Original Article| Volume 62, ISSUE 10, P1149-1154, November 15, 2007

Download started.


A Randomized Controlled Trial of Venlafaxine ER Versus Placebo in Pediatric Social Anxiety Disorder


      Social anxiety disorder, which occurs in 2% to 5% of children and adolescents, is associated with significant distress and functional impairment.


      The objective of the randomized, masked controlled trial conducted in 48 academic and community centers in the United States was to evaluate the efficacy of venlafaxine ER in children and adolescents with generalized social anxiety disorder. A volunteer sample of 293 outpatients, age 8 to 17, who met diagnostic criteria for social anxiety disorder and were enrolled between February 2000 and March 2003 participated. Venlafaxine ER or placebo was titrated from a starting dose of 37.5 mg to a maximum dose of 225 mg over 16 weeks. The primary dependent measures were the Social Anxiety Scale, child or adolescent version (SAS-CA) and for responder analysis, a (dichotomized) Clinical Global Impressions-Improvement (CGI-I) score.


      Compared with placebo, intent-to-treat random regression analyses indicated a statistically significant advantage for venlafaxine ER (p = .001) on the SAS-CA. On the CGI-I responder analysis, 56% (95% confidence interval [CI], 47%-64%) of venlafaxine ER treated subjects responded, which was statistically superior to placebo (37% [95% CI, 29%-45%]). Three venlafaxine ER and no placebo patients developed treatment-emergent suicidality; there were no completed suicides.


      Venlafaxine ER is an effective and reasonably well-tolerated treatment for generalized social anxiety disorder in children and adolescents. As with other antidepressants, careful clinical monitoring for adverse events, including treatment-emergent suicidality, is essential.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Stein M.B.
        • Fuetsch M.
        • Muller N.
        • Hofler M.
        • Lieb R.
        • Wittchen H.U.
        Social anxiety disorder and the risk of depression: A prospective community study of adolescents and young adults.
        Arch Gen Psychiatry. 2001; 58: 251-256
        • Ollendick T.H.
        • March J.S.
        Phobic and Anxiety Disorders: A Clinician’s Guide to Effective Psychosocial and Pharmacological Interventions.
        Oxford University Press, London2004
        • Stein D.J.
        • Ipser J.C.
        • Balkom A.J.
        Pharmacotherapy for social phobia.
        Cochrane Database Syst Rev. 2004; 4 (CD001206)
        • Liebowitz M.R.
        • Gelenberg A.J.
        • Munjack D.
        Venlafaxine extended release vs placebo and paroxetine in social anxiety disorder.
        Arch Gen Psychiatry. 2005; 62: 190-198
        • Rickels K.
        • Mangano R.
        • Khan A.
        A double-blind, placebo-controlled study of a flexible dose of venlafaxine ER in adult outpatients with generalized social anxiety disorder.
        J Clin Psychopharmacol. 2004; 24: 488-496
        • Compton S.N.
        • Grant P.J.
        • Chrisman A.K.
        • Gammon P.J.
        • Brown V.L.
        • March J.S.
        Sertraline in children and adolescents with social anxiety disorder: An open trial.
        J Am Acad Child Adolesc Psychiatry. 2001; 40: 564-571
        • Birmaher B.
        • Axelson D.A.
        • Monk K.
        • Kalas C.
        • Clark D.B.
        • Ehmann M.
        • et al.
        Fluoxetine for the treatment of childhood anxiety disorders.
        J Am Acad Child Adolesc Psychiatry. 2003; 42: 415-423
        • Research Unit on Pediatric Psychopharmacology Anxiety Study Group
        Fluvoxamine for the treatment of anxiety disorders in children and adolescents.
        N Engl J Med. 2001; 344: 1279-1285
        • Wagner K.D.
        • Berard R.
        • Stein M.B.
        • Wetherhold E.
        • Carpenter D.J.
        • Perera P.
        • et al.
        A multicenter, randomized, double-blind, placebo-controlled trial of paroxetine in children and adolescents with social anxiety disorder.
        Arch Gen Psychiatry. 2004; 61: 1153-1162
        • Andrews J.M.
        • Ninan P.T.
        • Nemeroff C.B.
        Venlafaxine: A novel antidepressant that has a dual mechanism of action.
        Depression. 1996; 4: 48-56
        • Stahl S.M.
        • Grady M.M.
        • Moret C.
        • Briley M.
        SNRIs: Their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants.
        CNS Spectr. 2005; 10: 732-747
        • Weller E.B.
        • Weller R.A.
        • Davis G.P.
        Use of venlafaxine in children and adolescents: A review of current literature.
        Depress Anxiety. 2000; 12: 85-89
        • Whittington C.J.
        • Kendall T.
        • Fonagy P.
        • Cottrell D.
        • Cotgrove A.
        • Boddington E.
        Selective serotonin reuptake inhibitors in childhood depression: Systematic review of published versus unpublished data.
        Lancet. 2004; 363: 1341-1345
        • Silverman W.
        • Albano A.
        The Anxiety Disorders Interview Schedule for DSM-IV, Child and Parent Versions.
        The Psychological Corporation, San Antonio, TX1996
        • Brown E.G.
        • Wood L.
        • Wood S.
        The medical dictionary for regulatory activities (MedDRA).
        Drug Saf. 1999; 20: 109-117
        • Fisher L.
        • Dixon D.
        • Herson J.
        • Frankowski R.
        • Hearron M.
        • Peace K.
        Intention-to-treat in clinical trials.
        in: KE P. Statistical Issues in Drug Research and Development. Marcel Dekker, New York1990
        • Weinfert K.
        Repeated measures analyses: ANOVA, MANOVA, HLM.
        in: Grimm L. Yarnold P. Reading and Understanding More Multivariate Statistics. American Psychological Press, Washington, DC2000: 317-362
        • Gueorguieva R.
        • Krystal J.H.
        Move over ANOVA: Progress in analyzing repeated-measures data and its reflection in papers published in the Archives of General Psychiatry.
        Arch Gen Psychiatry. 2004; 61: 310-317
        • Brown H.
        • Prescott R.
        Applied Mixed Models in Medicine.
        John Wiley and Sons, New York1999
        • Rosenthal R.
        • Rosnow R.
        • Rubin D.B.
        Contrasts and Effect Sizes in Behavioral Research.
        Cambridge University Press, Cambridge, England2000
        • Sackett D.
        • Richardson W.
        • Rosenberg W.
        • Haynes B.
        Evidence-Based Medicine.
        2nd ed. Churchill Livingstone, London2000
        • Hammad T.A.
        • Laughren T.P.
        • Racoosin J.A.
        Suicide rates in short-term randomized controlled trials of newer antidepressants.
        J Clin Psychopharmacol. 2006; 26: 203-207
        • Hammad T.A.
        • Laughren T.
        • Racoosin J.
        Suicidality in pediatric patients treated with antidepressant drugs.
        Arch Gen Psychiatry. 2006; 63: 332-339
        • Ginsburg G.S.
        • Grover R.L.
        Assessing and treating social phobia in children and adolescents.
        Pediatr Ann. 2005; 34: 119-127
        • March J.S.
        Combining medication and psychosocial treatments: An evidence-based medicine approach.
        International Review of Psychiatry. 2002; 14: 155-163