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Efficacy of low and higher dose extended-release venlafaxine in generalized social anxiety disorder: a 6-month randomized controlled trial

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Abstract

Rationale

There is a need for new pharmacological treatments for generalized social anxiety disorder (GSAD), which is a common, often disabling condition.

Objective

To compare the efficacy and safety over 6 months duration of two dose ranges of venlafaxine extended-release (ER) with placebo in patients with GSAD.

Method

Twenty-eight-week, double-blind, multi-center study in 386 adult outpatients with DSM-IV GSAD. Patients were randomized to placebo, venlafaxine ER fixed low dose (75 mg/day), or venlafaxine ER flexible higher dose (150–225 mg/day). Primary efficacy variable was change on the Liebowitz Social Anxiety Scale (LSAS). Secondary efficacy variables included, among others, the proportion of responders on the CGI Global Improvement Item (score 1 or 2), and the proportion of remitters (defined as an LSAS score of ≤30).

Results

Improvement on the LSAS was greater with venlafaxine ER (at 75 mg/day or 150–225 mg/day) than placebo, and was sustained throughout the 6-month trial. Of patients receiving venlafaxine ER (at any dose), 58% responded to treatment compared to 33% of those receiving placebo (P<0.001); corresponding remission rates were 31% and 16% (P<0.01). There were no differences in outcome according to venlafaxine ER dosage.

Conclusions

Venlafaxine ER was effective in the treatment of GSAD. The comparable efficacy at low and higher doses may indicate that norepinephrine reuptake blockade does not contribute to therapeutic effect in GSAD. This hypothesis should be tested using agents with specific actions on norepinephrine reuptake blockade.

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References

  • Allgulander C, Hackett D, Salinas E (2001) Venlafaxine extended release (ER) in the treatment of generalised anxiety disorder. Br J Psychiatry 179:15–22

    Article  CAS  PubMed  Google Scholar 

  • Baldwin D, Bobes J, Stein DJ, Scharwachter I, Faure M (1999) Paroxetine in social phobia/social anxiety disorder—randomised, double-blind, placebo-controlled study. Br J Psychiatry 175:120–126

    CAS  PubMed  Google Scholar 

  • Ballenger JC, Davidson JRT, Lecrubier Y, Nutt DJ, Bobes J, Beidel DC, Ono Y, Westenberg HGM (1999) Consensus statement on social anxiety disorder from the international consensus group on depression and anxiety. J Clin Psychiatry 59:54–60

    Google Scholar 

  • Connor KM, Davidson JR, Churchill LE, Sherwood A, Foa EB, Weisler RH (2000) Psychometric properties of the Social Phobia Inventory (SPIN): a new self-rating scale. Br J Psychiatry 176:379–386

    Article  CAS  PubMed  Google Scholar 

  • Doyle AC, Pollack MH (2003) Establishment of remission criteria for anxiety disorders. J Clin Psychiatry 64:40–45

    Google Scholar 

  • Gelenberg AJ, Lydiard RB, Rudolph RL, Aguiar L, Haskins JT, 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

    Article  CAS  PubMed  Google Scholar 

  • Guy W (1976) ECDEU Assessment manual for psychopharmacology (revised). DHEW Publications (ADM), Rockville, Md., National Institute for Mental Health

  • Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62

    CAS  PubMed  Google Scholar 

  • Heimberg RG, Liebowitz MR, Hope DA, Schneier FR, Holt CS, Welkowitz LA, Juster HR, Campeas R, Bruch MA, Cloitre M, Fallon B, Klein DF (1998) Cognitive behavioral group therapy versus phenelzine therapy for social phobia. Arch Gen Psychiatry 55:1133–1141

    Article  CAS  PubMed  Google Scholar 

  • Heimberg RG, Horner KJ, Juster HR, Safren SA, Brown EJ, Schneier FR, Liebowitz MR (1999) Psychometric properties of the Liebowitz social anxiety scale. Psychol Med 29:199–212

    Article  CAS  PubMed  Google Scholar 

  • Issakidis C, Sanderson K, Corry J, Andrews G, Lapsley H (2004) Modelling the population cost-effectiveness of current and evidence-based optimal treatment for anxiety disorders. Psychol Med 34:19–35

    Article  CAS  PubMed  Google Scholar 

  • Kapczinski F, Lima MS, Souza JS, Schmitt R (2003) Antidepressants for generalized anxiety disorder. Cochrane Database Syst Rev CD003592

  • Katzelnick DJ, Kobak KA, DeLeire T, Henk HJ, Greist JH, Davidson JR, Schneier FR, Stein MB, Helstad CP (2001) Impact of generalized social anxiety disorder in managed care. Am J Psychiatry 158:1999–2007

    Article  CAS  PubMed  Google Scholar 

  • Kelsey JE (1995) Venlafaxine in social phobia. Psychopharmacol Bull 31:767–771

    CAS  PubMed  Google Scholar 

  • Kessler RC, Stein MB, Berglund PA (1998) Social phobia subtypes in the National Comorbidity Survey. Am J Psychiatry 155:613–619

    CAS  PubMed  Google Scholar 

  • Kessler RC, Stang P, Wittchen H-U, Stein MB, Walters EE (1999) Lifetime comorbidities between social phobia and mood disorders in the US National Comorbidity Survey. Psychol Med 29:555–567

    Article  CAS  PubMed  Google Scholar 

  • Kobak KA, Greist JH, Jefferson JW, Katzelnick DJ (2002) Fluoxetine in social phobia: a double-blind, placebo-controlled pilot study. J Clin Psychopharmacol 22:257–262

    Article  CAS  PubMed  Google Scholar 

  • Leon AC, Olfson M, Portera L, Farber L, Sheehan DV (1996) Assessing psychiatric impairment in primary care with the Sheehan Disability Scale. Psychopharmacol Bull 32:474

    Google Scholar 

  • Liebowitz MR, Schneier FR, Campeas R, Hollander E, Hatterer J, Fyer AJ, Gorman JM, Papp L, Davies S, Gully R, Klein DF (1992) Phenelzine versus atenolol in social phobia. Arch Gen Psychiatry 49:290–300

    CAS  PubMed  Google Scholar 

  • Liebowitz MR, Stein MB, Tancer ME, Carpenter D, Oakes R, Pitts CD (2002) A randomized, double-blind, fixed-dose comparison of paroxetine and placebo in the treament of generalized social anxiety disorder. J Clin Psychiatry 63:66–74

    CAS  PubMed  Google Scholar 

  • Liebowitz MR, DeMartinis NA, Weihs K, Londborg PD, Smith WT, Chung H, Fayyad R, Clary CM (2003) Efficacy of sertraline in severe generalized social anxiety disorder: results of a double-blind, placebo-controlled study. J Clin Psychiatry 64:785–792

    CAS  PubMed  Google Scholar 

  • Magee WJ, Eaton WW, Wittchen H-U, McGonagle KA, Kessler RC (1996) Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey. Arch Gen Psychiatry 53:159–168

    CAS  PubMed  Google Scholar 

  • Mendlowicz MV, Stein MB (2000) Quality of life in individuals with anxiety disorders. Am J Psychiatry 157:669–682

    Article  CAS  PubMed  Google Scholar 

  • Michelson D, Adler L, Spencer T, Reimherr FW, West SA, Allen AJ, Kelsey D, Wernicke J, Dietrich A, Milton D (2003) Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies. Biol Psychiatry 53:112–120

    Article  CAS  PubMed  Google Scholar 

  • Reilly MC, Zbrozek AS, Dukes EM (1993) The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics 4:353–365

    CAS  PubMed  Google Scholar 

  • Rickels K, Pollack MH, Sheehan D, Haskins JT (2000) Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder. Am J Psychiatry 157:968–974

    Article  CAS  PubMed  Google Scholar 

  • Schneier FR (2003) Social anxiety disorder. BMJ 327:515–516

    Article  PubMed  Google Scholar 

  • Schneier FR, Johnson J, Hornig CD, Liebowitz MR, Weissman MM (1992) Social phobia: comorbidity and morbidity in an epidemiological sample. Arch Gen Psychiatry 49:282–288

    CAS  PubMed  Google Scholar 

  • Schneier FR, Heckelman LR, Garfinkel R, Campeas R, Fallon BA, Gitow A, Street L, Del Bene D, Liebowitz MR (1994) Functional impairment in social phobia. J Clin Psychiatry 55:322–331

    CAS  PubMed  Google Scholar 

  • Seedat S, Stein MB (2004) Double-blind, placebo-controlled assessment of combined clonazepam with paroxetine compared with paroxetine monotherapy for generalized social anxiety disorder. J Clin Psychiatry 65:244–248

    CAS  PubMed  Google Scholar 

  • Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janaversus J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:22–33

    Google Scholar 

  • Solyom L, Ledwidge B, Solyom C (1986) Delineating social phobia. Br J Psychiatry 149:464–470

    CAS  PubMed  Google Scholar 

  • Stein MB, Gorman JM (2001) Unmasking social anxiety disorder. J Psychiatry Neurosci 26:185–189

    CAS  PubMed  Google Scholar 

  • Stein MB, Kean Y (2000) Disability and quality of life in social phobia. Am J Psychiatry 157:1606–1613

    Article  CAS  PubMed  Google Scholar 

  • Stein MB, Liebowitz MR, Lydiard RB, Bushnell W, Gergel IP (1998) Paroxetine treatment of generalized social anxiety disorder (social phobia): a randomized controlled trial. JAMA 280:708–713

    Article  CAS  Google Scholar 

  • Stein MB, Fyer AJ, Davidson JRT, Pollack MH, Wiita B (1999a) Fluvoxamine in social phobia (social anxiety disorder): a double-blind, placebo-controlled clinical study. Am J Psychiatry 156:756–760

    CAS  PubMed  Google Scholar 

  • Stein MB, McQuaid JR, Laffaye C, McCahill ME (1999b) Social phobia in the primary care medical setting. J Fam Pract 48:514–519

    CAS  PubMed  Google Scholar 

  • Stein MB, Torgrud LJ, Walker JR (2000) Social phobia symptoms, subtypes and severity: findings from a community survey. Arch Gen Psychiatry 57:1046–1052

    Article  CAS  PubMed  Google Scholar 

  • Stein MB, Fuetsch M, Muller N, Höfler M, Lieb R, Wittchen H-U (2001a) Social anxiety disorder and the risk of depression: a prospective community study of adolescents and young adults. Arch Gen Psychiatry 58:251–256

    Article  CAS  PubMed  Google Scholar 

  • Stein MB, Sareen J, Hami S, Chao J (2001b) Pindolol potentiation of paroxetine for generalized social phobia: a double-blind, placebo-controlled, crossover study. Am J Psychiatry 158:1727

    Google Scholar 

  • Stein DJ, Versiani M, Hair T, Kumar R (2002) Efficacy of paroxetine for relapse prevention in social anxiety disorder: a 24-week study. Arch Gen Psychiatry 59:1111–1118

    Article  CAS  PubMed  Google Scholar 

  • Stein MB, Sherbourne CD, Craske MG, Means-Christensen A, Bystritsky A, Katon W, Sullivan G, Roy-Byrne PP (2004) Quality of care for primary care patients with anxiety disorders. Am J Psychiatry (in press)

  • Thase ME, Rush AJ, Howland RH, Kornstein SG, Kocsis JH, Gelenberg AJ, Schatzberg AF, Koran LM, Keller MB, Russell JM, Hirschfeld RM, Lavange LM, Klein DN, Fawcett J, Harrison W (2002) Double-blind switch study of imipramine or sertraline treatment of antidepressant-resistant chronic depression. Arch Gen Psychiatry 59:233–239

    Article  CAS  PubMed  Google Scholar 

  • Van Ameringen M, Lane RM, Walker JR, Bowen RC, Chokka PR, Goldner EM, Johnston DG, Lavalle Y-J, Nandy S, Pecknold JC, Hadrava V, Swinson RP (2001) Sertraline treatment of generalized social phobia: a 20-week, double-blind, placebo-controlled study. Am J Psychiatry 158:275–281

    Article  PubMed  Google Scholar 

  • Walker JR, Van Ameringen MA, Swinson R, Bowen RC, Chokka PR, Goldner E, Johnston DC, Lavallie YJ, Nandy S, Pecknold JC, Hadrava V, Lane RM (2000) Prevention of relapse in generalized social phobia: results of a 24-week study in responders to 20 weeks of sertraline treatment. J Clin Psychopharmacol 20:636–644

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful to the investigators at the 19 sites who participated in this study (please see Appendix). Wyeth funded the study and supervised data collection and analyses. Drs. Stein, Pollack, and Kelsey are consultants to Wyeth, and Dr. Mangano is a Wyeth employee. Drs. Stein, Pollack, Bystritsky and Kelsey conduct clinical trials for and consult to numerous pharmaceutical companies.

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Authors and Affiliations

  1. Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0985, USA

    Murray B. Stein

  2. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA

    Mark H. Pollack

  3. Department of Psychiatry, University of California Los Angeles, Los Angeles, Calif., USA

    Alexander Bystritsky

  4. Georgia Institute of Mood and Anxiety Disorders, Atlanta, Ga., USA

    Jeffrey E. Kelsey

  5. USA Neuroscience Global Clinical Research and Development, Wyeth Research, Philadelphia, Penn., USA

    Richard M. Mangano

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  1. Murray B. Stein
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  2. Mark H. Pollack
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  4. Jeffrey E. Kelsey
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  5. Richard M. Mangano
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Corresponding author

Correspondence to Murray B. Stein.

Appendix 1: list of investigators

Appendix 1: list of investigators

The following investigators (in alphabetical order) participated at the sites shown: Jeffrey T. Apter MD, Stratford, N.J.; Alexander Byustritsky MD, Los Angeles, Calif.; Robert L. Dupont MD, Rockville, Md.; Steven M. Eisen MD, Philadelphia, Penn.; Naresh P. Emmanuel MD, Charleston, S.C.; Alan Feiger MD, Wheat Ridge, Col.; Jon F. Heiser MD, Newport Beach, Calif.; Jeffrey E. Kelsey MD, Atlanta, Ga.; Peter D. Londborg MD, Seattle, Wash.; James Lu, MD, Shreveport, La.; Concepcion B. Mendoza MD, Toms River, N.J.; Charles H. Merideth MD, San Diego, Calif.; Dennis Munjack MD, Beverly Hills, Calif.; Mark H. Pollack, Boston, Mass.; Elizabeth Reeve MD, St Paul, Minn.; Ward T. Smith MD, Portland, Ore.; Murray B. Stein MD, La Jolla, Calif.; Richard K. Templeton MD, Greenbelt, Md.; Harvey Tilker PhD, Paducah, Ken.

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Stein, M.B., Pollack, M.H., Bystritsky, A. et al. Efficacy of low and higher dose extended-release venlafaxine in generalized social anxiety disorder: a 6-month randomized controlled trial. Psychopharmacology 177, 280–288 (2005). https://doi.org/10.1007/s00213-004-1957-9

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  • DOI: https://doi.org/10.1007/s00213-004-1957-9

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