Meeting New Research Program and Abstracts. Arlington, VA, American Psychiatric Association, number 893

Journal of Psychopharmacology, Vol. 21, No. 8, 864-872 (2007)
DOI: 10.1177/0269881107076996


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				E. J. Lenze, B. L. Rollman, M. K. Shear, M. A. Dew, B. G. Pollock, C. Ciliberti, M. Costantino, S. Snyder, P. Shi, E. Spitznagel, et al. Escitalopram for Older Adults With Generalized Anxiety Disorder: A Randomized Controlled Trial JAMA, January 21, 2009; 301(3): 295 - 303. [Abstract] [Full Text] [PDF]

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Hidalgo, R. B. Articles by Davidson, J. R. T. Search for Related Content PubMed PubMed Citation Articles by Hidalgo, R. B. Articles by Davidson, J. R. T. Pubmed/NCBI databases Medline Plus Health Information Anxiety Social Bookmarking                         What's this?