Initial severity and antidepressant efficacy for anxiety disorders, obsessive-compulsive disorder, and posttraumatic stress disorder: An individual patient data meta-analysis

Ymkje Anna de Vries, Annelieke M Roest, Johannes G M Burgerhof, Peter de Jonge, Ymkje Anna de Vries, Annelieke M Roest, Johannes G M Burgerhof, Peter de Jonge

Abstract

Background: It has been suggested that antidepressant benefits are smaller for mild than severe depression. Because antidepressants are also used for anxiety disorders, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD), we examined the influence of severity for these disorders.

Methods: We used individual patient data of eight trials (3,430 participants) for generalized anxiety disorder (GAD); four trials (1,195 participants) for social anxiety disorder (SAD); four trials (1,132 participants) for OCD; three trials (1,071 participants) for PTSD; and 10 trials (2,151 participants) for panic disorder (PD). Mixed-effects models were used to investigate an interaction between severity and treatment group.

Results: For GAD and PD, severity moderated antidepressant efficacy. The antidepressant-placebo difference was 1.4 (95% CI: 0.4-2.5; SMD: 0.21) Hamilton Anxiety Rating Scale (HAM-A) points for participants with mild GAD (baseline HAM-A = 10), increasing to 4.0 (3.4-4.6; SMD: 0.45) or greater for severely ill participants (HAM-A ≥ 30). For PD, the difference was 0.4 (0.3-0.6) panic attacks/2 weeks for participants with 10 panic attacks/2 weeks at baseline, increasing to 4.7 (3.0-6.4) for participants with 40. For SAD, OCD, and PTSD, no interaction was found. Across severity levels, the differences were 16.1 (12.9-19.3; SMD: 0.59) Liebowitz Social Anxiety Scale points, 3.4 (2.5-4.4, SMD: 0.39) Yale-Brown Obsessive-Compulsive Scale points, and 10.3 (6.9-13.6; SMD: 0.41) Clinician-Administered PTSD Scale points.

Conclusions: Antidepressants are equally effective across severity levels for SAD, OCD, and PTSD. For GAD and PD, however, benefits are small at low severity, and the benefit-risk ratio may be unfavorable for these patients.

Trial registration: ClinicalTrials.gov NCT02476136.

Keywords: antidepressive agents; anxiety disorders; meta-analysis; obsessive-compulsive disorder; panic disorder; posttraumatic stress disorder.

Conflict of interest statement

All authors have declared that they have no conflict of interest.

© 2018 Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
Predicted change from baseline for antidepressant‐ and placebo‐treated participants with (a) generalized anxiety disorder, (b) social anxiety disorder, (c) obsessive‐compulsive disorder, and (d) PTSD. Predictions are derived from the full model, including nonsignificant interaction terms. Data points were jittered to reduce over‐plotting
Figure 2
Figure 2
Predicted numbers of panic attacks/2 weeks at endpoint for antidepressant‐ and placebo‐treated participants with panic disorder. Predictions are derived from the full model, including nonsignificant interaction terms. Data points were jittered to reduce over‐plotting

References

    1. Ackerman, D. L. , & Greenland, S. (2002). Multivariate meta‐analysis of controlled drug studies for obsessive‐compulsive disorder. Journal of Clinical Psychopharmacology, 22(3), 309–317.
    1. Altman, D. G. , & Royston, P. (2006). The cost of dichotomising continuous variables. British Medical Journal, 332(7549), 1080–1080. 10.1136/bmj.332.7549.1080
    1. Bandelow, B. , Reitt, M. , Röver, C. , Michaelis, S. , Görlich, Y. , & Wedekind, D. (2015). Efficacy of treatments for anxiety disorders: A meta‐analysis. International Clinical Psychopharmacology, 30(4), 183–192. 10.1097/YIC.0000000000000078
    1. Curtiss, J. , Andrews, L. , Davis, M. , Smits, J. , & Hofmann, S. G. (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. 10.1080/14656566.2017.1285907
    1. Davis, M. L. , Smits, J. A. , & Hofmann, S. G. (2014). Update on the efficacy of pharmacotherapy for social anxiety disorder: A meta‐analysis. Expert Opinion on Pharmacotherapy, 15(16), 2281–2291. 10.1517/14656566.2014.955472
    1. de Vries, Y. A. , de Jonge, P. , van den Heuvel, E. , Turner, E. H. , & Roest, A. M. (2016). Influence of baseline severity on antidepressant efficacy for anxiety disorders: Meta‐analysis and meta‐regression. British Journal of Psychiatry, 208(6), 515–521. 10.1192/bjp.bp.115.173450
    1. Fournier, J. C. , Derubeis, R. J. , Hollon, S. D. , Dimidjian, S. , Amsterdam, J. D. , Shelton, R. C. , & Fawcett, J. (2010). Antidepressant drug effects and depression severity. Journal of the American Medical Association, 303(1), 47–53.
    1. Gibbons, R. D. , Hur, K. , Brown, C. H. , Davis, J. M. , & Mann, J. J. (2012). Benefits from antidepressants: Synthesis of 6‐week patient‐level outcomes from double‐blind placebo‐controlled randomized trials of fluoxetine and venlafaxine. Archives of General Psychiatry, 69(6), 572–579. 10.1001/archgenpsychiatry.2011.2044
    1. Kessler, R. C. , Chiu, W. T. , Demler, O. , & Walters, E. E. (2005). Prevalence, severity, and comorbidity of 12‐month DSM‐IV disorders in the national comorbidity survey replication. Archives of General Psychiatry, 62, 617–627.
    1. Khan, A. , Bhat, A. , Faucett, J. , Kolts, R. L. , & Brown, W. A. (2011). Antidepressant‐placebo differences in 16 clinical trials over 10 years at a single site: Role of baseline severity. Psychopharmacology, 214(4), 961–965. 10.1007/s00213-010-2107-1
    1. Khan, A. , Brodhead, A. E. , Kolts, R. L. , & Brown, W. A. (2005). Severity of depressive symptoms and response to antidepressants and placebo in antidepressant trials. Journal of Psychiatric Research, 39(2), 145–150. 10.1016/j.jpsychires.2004.06.005
    1. Khan, A. , Leventhal, R. M. , Khan, S. R. F. , & Brown, W. A. (2002). Severity of depression and response to antidepressants and placebo: An analysis of the Food and Drug Administration database. Journal of Clinical Psychopharmacology, 22(1), 40–45.
    1. Kirsch, I. , Deacon, B. J. , Huedo‐Medina, T. B. , Scoboria, A. , Moore, T. J. , & Johnson, B. T. (2008). Initial severity and antidepressant benefits: A meta‐analysis of data submitted to the food and drug administration. PLoS Medicine, 5(2), e45 10.1371/journal.pmed.0050045
    1. Kraemer, H. , Morgan, G. A. , Leech, N. , Gliner, J. A. , Vaske, J. J. , & Harmon, R. J. (2003). Measures of clinical significance. The American Academy of Child and Adolescent Psychiatry, 42(12), 1524–1529. 10.1097/01.chi.0000091507.46853.d1
    1. Krueger, R. F. (1999). The structure of common mental disorders. Archives of General Psychiatry, 56(10), 921–926. 10.1001/archpsyc.56.10.921
    1. Montgomery, S. A. (1998). Implications of the severity of social phobia. Journal of Affective Disorders, 50 (Suppl 1), S17–S22.
    1. Montgomery, S. A. , McIntyre, A. , Osterheider, M. , Sarteschi, P. , Zitterl, W. , Zohar, J. , … Wood, A. J. (1993). A double‐blind, placebo‐controlled study of fluoxetine in patients with DSM‐III‐R obsessive‐compulsive disorder. The Lilly European OCD Study Group. European Neuropsychopharmacology, 3(2), 143–152.
    1. Montgomery, S. A. , Sheehan, D. V. , Meoni, P. , Haudiquet, V. , & Hackett, D. (2002). Characterization of the longitudinal course of improvement in generalized anxiety disorder during long‐term treatment with venlafaxine XR. Journal of Psychiatric Research, 36(4), 209–217. Retrieved from
    1. National Institute for Health and Care Excellence . (2009). Depression in adults: The treatment and management of depression in adults (CG90), London: Author.
    1. Oehrberg, S. , Christiansen, P. E. , Behnke, K. , Borup, A. L. , Severin, B. , Soegaard, J. , … Manniche, P. M. (1995). Paroxetine in the treatment of panic disorder. A randomised, double‐blind, placebo‐controlled study. British Journal of Psychiatry, 167, 374–379. 10.1192/bjp.167.3.374
    1. Pae, C.‐U. , Wang, S.‐M. , Han, C. , Lee, S.‐J. , Patkar, A. A. , Masand, P. S. , & Serretti, A. (2015). Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: A systematic review and meta‐analysis. Journal of Psychiatric Research, 64, 88–98. 10.1016/j.jpsychires.2015.02.017
    1. Pollack, M. H. , Meoni, P. , Otto, M. W. , Simon, N. , & Hackett, D. (2003). Predictors of outcome following venlafaxine extended‐release treatment of DSM‐IV generalized anxiety disorder: A pooled analysis of short‐ and long‐term studies. Journal of Clinical Psychopharmacology, 23(3), 250–259. 10.1097/01.jcp.0000084025.22282.84
    1. Qaseem, A. , Barry, M. J. , & Kansagara, D. (2016). Nonpharmacologic versus pharmacologic treatment of adult patients with major depressive disorder: A clinical practice guideline from the American College of Physicians. Annals of Internal Medicine, 164, 350–359. 10.7326/M15-2570
    1. Rabinowitz, J. , Werbeloff, N. , Mandel, F. S. , Menard, F. , Marangell, L. , & Kapur, S. (2016). Initial depression severity and response to antidepressants v. placebo: Patient‐level data analysis from 34 randomised controlled trials. The British Journal of Psychiatry, 209(5), 427–428. 10.1192/bjp.bp.115.173906
    1. Roest, A. M. , de Jonge, P. , Williams, C. D. , de Vries, Y. A. , Schoevers, R. A. , & Turner, E. H. (2015). Reporting bias in clinical trials investigating the efficacy of second‐generation antidepressants in the treatment of anxiety disorders: A report of 2 meta‐analyses. JAMA Psychiatry, 72(5), 500–510. 10.1001/jamapsychiatry.2015.15
    1. Rollman, B. L. , Belnap, B. H. , Mazumdar, S. , Zhu, F. , Kroenke, K. , Schulberg, H. C. , & Katherine Shear, M. (2005). Symptomatic severity of PRIME‐MD diagnosed episodes of panic and generalized anxiety disorder in primary care. Journal of General Internal Medicine, 20(7), 623–628. 10.1111/j.1525-1497.2005.0120.x
    1. Shear, M. K. , Brown, T. A. , Barlow, D. H. , Money, R. , Sholomskas, D. E. , Woods, S. W. , … Papp, L. A. (1997). Multicenter collaborative panic disorder severity scale. American Journal of Psychiatry, 154, 1571–1575.
    1. Soomro, G. M. , Altman, D. G. , Rajagopal, S. , & Oakley Browne, M. (2008). Selective serotonin re‐uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD). Cochrane Database of Systematic Reviews, 1, CD001765.
    1. Spijker, J. , Bockting, C. L. H. , Meeuwissen, J. A. C. , van Vliet, I. M. , Emmelkamp, P. M. G. , Hermens, M. L. M. , & van Balkom, A. J. L. M. (2013). Multidisciplinaire richtlijn depressie (3e revisie), Utrecht: Trimbos‐instituut.
    1. Stein, D. J. , Ipser, J. C. , & Seedat, S. (2006). Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database of Systematic Reviews, 1, CD002795.
    1. Stein, D. J. , Kasper, S. , Andersen, E. W. , Nil, R. , & Lader, M. (2004). Escitalopram in the treatment of social anxiety disorder: Analysis of efficacy for different clinical subgroups and symptom dimensions. Depression and Anxiety, 20(4), 175–181. 10.1002/da.20043
    1. Stein, D. J. , Stein, M. B. , Goodwin, W. , Kumar, R. , & Hunter, B. (2001). The selective serotonin reuptake inhibitor paroxetine is effective in more generalized and in less generalized social anxiety disorder. Psychopharmacology, 158(3), 267–272. 10.1007/s002130100880
    1. Sugarman, M. A. , Loree, A. M. , Baltes, B. B. , Grekin, E. R. , & Kirsch, I. (2014). The efficacy of paroxetine and placebo in treating anxiety and depression: A meta‐analysis of change on the Hamilton rating scales. PLoS One, 9(8), e106337 10.1371/journal.pone.0106337
    1. Thompson, S. G. , & Higgins, J. P. T. (2002). How should meta‐regression analyses be undertaken and interpreted? Statistics in Medicine, 21(11), 1559–1573. 10.1002/sim.1187
    1. Wong, J. , Motulsky, A. , Eguale, T. , Buckeridge, D. L. , Abrahamowicz, M. , & Tamblyn, R. (2016). Treatment indications for antidepressants prescribed in primary care in Quebec, Canada, 2006–2015. Journal of the American Medical Association, 315(20), 2230–2231.

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