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Efficacy of Pharmacotherapy and Psychotherapy for Adult Psychiatric Disorders A Systematic Overview of Meta-analyses

Maximilian Huhn, MD1; Magdolna Tardy, MSc1; Loukia Maria Spineli, MSc3; Werner Kissling, MD1; Hans Förstl, MD1; Gabriele Pitschel-Walz, PhD1; Claudia Leucht, MD1,2; Myrto Samara, MD1; Markus Dold, MD1; John M. Davis, MD4; Stefan Leucht, MD1,2,5
[+] Author Affiliations
1Department of Psychiatry and Psychotherapy, Technische Universität München, München, Germany
2Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, England
3Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, University Campus, Ioannina, Greece
4Psychiatric Institute, University of Illinois at Chicago
5Institute of Psychiatry, King’s College London, London, England
JAMA Psychiatry. 2014;71(6):706-715. doi:10.1001/jamapsychiatry.2014.112.
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Importance  There is debate about the effectiveness of psychiatric treatments and whether pharmacotherapy or psychotherapy should be primarily used.

Objectives  To perform a systematic overview on the efficacy of pharmacotherapies and psychotherapies for major psychiatric disorders and to compare the quality of pharmacotherapy and psychotherapy trials.

Evidence Review  We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Library (April 2012, with no time or language limit) for systematic reviews on pharmacotherapy or psychotherapy vs placebo, pharmacotherapy vs psychotherapy, and their combination vs either modality alone. Two reviewers independently selected the meta-analyses and extracted efficacy effect sizes. We assessed the quality of the individual trials included in the pharmacotherapy and psychotherapy meta-analyses with the Cochrane risk of bias tool.

Findings  The search yielded 45 233 results. We included 61 meta-analyses on 21 psychiatric disorders, which contained 852 individual trials and 137 126 participants. The mean effect size of the meta-analyses was medium (mean, 0.50; 95% CI, 0.41-0.59). Effect sizes of psychotherapies vs placebo tended to be higher than those of medication, but direct comparisons, albeit usually based on few trials, did not reveal consistent differences. Individual pharmacotherapy trials were more likely to have large sample sizes, blinding, control groups, and intention-to-treat analyses. In contrast, psychotherapy trials had lower dropout rates and provided follow-up data. In psychotherapy studies, wait-list designs showed larger effects than did comparisons with placebo.

Conclusions and Relevance  Many pharmacotherapies and psychotherapies are effective, but there is a lot of room for improvement. Because of the multiple differences in the methods used in pharmacotherapy and psychotherapy trials, indirect comparisons of their effect sizes compared with placebo or no treatment are problematic. Well-designed direct comparisons, which are scarce, need public funding. Because patients often benefit from both forms of therapy, research should also focus on how both modalities can be best combined to maximize synergy rather than debate the use of one treatment over the other.

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Figure 1.
Comparison of Effect Sizes in Meta-analyses of Acute and Maintenance Treatment in Pharmacotherapy and Psychotherapy

For all disorders, we present the standardized mean difference (SMD) of pharmacotherapy (orange) and psychotherapy (blue) in acute (squares) and maintenance (circles) treatment vs placebo. We always chose the efficacy outcome with the most participants as reported in the Supplement (eTable 5). If there was more than 1 treatment for 1 disorder (eg, dementia [acetylcholinesterase inhibitors and memantine], bipolar depression [antidepressants, antipsychotics, and mood stabilizers], or opiate addiction [buprenorphine and methadone]), we presented their mean effect size. Italicized SMDs were estimated from odds ratios. ADHD indicates attention-deficit/hyperactivity disorder; DBT, dialective-behavioral therapy; GAD, generalized anxiety disorder; MDD, major depressive disorder; NI, not indicated; OCD, obsessive-compulsive disorder; PT, psychotherapy; and PTSD, posttraumatic stress disorder.aWe included only studies examining MDD.bMixed depressive disorder was available.cOnly 1 study was available.

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Figure 2.
Comparison of Effect Sizes in Meta-analyses of Direct Comparisons of Pharmacotherapy and Psychotherapy

The outcome in all studies was reduction of overall symptoms except for relapse prevention in depression. Italicized standardized mean differences (SMDs) were estimated from odds ratios. NI indicates not indicated.aDrug vs psychodynamic psychotherapy.

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Figure 3.
Comparison of Effect Sizes in Meta-analyses of Alone vs Combined Pharmacotherapy or Psychotherapy

The outcome in all studies was reduction of overall symptoms. Italicized standardized mean differences (SMDs) were estimated from odds ratios. CBT indicates cognitive-behavioral therapy; PDT, psychodynamic therapy.aFor panic disorder, the effect size is the mean of 2 meta-analyses.72,75

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Figure 4.
Methodologic Characteristics of Individual Studies in Psychotherapy and Pharmacotherapy Meta-analyses on Acute Treatment According to the Cochrane Risk of Bias Tool

Percentage of individual studies within the meta-analyses with appropriate components of design. The randomization and allocation methods were not described in 60% and 87% of psychotherapy trials and 86% and 94% of pharmacotherapy trials, respectively; therefore, they were coded as unclear, which was grouped with studies that were not randomized. Contemporaneous controls included patients receiving placebo, treatment as usual, or ineffective therapy in contrast to wait list or no treatment. Statistical significance was examined with χ2 tests for all parameters except overall dropout rates, which were compared with the Mann-Whitney test.aP = .08.bP = .36.cP < .001.

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Placebo effect a factor in results of pharmacotherapy v. psychotherapy trial?
Posted on May 3, 2014
Dr. Eugene J. Koprowski
King's College, Institute of Psychiatry, University of London
Conflict of Interest: None Declared

I'm curious to know why the placebo effect was not really considered important by the researchers in this systematic overview, particularly when it comes to the effectiveness of pharmacotherapies? The placebo effect is an important element in the healing process, especially for psychiatric disorders. One may even consider there to be a \"transference\" of sorts with healing power attributed to certain pharmacotherapies by certain patients. Freud and Jung did not prescribe anti-depressants or anxiolytics in their day, and yet they helped many patients, though they did use other modalities in addition to talk therapy (e.g. hydrotherapy). This study of the placebo effect of brand name anti-depressants and anxiolytics is something that should be investigated now and would be helpful to clinicians, who could combine the power of suggestion with the placebo effect in daily medication management situations.


McQueen, D., Cohen, S., St John-Smith, P., & Rampes, H. (2013). Rethinking placebo in psychiatry: the range of placebo effects. Advances in psychiatric treatment, 19(3), 162-170.

Moerman, D. E. (2013). Against the “placebo effect”: A personal point of view. Complementary therapies in medicine, 21(2), 125-130.

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