Hostname: page-component-8448b6f56d-mp689 Total loading time: 0 Render date: 2024-04-15T19:08:33.470Z Has data issue: false hasContentIssue false
  • English
  • Français

Pharmacological treatments for social anxiety disorder in adults: a systematic review and network meta-analysis

Published online by Cambridge University Press:  10 February 2020

Taryn Williams Open the ORCID record for Taryn Williams [Opens in a new window] ,
Michael McCaul ,
Guido Schwarzer ,
Andrea Cipriani ,
Dan J Stein  and
Jonathan Ipser
Taryn Williams*
Affiliation:
Department of Psychiatry and Neuroscience Institute, University of Cape Town, South Africa
Michael McCaul
Affiliation:
Biostatistics Unit, Division of Epidemiology and Biostatistics, Department of Global Health, Universiteit Stellenbosch University, Cape Town, South Africa
Guido Schwarzer
Affiliation:
Institute of Medical Biometry and Statistics Faculty of Medicine and Medical Center, University of Freiburg, Germany
Andrea Cipriani
Affiliation:
Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK
Dan J Stein
Affiliation:
Department of Psychiatry and Neuroscience Institute, University of Cape Town, South Africa SA MRC Unit on Risk & Resilience in Mental Disorders
Jonathan Ipser
Affiliation:
Department of Psychiatry and Neuroscience Institute, University of Cape Town, South Africa
*
Author for correspondence: Taryn Williams, Email: tarynamos@gmail.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

The aim of this paper was to provide a systematic review and update on the pharmacotherapy of social anxiety disorder (SAD), including the efficacy and tolerability of these agents, the ranking of interventions, and the grading of results by quality of evidence.

Methods:

The Common Mental Disorder Controlled Trial Register and two trial registries were searched for randomised controlled trials (RCTs) comparing any pharmacological intervention or placebo in the treatment of SAD. We performed a standard pairwise meta-analysis using a random effects model and carried out a network meta-analysis (NMA) using the statistical package, R. Quality of evidence was also assessed.

Results:

We included 67 RCTs in the review and 21 to 45 interventions in the NMA. Paroxetine was most effective in the reduction of symptom severity as compared to placebo. Superior response to treatment was also observed for paroxetine, brofaromine, bromazepam, clonazepam, escitalopram, fluvoxamine, phenelzine, and sertraline. Higher dropout rates were found for fluvoxamine. Brofaromine, escitalopram, fluvoxamine, paroxetine, pregabalin, sertraline, and venlafaxine performed worse in comparison to placebo for the outcome of dropouts due to adverse events. Olanzapine yielded a relatively high rank for treatment efficacy and buspirone the worse rank for dropouts due to any cause.

Conclusion:

The differences between drugs and placebo were small, apart from a significant reduction in symptom severity and response for paroxetine. We suggest paroxetine as a first-line treatment of SAD, with the consideration of future research on the drug olanzapine as well as brofaromine, bromazepam, clonazepam, escitalopram, fluvoxamine, phenelzine, and sertraline because we observed a response to treatment.

Keywords

network meta-analysissocial anxiety disordersystematic review
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 32 , Issue 4 , August 2020 , pp. 169 - 176
Copyright
© Scandinavian College of Neuropsychopharmacology 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aarre, TF (2003) Phenelzine efficacy in refractory social anxiety disorder: a case series. Nordic Journal of Psychiatry 57(4), 313–315.CrossRefGoogle ScholarPubMed
American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders, 5th Edn. Washington, DC: American Psychiatric Association Publishing.Google Scholar
Ballenger, JC, Davidson, JR, Lecrubier, Y, Nutt, DJ, Bobes, J, Beidel, DC, Ono, Y and Westenberg, HG (1998) Consensus statement on social anxiety disorder from the international consensus group on depression and anxiety. The Journal of Clinical Psychiatry 59(17), 54–60.Google Scholar
Bandelow, B, Zohar, J, Hollander, E, Kasper, S and Moller, HJ (2002) WFSBP Task Force on Treatment Guidelines for Anxiety O-CaPSD. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders. The World Journal of Biological Psychiatry 3(4), 171–199.CrossRefGoogle ScholarPubMed
Bandelow, B, Sher, L, Bunevicius, R, Hollander, E, Kasper, S, Zohar, J, Möller, HJ, WFSBP Task Force on Mental Disorders in Primary Care & WFSBP Task Force on Anxiety Disorders, OCD and PTSD (2012) Guidelines for the pharmacological treatment of anxiety disorders, obsessive - compulsive disorder and posttraumatic stress disorder in primary care. International Journal of Psychiatry in Clinical Practice 16, 77–84.CrossRefGoogle ScholarPubMed
Bandelow, B and Michaelis, S (2015) Epidemiology of anxiety disorders in the 21st century. Dialogues in Clinical Neuroscience 17(3), 327–335.Google ScholarPubMed
Brignardello-Petersen, R, Bonner, A, Alexander, P, Siemieniuk, R, Furukawa, TA, Rochwerg, B, Hazlewood, GS, Alhazzani, W, Mustafa, RA, Murad, MH, Puhan, MA, Schünemann, HJ, Guyatt, GH and GRADE Working Group (2017) Advances in the GRADE approach to rate the certainty in estimates from a network meta-analysis. Journal of Clinical Epidemiology, 93, 36–44.CrossRefGoogle ScholarPubMed
Blanco, C, Schneier, FR, Schmidt, A, Blanco-Jerez, C, Marshall, RD, Sanchez-Lacay, A and Liebowitz, MR (2003) Pharmalogical treatment of social anxiety disorder: a meta-analysis. Depression and Anxiety 18(1), 29–40.CrossRefGoogle Scholar
Blanco, C, Bragdon, LB, Schneier, FR and Liebowitz, MR (2013) The evidence-based pharmacotherapy of social anxiety disorder. The International Journal of Neuropsychopharmacology 16(1), 235–249.CrossRefGoogle ScholarPubMed
Chaimani, A, Mavridis, D and Salanti, G (2014) A hands-on practical tutorial on performing meta analysis with Stata. Evidence-Based Mental Health 17, 111–116.CrossRefGoogle ScholarPubMed
Cohen, JN, Drabick, DAG and Heimberg, RG (2017) Pharmacotherapy for Social Anxiety Disorder: Interpersonal Predictors of Outcome and the Mediating Role of the Working Alliance. Journal of Anxiety Disorders 52, 79–87.CrossRefGoogle ScholarPubMed
Cuijpers, P, Sijbrandij, M, Koole, SL, Andersson, G, Beekman, AT and Reynolds, CF (2013) The efficacy of psychotherapy and pharmacotherapy in treating depressive and anxiety disorders: a meta-analysis of direct comparisons. World Psychiatry 12(2), 137–148.CrossRefGoogle ScholarPubMed
Curtiss, J, Andrews, L, Davis, M, Smits, J and Hofmann, SG (2017) A meta-analysis of pharmacotherapy for social anxiety disorder: an examination of efficacy, moderators, and mediators. Expert Opinion on Pharmacotherapy 18(3), 243–251.CrossRefGoogle Scholar
Del Re, AC, Spielmans, GI, Flückiger, C and Wampold, BE (2014) Efficacy of new generation antidepressants: differences seem illusory. PLoS One 8, pe63509.CrossRefGoogle ScholarPubMed
De Menezes, GB, Coutinho, ESF, Fontenelle, LF, Vigne, P, Figueira, I and Versiani, MÁ (2011) Second-generation antidepressants in social anxiety disorder: meta-analysis of controlled clinical trials. Psychopharmacology 215(1), 1–11.CrossRefGoogle ScholarPubMed
Efthimiou, O, Debray, TPA, van Valkenhoef, G, Trelle, S, Panayidou, K, Moons, KG, Reitsma, JB, Shang, A, Salanti, G and GetReal Methods Review Group (2016) GetReal in network meta-analysis: a review of the methodology. Research Synthesis Methods, 1–29.Google ScholarPubMed
Guyatt, G, Oxman, AD, Akl, EA, Kunz, R, Vist, G and Brozek, J (2011) GRADE guidelines: Introduction-GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 64(4), 383–394.CrossRefGoogle ScholarPubMed
Guy, W (1976) ECDEU Assessment Manual for Psychopharmacology, Washington, DC: US National Institute of Health.Google Scholar
Hansen, RA, Gaynes, BN, Gartlehner, G, Moore, CG, Tiwari, R and Lohr, KN (2008) Efficacy and tolerability of second-generation antidepressants in social anxiety disorder. International Clinical Psychopharmacology 23, 170–179.CrossRefGoogle ScholarPubMed
Heimberg, RG, Hofmann, SG, Liebowitz, MR, Schneier, FR, Smits, JAJ, Stein, MB, Hinton, DE and Craske, MG (2014) Social anxiety disorder in DSM-5. Depression and Anxiety 31, 472–479.CrossRefGoogle ScholarPubMed
Higgins, JP and Green, S (2011) Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, viewed September 2011, www.cochrane-handbook.org.Google Scholar
Ipser, JC, Sander, C, Seifan, A and Stein, DJ (2009) Augmentation of psychotherapy with d-cycloserine for anxiety disorders. Cochrane Database of Systematic Reviews(2).CrossRefGoogle Scholar
Jackson, D, White, IR and Riley, RD (2012) Quantifying the impact of between-study heterogeneity in multivariate meta-analyses. Statistics in Medicine 31(29), 3805–3820.CrossRefGoogle ScholarPubMed
Kessler, RC, Berglund, P, Demler, O, Jin, R, Merikangas, KR and Walters, EE (2005) Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62(6), 593–602.CrossRefGoogle ScholarPubMed
Kelsey, JE (1995) Venlafaxine in social phobia. Psychopharmacology Bulletin 31(4), 767–771.Google ScholarPubMed
Liebowitz, MR (1987) Social Phobia. Modern Problems in Pharmacopsychiatry 22, 141–173.CrossRefGoogle ScholarPubMed
Liu, X, Li, X, Zhang, C, Sun, M, Sun, S, Xu, Y and Tian, X (2018) Efficacy and tolerability of fluvoxamine in adults with social anxiety disorder. A meta-analysis. Medicine 97(28), pe11547.CrossRefGoogle ScholarPubMed
Mavridis, D, Giannatsi, M, Cipriani, A and Salanti, G (2015) A primer on network meta-analysis with emphasis on mental health. Evidence Based Mental Health 18(2), 40–46.CrossRefGoogle ScholarPubMed
Mayo-Wilson, E, Dias, S, Mavranezouli, I, Kew, K, Clark, DM, Ades, AE and Stephen, P (2014) Psychological and pharmacological interventions for social anxiety disorder in adults: a systematic review and network meta-analysis. Lancet Psychiatry 1, 368–376.CrossRefGoogle ScholarPubMed
National Institute for Health and Care Excellence (2011) Common mental health problems: identification and pathways to care. NICE Clinical Guideline, viewed 6 March 2013, www.nice.org.uk.Google Scholar
National Institute for Health and Care Excellence (2013) Social anxiety disorder: recognition, assessment and treatment. NICE Clinical Guideline, viewed 5 January 2016, www.nice.org.uk.Google Scholar
Pecknold, JC, McClure, DJ, Appeltauer, L, Allan, T and Wrzesinski, L (1982) Does tryptophan potentiate clomipramine in the treatment of agoraphobic and agoraphobic and social phobic patients. British Journal of Psychiatry 140, 484–490.CrossRefGoogle ScholarPubMed
Puhan, MA, Schünemann, HJ, Murad, MH, Li, T, Brignardello-Petersen, R, Singh, JA, Kessels, AG, Guyatt, GH and GRADE Working Group (2014) A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis. British Medical Journal 349, 5630.CrossRefGoogle Scholar
Rücker, G and Schwarzer, G (2015) Ranking treatments in frequentist network meta-analysis works without resampling methods. BMC Medical Research Methodology 15(1), 58.CrossRefGoogle ScholarPubMed
Rücker, G and Schwarzer, G (2018) Network meta-analysis of combinations of treatments. Manuscript, submitted.Google Scholar
Salanti, G, Ades, AE and Ioannidis, JP (2011) Graphical methods and numerical summaries for presenting results from multiple-treatment meta analysis: an overview and tutorial. Journal of Clinical Epidemiology 64, 163–171.CrossRefGoogle ScholarPubMed
Salanti, G (2012) Indirect and mixed-treatment comparison, network, or multiple treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool. Research Synthesis Methods 3, 80–97.CrossRefGoogle ScholarPubMed
Schardt, C, Adams, MB, Owens, T, Keitz, S and Fontelo, P (2014) Utilization of the PICO framework to improve searching PubMed for clinical questions. BMC Medical Informatics and Decision Making 7(1), 16.CrossRefGoogle Scholar
Schwarzer, G (2007) meta: An R package for meta-analysis. R News 7(3), 40–45.Google Scholar
Stein, MB, Sareen, J, Hami, S and Chao, J (2001) Pindolol potentiation of paroxetine for generalized social phobia: a double-blind, placebo-controlled, crossover study. The American Journal of Psychiatry 158(10), 1725–1727.CrossRefGoogle ScholarPubMed
Stein, MB and Stein, DJ (2008) Social anxiety disorder. Lancet 271(9618), 1115–1125.CrossRefGoogle Scholar
Stein, DJ, Lim, CCW, Roest, AM, de Jonge, , P, Aguilar-Gaxiola, S and Al-Hamzawi, A (2017) The cross-national epidemiology of social anxiety disorder: Data from the World Mental Health Survey Initiative. BMC Medicine 15(143), 1–21.CrossRefGoogle ScholarPubMed
Van Ameringen, M, Mancini, C and Wilson, C (1996) Buspirone augmentation of selective serotonin reuptake inhibitors (SSRIs) in social phobia. Journal of Affective Disorders 39(2), 115–121.CrossRefGoogle Scholar
Van der Linden, GJ, Stein, DJ and van Balkom, AJ (2000) The efficacy of the selective serotonin reuptake inhibitors for social anxiety disorder (social phobia): a meta-analysis of randomized controlled trials. International Clinical Psychopharmacology 15(2), 15–24.CrossRefGoogle ScholarPubMed
Williams, T, Hattingh, CJ, Kariuki, CM, Tromp, SA, van Balkom, , AJ, Ipser, JC and Stein, DJ (2017) Pharmacotherapy for social anxiety disorder (SAnD). Cochrane Database of Systematic Reviews (10. Art. No.: CD001206).CrossRefGoogle Scholar
Wood, L, Egger, M, Gluud, LL, Schulz, KF, Jüni, P, Altman, DG, Gluud, C, Martin, RM, Wood, AJG and Sterne, JAC (2008) Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. British Medical Journal 336, 601–605.CrossRefGoogle ScholarPubMed
World Health Organisation (WHO ) (2013) Pharmacological treatment of mental disorders in primary health care, WHO Library Cataloguing-in-Publication Data), 1–82.Google Scholar
Supplementary material: File

Williams et al. supplementary material

Williams et al. supplementary material

Download Williams et al. supplementary material(File)
File 3.4 MB