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Cited by 540Treatment of Major DepressionPsychotherapy Techniques and ApplicationsAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

A network meta‐analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression

Open access
Cuijpers, Pim, Noma, Hisashi, Karyotaki, Eirini, Vinkers, Christiaan H., Cipriani, Andrea, Furukawa, Toshi A.·2020·World Psychiatry
DOI 10.1002/wps.20701PMC PMC6953550
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Abstract

No network meta‐analysis has examined the relative effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression, while this is a very important clinical issue. We conducted systematic searches in bibliographical databases to identify randomized trials in which a psychotherapy and a pharmacotherapy for the acute or long‐term treatment of depression were compared with each other, or in which the combination of a psychotherapy and a pharmacotherapy was compared with either one alone. The main outcome was treatment response (50% improvement between baseline and endpoint). Remission and acceptability (defined as study drop‐out for any reason) were also examined. Possible moderators that were assessed included chronic and treatment‐resistant depression and baseline severity of depression. Data were pooled as relative risk (RR) using a random‐effects model. A total of 101 studies with 11,910 patients were included. Depression in most studies was moderate to severe. In the network meta‐analysis, combined treatment was more effective than psychotherapy alone (RR=1.27; 95% CI: 1.14‐1.39) and pharmacotherapy alone (RR=1.25; 95% CI: 1.14‐1.37) in achieving response at the end of treatment. No significant difference was found between psychotherapy alone and pharmacotherapy alone (RR=0.99; 95% CI: 0.92‐1.08). Similar results were found for remission. Combined treatment (RR=1.23; 95% CI: 1.05‐1.45) and psychotherapy alone (RR=1.17; 95% CI: 1.02‐1.32) were more acceptable than pharmacotherapy. Results were similar for chronic and treatment‐resistant depression. The combination of psychotherapy and pharmacotherapy seems to be the best choice for patients with moderate depression. More research is needed on long‐term effects of treatments (including cost‐effectiveness), on the impact of specific pharmacological and non‐pharmacological approaches, and on the effects in specific populations of patients.

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Crossref · 10.1002/wps.20701

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 22 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Network meta-analysis showed that combined treatment produced higher response rates than pharmacotherapy alone (RR=1.25, 95% CI 1.14-1.37).

    “combined treatment was more effective than psychotherapy alone (RR=1.27;95% CI: 1.14-1.39)and pharmacotherapy alone (RR=1.25;95% CI: 1.14-1.37) in achieving response at the end of treatment”
    Quote in the paperSubstantial claim
  • Findingown data

    Combined treatment was superior to pill placebo for response (RR=1.47, 95% CI 1.20-1.75).

    “and for combined treatment com pared to pill placebo (RR=1.47,95% CI: 1.201.75).”
    Quote in the paperSubstantial claim
  • Findingown data

    Network meta-analysis showed that combined treatment produced higher response rates than psychotherapy alone (RR=1.27, 95% CI 1.14-1.39).

    “In the network meta-analysis, combined treatment was more effective than psychotherapy alone (RR=1.27;95% CI: 1.14-1.39)”
    Quote in the paperSubstantial claim
  • Findingown data

    In chronic or treatment-resistant depression, combined treatment was more effective than psychotherapy alone (RR=1.59, 95% CI 1.23-2.04).

    “superior effects for combined treatment versus psychotherapy or pharmacotherapy alone (RR=1.59,95% CI: 1.232.04 and RR=1.39,95% CI: 1.15 1.67)”
    Quote in the paperSubstantial claim
  • Findingown data

    In chronic or treatment-resistant depression, there was no significant difference between psychotherapy and pharmacotherapy (RR=0.87, 95% CI 0.68-1.10).

    “comparable effects for psychotherapy and pharmaco therapy (RR=0.87,95% CI: 0.681.10).”
    Quote in the paperSubstantial claim
  • May combine two claims. 14
  • Classified as probably not a substantial claim. 20

  • May combine two claims.

    Findingown data

    SUCRA ranked combined treatment best for response (99.9), remission (93.0), standardized mean difference (95.6), and acceptability (78.7).

    “In the SUCRA analyses, combined treatment ranked clearly best for response (99.9), remission (93.0) and SMD (95.6), as well as for acceptability (78.7).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    An individual format was used in 81 psychotherapy studies.

    “an individual format was used in 81 psychotherapy studies”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    CBT was the most commonly used psychotherapy (48 trials).

    “CBT was the most commonly used psychotherapy (48 trials)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    A total of 101 studies with 11,910 patients were included.

    “A total of 101 studies met inclusion criteria (11,910 participants overall: 2,587 randomized to combined treatment, 3,625 to psychotherapy, 4,769 to pharmacotherapy, 632 to placebo and 297 to psychotherapy plus placebo)”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    47 trials recruited patients exclusively from clinical samples, and 75 were aimed at unselected adults.

    “In brief, 47 trials recruited patients exclu sively from clinical samples, and 75 were aimed at unselected adults.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The time from pre to posttest ranged from 4 to 36 weeks, with the majority of comparisons (78%) ranging from 8 to 16 weeks.

    “The time from pre to posttest ranged from 4 to 36 weeks, with the majority of comparisons (78%) ranging from 8 to 16 weeks.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    SSRIs were the most frequently used medications.

    “SSRIs were the most frequently used medications”
    Quote in the paperNot a substantial claim

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    Findingown data

    In 36 of 51 trials reporting the mean baseline HAMD score, the severity of depression was moderate.

    “In 36 of 51 trials reporting the mean baseline HAMD score, the severity of depression was moderate.”
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    Findingown data

    In total, 115 comparisons were available in the included studies.

    “In total, 115 comparisons were available in the studies.”
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    Findingown data

    Thirteen studies were aimed at patients with chronic or treatment-resistant depression.

    “Thirteen studies were aimed at patients with chronic or treatmentresistant depression.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Egger's test was significant for combined treatment versus pharmacotherapy (p=0.02) and for combined treatment versus psychotherapy plus placebo (p=0.02).

    “Egger's test was only significant for combined treatment versus pharmaco therapy (p=0.02) and for combined treatment versus psycho therapy plus placebo (p=0.02).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Pharmacotherapy was judged adequate in 67 trials.

    “phar macotherapy was judged adequate in 67 trials.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Risk-of-bias components: 48 studies reported adequate sequence generation, 40 reported allocation by an independent party, 81 reported blinding of outcome assessors or used only self-report outcomes, and 58 conducted intention-to-treat analyses.

    “A total of 48 studies reported an adequate sequence generation; 40 re ported allocation to conditions by an independent (third) party; and 81 reported blinding of outcome assessors or used only self report outcomes.Intentiontotreat analyses were conducted in 58 studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Sensitivity analyses showed that main outcomes were comparable across all analyses, with combined treatment superior and no significant difference between psychotherapy and pharmacotherapy.

    “The main outcomes were comparable across all analyses, with combined treatment being superior to psychotherapy or phar macotherapy alone, and no significant difference between psy chotherapy and pharmacotherapy.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    45 trials met all three psychotherapy quality criteria.

    “45 trials met all three quality cri teria.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Quality criteria distribution: 23 studies met all four criteria (28 when self-report was rated as low risk of bias), 19 met three, 19 met two, and 40 met one or none.

    “Twentythree studies met all four quality criteria (28 when selfreport was rated as low risk of bias), 19 met three cri teria, another 19 met two criteria, and the remaining 40 studies met one or none of the criteria.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    When response rate was not reported, it was imputed using a validated method.

    “When not reported, we imput ed response rate using a validated method 23 .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Conventional meta-analyses of direct comparisons suggest that psychotherapies and pharmacotherapies have comparable effects, with no or only minor differences.

    “Conventional metaanalyses of trials directly comparing psychotherapies and pharmacotherapies have suggested that, as classes of treatments, they have comparable effects, with no or only minor differenc es 7,8”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [7] source

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    Study design and conductnone given

    The protocol for this network meta-analysis was registered at PROSPERO (CRD42018114961).

    “The protocol for this network metaanalysis was registered at PROSPERO (CRD42018114961).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Two independent researchers screened all records and full texts, and disagreements were resolved through discussion.

    “All records and full texts were screened by two independent re searchers.Any disagreement was solved through discussion.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The combination of psychotherapy and pharmacotherapy may be more effective than either alone, but the evidence is not conclusive.

    “Other pairwise metaanalyses have found that the combination of psychotherapy and pharmacotherapy may be more effective than either of these alone 11,12 , although the evi dence is not conclusive 13,14 .”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [11] source

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  • Classified as probably not a substantial claim.

    Study design and conductcitation

    The consistency of the network was checked using tests of local and global inconsistency.

    “We checked the consistency of the network using tests of local and global inconsistency 29,30 .”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [29] source

      Not checked in the free run.

    • cites [30] source

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  • May combine two claims.

    Premisecitation

    Psychotherapies and pharmacotherapies are effective in treating adult depression.

    “It is wellestablished that psychotherapies and pharmaco logical therapies are effective in the treatment of adult depres sion.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [5] source

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    • cites [6] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Two independent researchers assessed risk of bias using four Cochrane criteria, and disagreements were resolved through discussion.

    “Two independent researchers assessed the risk of bias of in cluded studies using four criteria of the Cochrane tool 20 .Disa greements were solved through discussion.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] source

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  • May combine two claims.

    Premisecitation

    Network meta-analyses can combine multiple comparisons, use direct and indirect evidence, make better estimates, have more statistical power, and present consolidated comparisons.

    “Network metaanalyses can combine multiple comparisons in one analysis, are able to use direct and indirect evidence, and thus make optimal use of all available evidence.These analyses consequently make better estimates of the differences between treatments, have more statistical power to examine moderators of outcome, and can present consolidated comparisons among alternative treatments 16 .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Earlier research has suggested possible differences in efficacy and acceptability among specific medication types.

    “Finally, previ ous research has indicated that there may be some differences in efficacy and acceptability among specific types of medications 6 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Premisecitation

    A prior pairwise meta-analysis found that medication added a small effect to combined treatment.

    “A previous pairwise metaanalysis suggested that the medication contributed to the effects of com bined treatment with a small effect size 144 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [144] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Earlier meta-analytic work indicated that in depression and anxiety, combining psychotherapy and pharmacotherapy yields an effect equal to adding their separate effects.

    “Previous metaanalytic research suggested that the effects of combined treatment in depression and anxiety are the sum of the effects of psychotherapy and those of phar macotherapy 11 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Combined treatment may be the best option for treating depression in terms of both efficacy and acceptability.

    “Combined treatment may therefore be the best option for the treatment of depression both in terms of efficacy and acceptability”
    Quote in the paperSubstantial claim
29 of 29

  • The paper relies on this without support.

    No prior network meta-analysis has examined the relative effects of psychotherapies, pharmacotherapies, and their combination in adult depression.

    “No network meta-analysis has examined the relative effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression, while this is a very important clinical issue.”

  • The paper relies on this without support.

    The majority of randomized trials in this field may be prone to methodological bias.

    “The majority of randomized trials in this field may be prone to meth odological bias”

  • The paper relies on this without support.

    No information is available for different populations of patients, such as mild versus chronic or treatment-resistant depression.

    “no information is available for different popu lations of patients (e.g., mild vs. chronic or treatmentresistant depression)”

  • The paper relies on this without support.

    Acceptability of the treatments has not been examined extensively so far.

    “acceptability of the treatments has not been examined extensively so far.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Placebo-combination remission contrast is inverted

    Major

    The network ratios of 1.28 for pharmacotherapy versus placebo and 0.89 for pharmacotherapy versus psychotherapy plus placebo imply 1.44 for psychotherapy plus placebo versus placebo. The reported 0.69 is approximately the reciprocal and reverses the direction of a statistically significant comparison.

    Reported 0.69 · recomputed 1.438202

  • An included study is described as Internet treatment

    Minor

    The discussion says none of the included trials used Internet-based psychotherapy, but the cited title of included study Blom et al. 46 explicitly describes Internet treatment for depression.

  • Placebo-combination response contrast is inverted

    Minor

    The network ratios of 1.47 for combined treatment versus placebo and 1.30 for combined treatment versus psychotherapy plus placebo imply 1.13 for psychotherapy plus placebo versus placebo. The table instead reports 0.88, approximately its reciprocal.

    Reported 0.88 · recomputed 1.130769

  • Placebo-combination acceptability contrast is inverted

    Minor

    The network ratios of 1.25 for combined treatment versus placebo and 0.98 for combined treatment versus psychotherapy plus placebo imply 1.28 for psychotherapy plus placebo versus placebo. The listed 0.79 is approximately the reciprocal.

    Reported 0.79 · recomputed 1.27551

  • Psychotherapy category percentage uses the wrong count

    Minor

    The table reports 101 studies overall, but its psychotherapy categories list 48 CBT studies and 52 other studies, totaling 100. In particular, 52 of 101 is 51.5%, not the reported 52.5%.

    Reported 52.5 · recomputed 51.485149

5 of 5

No citation lists for this paper

No citation lists for this paper yet — checked again daily.

References 146 · Cited by 540

Research works printed but not linked: 15

  1. GBD2016Disease and Injury Incidence and Prevalence Collaborators. Global regional and national incidence prevalence and years lived with disability for 328 diseases and injuries for 195 countries 1990‐2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017;390:1211‐59.
  2. Cuijpers P, A meta‐analytic database of randomised trials on psychotherapies for depression.
  3. Higgins JPT, Cochrane handbook for systematic reviews of interventions version 5., 1, 0
  4. Orsini N, et al, Heterogi: Stata module to quantify heterogeneity in a meta‐analysis.
  5. Altamura M, 2017, Comparing interpersonal counseling and antidepressant treatment in primary care patients with anxious and nonanxious major depression disorder: a randomized control trial, Clin Neuropsychiatr, 14, 257
  6. Ashouri A, 2013, Effectiveness of meta‐cognitive and cognitive‐behavioral therapy in patients with major depressive disorder, Iran J Psychiatry Behav Sci, 7, 24
  7. Barrett JE, 2001, Treatment of dysthymia and minor depression in primary care: a randomized trial in patients aged 18 to 59 years, J Fam Pract, 50, 405
  8. Covi L, 1987, Cognitive behavioral group psychotherapy combined with imipramine in major depression, Psychopharmacol Bull, 23, 173
  9. Mello MF, 2001, Menezes PR. A randomized controlled trial comparing moclobemide and moclobemide plus interpersonal psychotherapy in the treatment of dysthymic disorder, J Psychother Pract Res, 10, 117
  10. Finkenzeller W, 2009, Interpersonal psychotherapy and pharmacotherapy for post‐stroke depression, Feasibility and effectiveness. Nervenarzt, 80, 805
  11. Hautzinger M, 1996, Efficacy of cognitive behavior therapy, pharmacotherapy, and the combination of both in non‐melancholic, unipolar depression, Zeitschr Klin Psychol, 25, 130
  12. Hellerstein DJ, 2001, Adding group psychotherapy to medication treatment in dysthymia: a randomized prospective pilot study, J Psychother Pract Res, 10, 93
  13. Maldonado López A., 1982, Terapia de conducta y depresión: un análisis experimental de los modelos conductual y cognitivo, Rev Psicolog Gen Aplic
  14. Maldonado López A., 1984, Un modelo de terapia cognitiva desde la perspectiva de la psicología del aprendizaje, Anuar Psicolog, 30, 75
  15. Shamsaei F, 2008, Efficacy of pharmacotherapy and cognitive therapy, alone and in combination in major depressive disorder, Hong Kong J Psychiatry, 18, 76

Authors
Cuijpers, P., Noma, H., Karyotaki, E., Vinkers, C. H., Cipriani, A., & Furukawa, T. A.
Affiliations
  • Amsterdam Public Health (NL)
  • The Institute of Statistical Mathematics (JP)
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
  • Oxford Health NHS Foundation Trust (GB)
  • Kyoto University (JP)
ORCID
Venue
World Psychiatry
Publisher
Wiley
Published
2020-01-10
Volume
19
Issue
1
Pages
92-107
ISSN
  • 1723-8617 (ISSN-L)
  • 2051-5545
DOI
10.1002/wps.20701
PMC
PMC6953550
OpenAlex
W2971304551
Cited by
540
References
146
Citations by year
2026: 65 · 2025: 93 · 2024: 102 · 2023: 111 · 2022: 67 · 2021: 62 · 2020: 37 · 2019: 2 · 2018: 1
FWCI
41.51
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • World Psychiatry (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
  • VU Research Portal (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
National Institute for Health and Care Research (RP-2017-08-ST2-006)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords
adult depression, psychotherapy, pharmacotherapy, combined psychotherapy and pharmacotherapy, treatment response, remission, treatment acceptability, chronic depression, treatment-resistant depression, depression severity, antidepressants

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