Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-09T14:08:48.803Z Has data issue: false hasContentIssue false
  • English
  • Français

The Effects of Blinding on the Outcomes of Psychotherapy and Pharmacotherapy for Adult Depression: a Meta-Analysis

Published online by Cambridge University Press:  11 July 2015

P. Cuijpers ,
E. Karyotaki ,
G. Andersson ,
J. Li ,
R. Mergl  and
U. Hegerl
P. Cuijpers*
Affiliation:
Department of clinical psychology, VU University Amsterdam, 1, Van der Boechorststraat, 1081BT Amsterdam, The Netherlands EMGO Institute for Health and Care Research, The Netherlands
E. Karyotaki
Affiliation:
Department of clinical psychology, VU University Amsterdam, 1, Van der Boechorststraat, 1081BT Amsterdam, The Netherlands EMGO Institute for Health and Care Research, The Netherlands
G. Andersson
Affiliation:
Department of behavioural sciences and learning, Swedish institute for disability research, Linköping University, Sweden Department of clinical neuroscience, psychiatry section, Karolinska Institutet, Stockholm, Sweden
J. Li
Affiliation:
Key laboratory of mental health, institute of psychology, Chinese academy of sciences, Beijing, China
R. Mergl
Affiliation:
Department of psychiatry and psychotherapy, university of Leipzig, Leipzig, Germany
U. Hegerl
Affiliation:
Department of psychiatry and psychotherapy, university of Leipzig, Leipzig, Germany
*
*Corresponding author. Department of Clinical Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands. Tel.: +31 20 5988757; fax: +31 20 5988758. E-mail address: [email protected] (P. Cuijpers).
Get access

Abstract

Background

Randomized trials with antidepressants are often run under double blind placebo-controlled conditions, whereas those with psychotherapies are mostly unblinded. This can introduce bias in favor of psychotherapy when the treatments are directly compared. In this meta-analysis, we examine this potential source of bias.

Methods

We searched Pubmed, PsycInfo, Embase and the Cochrane database (1966 to January 2014) by combining terms indicative of psychological treatment and depression, and limited to randomized trials. We included 35 trials (with 3721 patients) in which psychotherapy and pharmacotherapy for adult depression were directly compared with each other. We calculated effect sizes for each study indicating the difference between psychotherapy and pharmacotherapy at post-test. Then, we examined the difference between studies with a placebo condition and those without in moderator analyses.

Results

We did not find a significant difference between the studies with and those without a placebo condition. The studies in which a placebo condition was included indicated no significant difference between psychotherapy and pharmacotherapy (g = −0.07; NNT = 25). Studies in which no placebo condition was included (and patients and clinicians in both conditions were not blinded), resulted in a small, but significant difference between psychotherapy and pharmacotherapy in favor of pharmacotherapy (g = −0.13; NNT = 14).

Conclusions

Studies comparing psychotherapy and pharmacotherapy in which both groups of patients (and therapists) are not blinded (no placebo condition is included) result in a very small, but significantly higher effect for pharmacotherapy.

Keywords

Major depressionPsychotherapyPharmacotherapyMeta-analysisCognitive-behavior therapy
Type
Review
Information
European Psychiatry , Volume 30 , Issue 6 , September 2015 , pp. 685 - 693
Copyright
Copyright © Elsevier Masson SAS 2015

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

Adli, M., Hegerl, U.Do we underestimate the benefits of antidepressants. Lancet 2014;383:1361–1362.CrossRefGoogle ScholarPubMed
Barber, J., Barrett, M.S., Gallop, R., Rynn, M.A., Rickels, K.Short-term dynamic psychotherapy versus pharmacotherapy for major depressive disorder: a randomized, placebo-controlled trial. J Clin Psychiatry 2012;73:66–73.CrossRefGoogle ScholarPubMed
Barrett, J.E., Williams, J.W., Oxman, T.E., Frank, E., Katon, W., Sullivan, M., et al.Treatment of dysthymia and minor depression in primary care: a randomized trial in patients aged 18 to 59 years. J Fam Pract 2001;50:405–412.Google ScholarPubMed
Bedi, N., Chilvers, C., Churchill, R., Dewey, M., Duggan, C., Fielding, K., et al.Assessing effectiveness of treatment of depression in primary care. Partially randomised preference trial. Br J Psychiatr 2000;177:312–318.CrossRefGoogle ScholarPubMed
Blackburn, I.M., Bishop, S., Glen, A.I., Whalley, L.J., Christie, J.E.The efficacy of cognitive therapy in depression: a treatment trial using cognitive therapy and pharmacotherapy, each alone and in combination. Br J Psychiatry 1981;139:181–189.CrossRefGoogle ScholarPubMed
Blackburn, I.M., Moore, R.G.Controlled acute and follow-up trial of cognitive therapy and pharmacotherapy in out-patients with current depression. Br J Psychiatry 1997;171:328–334.CrossRefGoogle Scholar
Borenstein, M., Hedges, L.V., Higgins, J.P.T., Rothstein, H.R.Introduction to meta-analysis. Chichester, UK: Wiley; 2009.CrossRefGoogle Scholar
Browne, G., Steiner, M., Roberts, J., Gafni, A., Byrne, C., Dunn, E., et al.Sertraline and/or interpersonal psychotherapy for patients with dysthymic disorder in primary care: 6-month comparison with longitudinal 2-year follow-up of effectiveness and costs. J Affect Dis 2002;68:317–330.CrossRefGoogle ScholarPubMed
Cohen, J.Statistical power analysis for the behavioral sciences 2nd ed.Hillsdale, NJ: Erlbaum; 1988.Google Scholar
Cuijpers, P., Hollon, S.D., van Straten, A., Bockting, C., Berking, M., Andersson, G.Does cognitive behaviour therapy have an enduring effect that is superior to keeping patients on continuation pharmacotherapy?. A meta-analysis. BMJ Open 2013. 3. http://dx.doi.org/10.1136/bmjopen-2012-002542.CrossRefGoogle ScholarPubMed
Cuijpers, P., Sijbrandij, M., Koole, S.L., Andersson, G., Beekman, A.T., Reynolds, C.F. III.. The efficacy of psychotherapy and pharmacotherapy in treating depressive and anxiety disorders: a meta-analysis of direct comparisons. World Psychiatry 2013;12:137–148.CrossRefGoogle ScholarPubMed
Cuijpers, P., Turner, E.H., Koole, S.L., van Dijke, A., Smit, F.What is the threshold for a clinically relevant effect? The case of major depressive disorders. Depress Anx 2014;31:374–378.CrossRefGoogle ScholarPubMed
Cuijpers, P., van Straten, A., van Oppen, P., Andersson, G.Are psychological and pharmacological interventions equally effective in the treatment of adult depressive disorders? A meta-analysis of comparative studies. J Clin Psychiatry 2008;69:1675–1685.CrossRefGoogle Scholar
Cuijpers, P., van Straten, A., Warmerdam, L., Andersson, G.Psychological treatment of depression: a meta-analytic database of randomized studies. BMC Psychiatry 2008;8:36.CrossRefGoogle ScholarPubMed
David, D., Szentagotai, A., Lupu, V., Cosman, D.Rational emotive behavior therapy, cognitive therapy, and medication in the treatment of major depressive disorder: a randomized clinical trial, post-treatment outcomes, and 6-month follow-up. J Clin Psychol 2008;64:728–746.CrossRefGoogle Scholar
Dekker, J.J.M., Koelen, J.A., Van, H.L., Schoevers, R.A., Peen, J., Hendriksen, M., et al.Speed of action: the relative efficacy of short psychodynamic supportive psychotherapy and pharmacotherapy in the first 8 weeks of a treatment algorithm for depression. J Affective Disord 2008;109:183–188.CrossRefGoogle ScholarPubMed
Dunlop, B.W., Kelley, M.E., Mletzko, T.C., Velasquez, C.M., Craighead, W.E., Mayberg, H.S.Depression beliefs, treatment preference, and outcomes in a randomized trial for major depressive disorder. J Psychiatr Res 2012;46:375–381.CrossRefGoogle Scholar
Dunner, D.L., Schmaling, K.B., Hendrickson, H., Becker, J., Lehman, A., Bea, C.Cognitive therapy versus fluoxetine in the treatment of dysthymic disorder. Depress 1996;4:34–41.3.0.CO;2-F>CrossRefGoogle ScholarPubMed
Duval, S., Tweedie, R.Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000;56:455–463.CrossRefGoogle ScholarPubMed
Elkin, I., Shea, M.T., Watkins, J.T., Imber, S.D., Sotsky, S.M., Collins, J.F., et al.General effectiveness of treatments. Arch Gen Psychiatry 1989;46:971–982.CrossRefGoogle ScholarPubMed
Finkenzeller, W., Zobel, I., Rietz, S., Schramm, E., Berger, M.Interpersonal psychotherapy and pharmacotherapy for post-stroke depression. Feasibility and effectiveness. Nervenarzt 2009;80:805–812.CrossRefGoogle ScholarPubMed
Fisher, S., Greenberg, R.P.How sound is the double-blind design for evaluating psychotropic drugs?. J Nerv Ment Dis 1993;181:345–350.CrossRefGoogle ScholarPubMed
Fournier, J.C., DeRubeis, R.J., Hollon, S.D., Dimidjian, S., Amsterdam, J.D., Shelton, R.C., et al.Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA 2010;303:47–53.CrossRefGoogle ScholarPubMed
Frank, E., Cassano, G.B., Rucci, P., Thompson, W.K., Kraemer, H.C., Fagiolini, A., et al.Predictors and moderators of time to remission of major depression with interpersonal psychotherapy and SSRI pharmacotherapy. Psychol Med 2011;41:151–162.CrossRefGoogle ScholarPubMed
Hedges, L.V., Olkin, I.Statistical methods for meta-analysis. San Diego, CA: Academic Press; 1985.Google Scholar
Hegerl, U., Allgaier, A.K., Henkel, V., Mergl, R.Can effects of antidepressants in patients with mild depression be considered as clinically significant?. J Affect Disord 2012;138:183–191.CrossRefGoogle ScholarPubMed
Hegerl, U., Hautzinger, M., Mergl, R., Kohnen, R., Schütze, M., Scheunemann, W., et al.Effects of pharmacotherapy and psychotherapy in depressed primary-care patients: a randomized, controlled trial including a patients? Choice arm. Int J Neuropsychopharmacol 2010;13:31–44.CrossRefGoogle ScholarPubMed
Hegerl, U., Mergl, R.The clinical significance of antidepressant treatment effects cannot be derived from placebo-verum response differences. J Psychopharmacol 2010;24:445–448.CrossRefGoogle ScholarPubMed
Higgins, J.P.T., Green, S.Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. 2011. http://www.cochrane-handbook.org.Google Scholar
Higgins, J.P., Thompson, S.G., Deeks, J.J., Altman, D.G.Measuring inconsistency in meta-analyses. BMJ 2003;327:557–560.CrossRefGoogle ScholarPubMed
Hollon, S.D., DeRubeis, R.J., Evans, M.D., Wiemer, M.J., Garvey, M.J., Grove, W.M., et al.Cognitive therapy and pharmacotherapy for depression: singly and in combination. Arch Gen Psychiatry 1992;49:774–781.CrossRefGoogle ScholarPubMed
Ioannidis, J.P.A., Patsopoulos, N.A., Evangelou, E.Uncertainty in heterogeneity estimates in meta-analyses. BMJ 2007;335:914–916.CrossRefGoogle ScholarPubMed
Jarrett, R.B., Schaffer, M., McIntire, D., Witt-Browder, A., Kraft, D., Risser, R.C.Treatment of atypical depression with cognitive therapy or phenelzine: a double-blind, placebo-controlled trial. Arch Gen Psychiatry 1999;56:431–437.CrossRefGoogle ScholarPubMed
Keller, M.B., McCullough, J.P., Klein, D.N., Arnow, B., Dunner, D.L., Gelenberg, A.J., et al.A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med 2000;342:1462–1470.CrossRefGoogle ScholarPubMed
Kirsch, I.Benefits of antidepressants over placebo limited except in very severe depression. Evid Based Ment Health 2010;13:49.CrossRefGoogle ScholarPubMed
Kraemer, H.C., Kupfer, D.J.Size of treatment effects and their importance to clinical research and practice. Biol Psychiatry 2006;59:990–996.CrossRefGoogle ScholarPubMed
Laupacis, A., Sackett, D.L., Roberts, R.S.An assessment of clinically useful measures of the consequences of treatment. New Engl J Med 1988;318:1728–1733.CrossRefGoogle ScholarPubMed
Lesperance, F., Frasure-Smith, N., Koszycki, D., Lalibert, M.A., van Zyl, L.T., Baker, B., et al.Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian cardiac randomized evaluation of antidepressant and psychotherapy efficacy (CREATE) trial. JAMA 2007;297:367–379.CrossRefGoogle ScholarPubMed
Liberati, A., Altman, D.G., Tetzlaff, J., Mulrow, C., Gøtzsche, P.C., et al.The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 2009;6(7):e1000100. http://dx.doi.org/10.1371/journal.pmed.1000100.CrossRefGoogle ScholarPubMed
Markowitz, J.C., Kocsis, J.H., Bleiberg, K.L., Christos, P.J., Sacks, M.A comparative trial of psychotherapy and pharmacotherapy for “pure” dysthymic patients. J Affect Dis 2005;89:167–175.CrossRefGoogle ScholarPubMed
Marshall, M.B., Zuroff, D.C., McBride, C., Bagby, R.M.Self-criticism predicts differential response to treatment for major depression. J Clin Psychol 2008;64:231–244.CrossRefGoogle ScholarPubMed
Martin, S.D., Martin, E., Rai, S.S., Richardson, M.A., Royall, R.Brain blood flow changes in depressed patients treated with interpersonal psychotherapy or venlafaxine hydrochloride: preliminary findings. Arch Gen Psychiatry 2001;58:641–648.CrossRefGoogle ScholarPubMed
McBride, C., Segal, Z., Kennedy, S., Gemar, M.Changes in autobiographical memory specificity following cognitive behavior therapy and pharmacotherapy for major depression. Psychopathol 2007;40:147–152.CrossRefGoogle ScholarPubMed
McHugh, R.K., Whitton, S.W., Peckham, A.D., Welge, J.A., Otto, M.W.Patient preference for psychological vs pharmacological treatment of psychiatric disorders: a meta-analytic review. J Clin Psychiatry 2013;74:595–602.CrossRefGoogle ScholarPubMed
McKnight, D.L., Nelson-Gray, R.O., Barnhill, J.Dexamethasone suppression test and response to cognitive therapy and antidepressant medication. Behav Ther 1992;23:99–111.CrossRefGoogle Scholar
Mohr, D.C., Boudewyn, A.C., Goodkin, D.E., Bostrom, A., Epstein, L.Comparative outcomes for individual cognitive-behavior therapy, supportive-expressive group psychotherapy, and sertraline for the treatment of depression in multiple sclerosis. J Consult Clin Psychol 2001;69:942–949.CrossRefGoogle ScholarPubMed
Mohr, D.C., Ho, J., Hart, S.L., Baron, K.G., Berendsen, M., Beckner, V., et al.Control condition design and implementation features in controlled trials: a meta-analysis of trials evaluating psychotherapy for depression. Transl Behav Med 2014. [epub ahead of print]CrossRefGoogle ScholarPubMed
Mohr, D.C., Spring, B., Freedland, K.E., Beckner, V., Arean, P., Hollon, S.D., et al.The selection and design of control conditions for randomized controlled trials of psychological interventions. Psychother Psychosom 2009;78:275–284.CrossRefGoogle ScholarPubMed
Moncrieff, J., Wessely, S., Hardy, R.Active placebos versus antidepressants for depression. Cochrane Database Syst Rev 2004;1:CD003012.Google Scholar
Moradveisi, L., Huibers, M.J.H., Renner, F., Arasteh, M., Arntz, A.Behavioural activation v. antidepressant medication for treating depression in Iran: randomised trial. Br J Psychiatry 2013;202:204–211.CrossRefGoogle ScholarPubMed
Murphy, G.E., Simons, A.D., Wetzel, R.D., Lustman, P.J.Cognitive therapy and pharmacotherapy. Singly and together in the treatment of depression. Arch Gen Psychiatry 1984;41:33–41.CrossRefGoogle ScholarPubMed
Mynors-Wallis, L.M., Gath, D.H., Day, A., Baker, F.Randomised controlled trial of problem solving treatment, antidepressant medication, and combined treatment for major depression in primary care. BMJ 2000;320:26–30.CrossRefGoogle ScholarPubMed
Mynors-Wallis, L.M., Gath, D.H., Lloyd-Thomas, A.R., Tomlinson, D.Randomised controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care. BMJ 1995;310:441–445.CrossRefGoogle ScholarPubMed
Nutt, D.J., Sharpe, M.Uncritical positive regard? Issues in the efficacy and safety of psychotherapy. J Psychopharmacology 2008;22:3–6.CrossRefGoogle ScholarPubMed
Orsini, N., Higgins, J., Bottai, M., Buchan, I.Heterogi: Stata module to quantify heterogeneity in a meta-analysis. 2005 [accessed 27 February 2013] http://EconPapers.repec.org/RePEc:boc:bocode:s449201.Google Scholar
Ravindran, A.V., Anisman, H., Merali, Z., Charbonneau, Y., Telner, J., Bialik, R.J., et al.Treatment of primary dysthymia with group cognitive therapy and pharmacotherapy: clinical symptoms and functional impairments. Am J Psychiatry 1999;156:1608–1617.CrossRefGoogle ScholarPubMed
Reynolds, C.F., Miller, M.D., Pasternak, R.E., Frank, E., Perel, J.M., Cornes, C., et al.Treatment of bereavement-related major depressive episodes in later life: a controlled study of acute and continuation treatment with nortriptyline and interpersonal psychotherapy. Am J Psychiatry 1999;156:202–208.Google ScholarPubMed
Rush, A.J., Beck, A.T., Hollon, S.D., et al.Comparative efficacy of cognitive therapy and pharmacotherapy in the treatment of depressed outpatients. Cogn Ther Res 1977;1:17–37.CrossRefGoogle Scholar
Rutherford, B.R., Roose, S.P.A model of placebo response in antidepressant clinical trials. Am J Psychiatry 2013;170:723–733.CrossRefGoogle Scholar
Salminen, J.K., Karlsson, H., Hietala, J., Kajander, J., Aalto, S., Markkula, J., et al.Short-term psychodynamic psychotherapy and fluoxetine in major depressive disorder: a randomized comparative study. Psychother Psychosom 2008;77:351–357.CrossRefGoogle ScholarPubMed
Shamsaei, F., Rahimi, A., Zarabian, M.K., Sedehi, M.Efficacy of pharmacotherapy and cognitive therapy, alone and in combination in major depressive disorder. Hong Kong J Psychiatry 2008;18:76–80.Google Scholar
Sharp, D.J., Chew-Graham, C., Tylee, A., Lewis, G., Howard, L., Anderson, I., et al.A pragmatic randomised controlled trial to compare antidepressants with a community-based psychosocial intervention for the treatment of women with postnatal depression: the RESPOND trial. Health Technol Assess 2010;14:43.CrossRefGoogle ScholarPubMed
Sinyor, M., Levitt, A.J., Cheung, A.H., Schaffer, A., Kiss, A., Dowlati, Y., et al.Does inclusion of a placebo arm influence response to active antidepressant treatment in randomized controlled trials? Results from pooled and meta-analyses. J Clin Psychiatry 2010;71:270–279.CrossRefGoogle ScholarPubMed
Sneed, J.R., Rutherford, B.R., Rindskopf, D., Lane, D.T., Sackeim, H.A., Roose, S.P.Design makes a difference: a meta-analysis of antidepressant response rates in placebo-controlled versus comparator trials in late-life depression. Am J Geriat Psychiatry 2008;16:65–73.CrossRefGoogle ScholarPubMed
Thompson, L.W., Coon, D.W., Gallagher-Thompson, D., Sommer, B.R., Koin, D.Comparison of desipramine and cognitive/behavioral therapy in the treatment of elderly outpatients with mild-to-moderate depression. Am J Geriatr Psychiatry 2001;9:225–240.CrossRefGoogle ScholarPubMed
Williams, J.W., Barrett, J., Oxman, T., Frank, E., Katon, W., Sullivan, M., et al.Treatment of dysthymia and minor depression in primary care: a randomized controlled trial in older adults. JAMA 2000;284:1519–1526.CrossRefGoogle ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.