Skip to main content

Comparison of psychotherapies for adult depression to pill placebo control groups: a meta-analysis

  • P. Cuijpers (a1) (a2), E. H. Turner (a3) (a4), D. C. Mohr (a5), S. G. Hofmann (a6), G. Andersson (a7) (a8), M. Berking (a9) and J. Coyne (a10)...

The effects of antidepressants for treating depressive disorders have been overestimated because of selective publication of positive trials. Reanalyses that include unpublished trials have yielded reduced effect sizes. This in turn has led to claims that antidepressants have clinically insignificant advantages over placebo and that psychotherapy is therefore a better alternative. To test this, we conducted a meta-analysis of studies comparing psychotherapy with pill placebo.


Ten 10 studies comparing psychotherapies with pill placebo were identified. In total, 1240 patients were included in these studies. For each study, Hedges’ g was calculated. Characteristics of the studies were extracted for subgroup and meta-regression analyses.


The effect of psychotherapy compared to pill placebo at post-test was g = 0.25 [95% confidence interval (CI) 0.14–0.36, I 2 = 0%, 95% CI 0–58]. This effect size corresponds to a number needed to treat (NNT) of 7.14 (95% CI 5.00–12.82). The psychotherapy conditions scored 2.66 points lower on the Hamilton Depression Rating Scale (HAMD) than the placebo conditions, and 3.20 points lower on the Beck Depression Inventory (BDI). Some indications for publication bias were found (two missing studies). We found no significant differences between subgroups of the studies and in meta-regression analyses we found no significant association between baseline severity and effect size.


Although there are differences between the role of placebo in psychotherapy and pharmacotherapy research, psychotherapy has an effect size that is comparable to that of antidepressant medications. Whether these effects should be deemed clinically relevant remains open to debate.

Corresponding author
* Address for correspondence: P. Cuijpers, Ph.D., Professor of Clinical Psychology, Department of Clinical Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands. (Email:
Hide All
Barber J, Barrett MS, Gallop R, Rynn MA, Rickels K (2012). Short-term dynamic psychotherapy versus pharmacotherapy for major depressive disorder: a randomized, placebo-controlled trial. Journal of Clinical Psychiatry 73, 6673.
Barrett JE, Williams JW, Oxman TE, Frank E, Katon W, Sullivan M, Hegel MT, Cornell JE, Sengupta AS (2001). Treatment of dysthymia and minor depression in primary care: a randomized trial in patients aged 18 to 59. Journal of Family Practice 50, 405412.
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961). An inventory for measuring depression. Archives of General Psychiatry 4, 561571.
Borenstein M, Hedges LV, Higgins JPT, Rothstein HR (2009). Introduction to Meta-Analysis. Wiley: Chichester, UK.
Cuijpers P, Smit F, Bohlmeijer ET, Hollon SD, Andersson G (2010 a). Is the efficacy of cognitive behaviour therapy and other psychological treatments for adult depression overestimated? A meta-analytic study of publication bias. British Journal of Psychiatry 196, 173178.
Cuijpers P, van Straten A, Andersson G, van Oppen P (2008 a). Psychotherapy for depression in adults: a meta-analysis of comparative outcome studies. Journal of Consulting and Clinical Psychology 76, 909922.
Cuijpers P, van Straten A, Bohlmeijer E, Hollon SD, Andersson G (2010 b). The effects of psychotherapy for adult depression are overestimated: a meta-analysis of study quality and effect size. Psychological Medicine 40, 211223.
Cuijpers P, van Straten A, van Oppen P, Andersson G (2008 b). Are psychological and pharmacological interventions equally effective in the treatment of adult depressive disorders? A meta-analysis of comparative studies. Journal of Clinical Psychiatry 69, 16751685.
Cuijpers P, van Straten A, Warmerdam L, Andersson G (2008 c). Psychological treatment of depression: a meta-analytic database of randomized studies. BMC Psychiatry 8, 36.
Cuijpers P, van Straten A, Warmerdam L, Smits N (2008 d). Characteristics of effective psychological treatments of depression: a meta-regression analysis. Psychotherapy Research 18, 225236.
David D, Szentagotai A, Lupu V, Cosman D (2008). Rational emotive behavior therapy, cognitive therapy, and medication in the treatment of major depressive disorder: a randomized clinical trial, posttreatment outcomes, and six month follow-up. Journal of Clinical Psychology 64, 728746.
DeRubeis RJ, Hollon SD, Amsterdam JD, Shelton RC, Young PR, Salomon RM (2005). Cognitive therapy vs medications in the treatment of moderate to severe depression. Archives of General Psychiatry 62, 409416.
Dimidjian S, Hollon SD, Dobson KS, Schmaling KB, Kohlenberg RJ, Addis ME (2006). Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of adults with major depression. Journal of Consulting and Clinical Psychology 74, 658670.
Dobson KS, Hollon SD, Dimidjian S, Schmaling KB, Kohlenberg RJ, Gallop RJ, Rizvi SL, Gollan JK (2008). Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the prevention of relapse and recurrence in major depression. Journal of Consulting and Clinical Psychology 76, 468477.
Duval S, Tweedie R (2000). Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56, 455463.
Dwight-Johnson M, Sherbourne CD, Liao D, Wells KB (2000). Treatment preferences among depressed primary care patients. Journal of General Internal Medicine 15, 527534.
Elkin I, Shea MT, Watkins JT, Imber SD, Sotsky SM, Collins JF (1989). National Institute of Mental Health Treatment of Depression Collaborative Research Program: general effectiveness of treatments. Archives of General Psychiatry 46, 971982.
Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC (2010). Antidepressant drug effects and depression severity: a patient-level meta-analysis. Journal of the American Medical Association 303, 4753.
Hamilton M (1960). A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 23, 5662.
Hedges LV, Olkin I (1985). Statistical Methods for Meta-Analysis. Academic Press: San Diego, CA.
Hegerl U, Hautzinger M, Mergl R, Kohnen R, Schütze M, Scheunemann W, Allgaier AK, Coyne J, Henkel V (2010). Effects of pharmacotherapy and psychotherapy in depressed primary-care patients: a randomized, controlled trial including a patients’ choice arm. International Journal of Neuropsychopharmacology 13, 3144.
Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003). Measuring inconsistency in meta-analyses. British Medical Journal 327, 557560.
Higgins JPT, Green S (eds) (2008). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.0.1 [updated September 2008]. Wiley: Chichester, UK.
Hollon SD, DeRubeis RJ, Shelton RC, Amsterdam JD, Salomon RM, O'Reardon JP, Lovett ML, Young PR, Haman KL, Freeman BB, Gallop R (2005). Prevention of relapse following cognitive therapy versus medication in moderate to severe depression. Archives of General Psychiatry 62, 417422.
Hypericum Depression Trial Study Group (2002). Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. Journal of the American Medical Association 287, 18071814.
Imel ZE, Malterer MB, McKay KM, Wampold BE (2008). A meta-analysis of psychotherapy and medication in unipolar depression and dysthymia. Journal of Affective Disorders 110, 197206.
Ioannidis JPA, Patsopoulos NA, Evangelou E (2007). Uncertainty in heterogeneity estimates in meta-analyses. British Medical Journal 335, 914916.
Jarrett RB, Schaffer M, McIntire D, Witt-Browder A, Kraft D, Risser RC (1999). Treatment of atypical depression with cognitive therapy or phenelzine: a double-blind, placebo-controlled trial. Archives of General Psychiatry 56, 431437.
Katz R, Shaw BF, Vallis TM, Kaiser AS (1995). The assessment of severity and symptom patterns in depression. In Handbook of Depression (ed. Beckham E. E. and Leber W. R.), 2nd edn, pp. 6185. Guilford Press: New York.
Kirsch I (2009). The Emperor's New Drugs: Exploding the Antidepressant Myth. The Bodley Head: London.
Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT (2008). Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Medicine 5, 250268.
Kraemer HC, Kupfer DJ (2006). Size of treatment effects and their importance to clinical research and practice. Biological Psychiatry 59, 990996.
Laupacis A, Sackett DL, Roberts RS (1988). An assessment of clinically useful measures of the consequences of treatment. New England Journal of Medicine 318, 17281733.
Luborsky L, Diguer L, Seligman DA, Rosenthal R, Krause ED, Johnson S, Halperin G, Bishop M, Berman JS, Schweizer E (1999). The researcher's own therapy allegiances: a ‘wild card’ in comparisons of treatment efficacy. Clinical Psychology: Science and Practice 6, 95106.
Melander H, Ahlqvist-Rastad J, Meijer G, Beermann B (2003). Evidence b(i)ased medicine selective reporting from studies sponsored by pharmaceutical industry: review of studies in new drug applications. British Medical Journal 326, 11711173.
Mohr DC, Spring B, Freedland KE, Beckner V, Arean P, Hollon SD, Ockene J, Kaplan R (2009). The selection and design of control conditions for randomized controlled trials of psychological interventions. Psychotherapy and Psychosomatics 78, 275284.
Mynors-Wallis LM, Gath DH, Lloyd-Thomas AR, Tomlinson D (1995). Randomised controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care. British Medical Journal 310, 441–335.
NICE (2004). Depression: management of depression in primary and secondary care. Clinical Practice Guideline CG23. National Institute for Clinical Excellence: London.
Orsini N, Higgins J, Bottai M, Buchan I (2005). Heterogi: Stata module to quantify heterogeneity in a meta-analysis ( Accessed 27 February 2013.
Posternak MA, Zimmerman M (2007). Therapeutic effect of follow-up assessments on antidepressant and placebo response rates in antidepressant efficacy trials: meta-analysis. British Journal of Psychiatry 190, 287292.
Rief W, Nestoriuc Y, Weiss S, Welzel E, Barsky AJ, Hofmann SG (2009). Meta-analysis of the placebo response in antidepressant trials. Journal of Affective Disorders 118, 19.
Sloane RB, Staples FR, Schneider LS (1985). Interpersonal therapy versus nortriptyline for depression in the elderly. In Clinical and Pharmacological Studies in Psychiatric Disorders (ed. Burrows G., Norman T. R. and Dermerstein L.), pp. 344346. John Libbey: London.
Temple R, Ellenberg SS (2000). Placebo-controlled trials and active-control trials in the evaluation of new treatments. Part 1: Ethical and scientific issues. Annals of Internal Medicine 133, 455463.
Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R (2008). Selective publication of antidepressant trials and its influence on apparent efficacy. New England Journal of Medicine 358, 252260.
van Schaik DJF, Klijn AFJ, van Hout HPJ, van Marwijk HWJ, Beekman ATF, de Haan M, van Dyck R (2004). Patients’ preferences in the treatment of depressive disorder in primary care. General Hospital Psychiatry 26, 184189.
Williams JW Jr., Barrett J, Oxman T, Frank E, Katon W, Sullivan M, Cornell J, Sengupta A (2000). Treatment of dysthymia and minor depression in primary care: a randomized controlled trial in older adults. Journal of the American Medical Association 284, 15191526.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Type Description Title
Supplementary Materials

Cuijpers supplementary material
Cuijpers supplementary material

 Word (183 KB)
183 KB


Altmetric attention score

Full text views

Total number of HTML views: 14
Total number of PDF views: 148 *
Loading metrics...

Abstract views

Total abstract views: 1016 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 19th November 2017. This data will be updated every 24 hours.