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Cited by 151Anxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesPsychotherapy Techniques and ApplicationsDigital Mental Health Interventions

Psychological and pharmacological treatments for generalized anxiety disorder (GAD): a meta-analysis of randomized controlled trials

Open access
Carl, Emily, Witcraft, Sara M., Kauffman, Brooke Y., Gillespie, Eilis M., Becker, Eni S., Cuijpers, Pim, Van Ameringen, Michael, Smits, Jasper A. J. +1 more·2020·Cognitive Behaviour Therapy
DOI 10.1080/16506073.2018.1560358PMC PMC7063818
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Abstract

The purpose of this meta-analysis was to provide updated pooled effect sizes of evidence-based psychotherapies and medications for generalized anxiety disorder (GAD) and to investigate potential moderators of outcomes. Seventy-nine randomized controlled trials (RCT) including 11,002 participants with a diagnosis of GAD were included in a meta-analysis that tested the efficacy of psychotherapies or medications for GAD. Psychotherapy showed a medium to large effect size (g = 0.76) and medication showed a small effect size (g = 0.38) on GAD outcomes. Psychotherapy also showed a medium effect on depression outcomes (g = 0.64) as did medications (g = 0.59). Younger age was associated with a larger effect size for psychotherapy (p < 0.05). There was evidence of publication bias in psychotherapy studies. This analysis found a medium to large effect for empirically supported psychotherapy interventions on GAD outcomes and a small effect for medications on GAD outcomes. Both groups showed a medium effect on depression outcomes. Because medication studies had more placebo control conditions than inactive conditions compared to psychotherapy studies, effect sizes between the domains should not be compared directly. Patient age should be further investigated as a potential moderator in psychotherapy outcomes in GAD.

Integrity signals

Registry

Crossref · 10.1080/16506073.2018.1560358

Cites

114 of 114 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 17 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Psychotherapy studies showed significant heterogeneity (I2=54.90, Q=84.25, p<0.001).

    “This was also true when psychotherapy (I2 = 54.90, Q = 84.25, p < 0.001) and medication studies (I2 = 54.26, Q = 163.72, p < 0.001) were considered separately.”
    Quote in the paperSubstantial claim
  • Findingown data

    Pharmacotherapy outperformed control conditions on primary GAD outcomes at posttreatment, with a small effect size (g=0.38, 95% CI 0.30-0.47, p<0.001).

    “medication showed a small effect size (g = 0.38) on GAD outcomes”
    • Also stated in: § Efficacy on primary and secondary outcomes · plain
      “Consistent with prediction, pharmacotherapy outperformed control conditions on primary outcome measures at posttreatment with a small effect size (g = 0.38, 95% CI: 0.30–0.47, p < 0.001).”
    Quote in the paperSubstantial claim
  • Findingown data

    Lower mean age predicted a larger treatment effect size in psychotherapy (β = −0.013, p < 0.05).

    “Younger age was associated with a larger effect size for psychotherapy (p < 0.05).”
    • Also stated in: § Moderators · plain
      “A lower mean age predicted a larger treatment effect size in psychotherapy (β = −0.013, p < 0.05).”
    • Also stated in: § Main findings · plain
      “younger age of the study sample was associated with higher effect size in psychotherapy studies.”
    Quote in the paperSubstantial claim
  • Findingown data

    Pharmacotherapy outperformed control conditions on secondary depression outcomes at posttreatment, with a medium effect size (g=0.59, 95% CI 0.21-0.97, p<0.01).

    “as did medications (g = 0.59)”
    • Also stated in: § Efficacy on primary and secondary outcomes · plain
      “Pharmacotherapy outperformed control conditions on secondary outcome measures at posttreatment with a medium effect size (g = 0.59, 95% CI: 0.21–0.97, p < 0.01).”
    Quote in the paperSubstantial claim
  • Findingown data

    In psychotherapy studies, pill placebo-controlled comparisons had effect size g=1.44 (n=3, 95% CI 0.94-1.94, p<0.001).

    “Within psychotherapy comparisons, pill placebo-controlled studies had the highest effect size (n = 3, g = 1.44, 95% CI: 0.94–1.94, p < 0.001), followed by WL controls (n = 22, g = 0.90, 95% CI: 0.73–1.08, p < 0.001), psychological placebo (n = 10, g = 0.47, 95% CI: 0.25–0.69, p < 0.001), and TAU (n = 5, g = 0.38, 95% CI: 0.05–0.71, p < 0.05; in Wetherell et al., 2003, the psychological placebo and”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 12
  • May combine two claims. 12
  • The quote only partly states this claim. 1

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

    Findingown data

    The psychotherapy vs control primary outcome analysis included 39 comparisons.

    “This analysis included 39 comparisons.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The pharmacotherapy vs control secondary outcome analysis included 11 comparisons.

    “This analysis included 11 comparisons.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Distribution of number of quality criteria met: 6 met 0, 27 met 1, 21 met 2, 10 met 3, 15 met all 4.

    “Six studies met 0 study quality criteria, 27 studies met one criterion, 21 studies met two criteria, 10 studies met three criteria, and 15 studies met all four criteria.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The psychotherapy vs control secondary outcome analysis included 29 comparisons.

    “This analysis included 29 comparisons.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The pharmacotherapy vs control primary outcome analysis included 43 comparisons.

    “This analysis included 43 comparisons.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    At follow-up, evidence-based psychotherapies outperformed control conditions on secondary depression outcomes with small effect size g=0.27 (95% CI 0.06-0.49, p=0.01), based on 8 comparisons.

    “At follow-ups, 8 comparisons showed that evidence-based psychotherapies outperformed control conditions on secondary outcome measures at follow-ups with a small effect size (g = 0.27, 95% CI: 0.06–0.49, p = 0.01).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    No significant relationship was found between effect size and treatment dose, treatment quality, year of publication, fixed vs flexible dose, percent comorbidity, percent female, or pretreatment severity (all p>0.10).

    “There was no significant relationship between effect size and treatment dose (number of sessions or medication dosage), treatment quality, year of publication, fixed versus flexible dose, percent comorbidity, percent female, or pretreatment severity (all p > 0.10).”
    Quote in the paperSubstantial claim

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

    Findingown data

    Control conditions across included studies were categorized as pill placebo (n=43), waitlist (n=22), psychological placebo (n=10), and treatment as usual (n=5).

    “Control conditions were categorized as pill placebo (n = 43), waitlist (WL; n = 22), psychological placebo (n = 10), or treatment as usual (TAU; n = 5), with one study (Wetherell, Gatz, & Craske, 2003) including both a WL and psychological placebo group.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Pharmacotherapy studies showed no evidence of funnel plot asymmetry or trim-and-fill adjustment.

    “A funnel plot in pharmacotherapy studies did not reveal asymmetry according to Egger’s intercept and a trim and fill procedure did not impute any studies or adjust the effect size estimate.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among included studies, 30 had low risk of bias for sequence generation, 22 for allocation concealment, 66 for blind assessors, and 39 for incomplete outcome data.

    “Of the 79 included studies, 30 had low bias for sequence generation, 22 qualified for low bias for allocation concealment, 66 qualified for low bias for blind assessors, and 39 qualified for low bias for incomplete outcome data.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was evidence of publication bias in psychotherapy studies, with funnel plot asymmetry (Egger's intercept=1.93, p<0.01) and trim-and-fill imputing 5 studies to adjust the effect size estimate to 0.66.

    “There was evidence of publication bias in psychotherapy studies.”
    • Also stated in: § Publication bias: “the file drawer problem” · plain
      “A funnel plot revealed asymmetry in psychotherapy studies (Egger’s intercept = 1.93, p < 0.01; Figure 3), and the Duval and Tweedie (2000) trim and fill procedure imputed 5 studies for an adjusted effect size estimate of 0.66.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    If pill placebo is a more stringent control than waitlist, it would contribute to the apparent difference in effect size between psychotherapy and pharmacotherapy.

    “If a pill placebo is a much more stringent control condition than WL, this would have contributed to this apparent difference in effect size.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Nonsignificant studies tend not to be published, which may lead to overestimation of true effect sizes.

    “Because nonsignificant studies tend not to be published, there may be a discrepancy in results between the studies that are retrievable and all studies that have been conducted. Unavailable negative results may lead to overestimate the true effect size. Rosenthal and colleagues have termed this phenomenon “the file drawer problem” (Rosenthal, 1991).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rosenthal, 1991

      Not checked in the free run.

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

    Premisecitation

    A recent systematic review found little evidence for demographic variables, baseline symptom severity, or comorbidity as moderators of anxiety disorder treatment.

    “A recent systematic review investigated a large number of potential treatment moderators of treatment for anxiety disorders and found little evidence for demographic variables, baseline symptom severity, or comorbidity as moderators (Schneider, Arch, & Wolitzky-Taylor, 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Schneider et al., 2015

      Not checked in the free run.

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

    Study design and conductcitation

    Included studies' quality was rated using four Cochrane Risk of Bias items (sequence generation, allocation concealment, blind assessors, incomplete outcome data).

    “The quality of the studies that were included was rated using four items from the Cochrane Risk of Bias Tool (Higgins & Green, 2011): (1) adequately random sequence generation for group assignment, (2) concealment of allocation to conditions, (3) blind assessors, and (4) dealing with incomplete outcome data.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Higgins & Green, 2011

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The finding that pill-placebo-controlled psychotherapy studies had higher effect sizes than waitlist-controlled studies is likely a fluke and underpowered, because a larger meta-analysis found larger effects for waitlist than pill placebo.

    “Although in this analysis the three pill placebo controlled psychotherapy studies had a higher effect size than waitlist controlled studies, this is likely a fluke and underpowered, as a larger meta-analysis of CBT for anxiety disorders showed that effects were large for waitlist conditions and small to medium for pill placebo comparisons (n = 144 trials; Cuijpers et al., 2016).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Cuijpers et al., 2016

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The prior systematic review was not specific to GAD, included only 24 studies comparing at least two active treatments, and did not use meta-analytic techniques.

    “However, this study was not specific to GAD, only included 24 studies that compared at least two active treatments, and did not employ meta-analytic techniques.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Schneider et al., 2015

      Not checked in the free run.

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

    Premisecitation

    Prior evidence suggests older age may be associated with worse GAD treatment outcomes.

    “there is some evidence that older age might lead to worse GAD treatment outcomes (Gonçalves & Byrne, 2012; Gould, Coulson, & Howard, 2012; Hendriks, Oude Voshaar, Keijsers, Hoogduin, & Van Balkom, 2008; Pinquart & Duberstein, 2007; Wetherell et al., 2013).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Gonçalves & Byrne, 2012

      Not checked in the free run.

    • cites Gould et al., 2012

      Not checked in the free run.

    • cites Hendriks et al., 2008

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Random effects analyses were appropriate and moderator analyses justified due to heterogeneity.

    “Therefore, random effects analyses were most appropriate and moderator analyses were justified.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Most moderators did not show evidence of influence, corroborating previous conclusions.

    “Most moderators did not show evidence of influence. This corroborates previous conclusions (Schneider et al., 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Schneider et al., 2015

      Not checked in the free run.

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

    Study design and conductown data

    Outliers were removed from moderator analyses because of their substantial leverage and influence on regression results, despite minor effect on pooled effect size estimates.

    “Although outliers had minor effect on pooled effect size estimates, they were removed from moderator analyses due to their substantial leverage and influence on regression results.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The analysis used a random effects model because considerable heterogeneity was expected from patient and treatment variability.

    “Because we expected considerable heterogeneity due to patient and treatment variability, we used the random effects model in all analyses.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The finding that younger age is associated with better psychotherapy outcomes is consistent with prior findings that anxiety disorder treatments are less effective for older people.

    “Although this is not direct evidence that younger age was the cause of receptiveness to psychotherapy, this is consistent with findings from a number of investigators that treatments for anxiety disorders are not as effective for older people relative to younger people (Gonçalves & Byrne, 2012; Gould et al., 2012; Hendriks et al., 2008; Pinquart & Duberstein, 2007; Wetherell et al., 2013).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Gonçalves & Byrne, 2012

      Not checked in the free run.

    • cites Gould et al., 2012

      Not checked in the free run.

    • cites Hendriks et al., 2008

      Not checked in the free run.

23 of 23

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?

  • CBT for generalized anxiety disorder also shows strong efficacy for comorbid anxiety and depressive disorders.

    “CBT for GAD also has shown strong efficacy for comorbid anxiety and depressive disorders [10,12].”

    From Psychotherapeutic treatments for generalized anxiety disorder: cognitive and behavioral therapies, enhancement strategies, and emerging efforts (2022) · cites this paper as [10]

    The Results (Efficacy on primary and secondary outcomes; page not provided) report that evidence-based psychotherapies for GAD improved GAD symptoms and secondary depressive symptoms compared with controls. The paper does not establish strong efficacy specifically for CBT in treating comorbid anxiety and depressive disorders: it pools psychotherapies, measures depressive symptoms rather than depressive-disorder outcomes, and does not report treatment effects on other comorbid anxiety disorders. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • CBT for generalized anxiety disorder yields greater improvement than psychological placebo, with a reported effect size of g = 0.47 (95% CI 0.25 to 0.69).

    “psychological placebo (g = 0.47, 95% CI [0.25, 0.69])”

    From Psychotherapeutic treatments for generalized anxiety disorder: cognitive and behavioral therapies, enhancement strategies, and emerging efforts (2022) · cites this paper as [10]

    The Results (Efficacy on primary and secondary outcomes; page unavailable) report that psychotherapy outperformed psychological placebo on GAD outcomes, with g = 0.47 (95% CI: 0.25–0.69). The Methods (Study selection; page unavailable) include CBT alongside other psychotherapies, so this pooled estimate is not identified as a CBT-specific effect. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • CBT for generalized anxiety disorder yields greater improvement than treatment as usual, with a reported effect size of g = 0.38 (95% CI 0.05 to 0.71).

    “treatment as usual (TAU; g = 0.38, 95% CI [0.05, 0.71]) [10]”

    From Psychotherapeutic treatments for generalized anxiety disorder: cognitive and behavioral therapies, enhancement strategies, and emerging efforts (2022) · cites this paper as [10]

    The Results section (Efficacy on primary and secondary outcomes; page unavailable) reports that evidence-based psychotherapies outperformed treatment as usual on primary GAD outcomes, with g = 0.38 and 95% CI 0.05–0.71. It reports this estimate for psychotherapy comparisons, not specifically for CBT, so the CBT-specific attribution is not established. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • CBT for generalized anxiety disorder yields greater improvement than pill placebo, with a reported effect size of g = 1.44 (95% CI 0.94 to 1.94).

    “A meta-analysis found that CBT for GAD led to greater improvement than pill placebo (g = 1.44, 95% CI [0.94, 1.94])”

    From Psychotherapeutic treatments for generalized anxiety disorder: cognitive and behavioral therapies, enhancement strategies, and emerging efforts (2022) · cites this paper as [10]

    The Results section reports greater improvement on primary GAD outcomes in three pill-placebo-controlled psychotherapy comparisons, with g = 1.44 (95% CI 0.94–1.94). It labels this a result for evidence-based psychotherapy, not specifically CBT, so the treatment-specific wording is not established by our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • A recent meta-analysis could not find any rigorous studies assessing outcome following termination of pharmacotherapy for generalized anxiety disorder.

    “In fact, a recent meta-analysis could not find any rigorous studies that assessed outcome following termination of pharmacotherapy for GAD [10].”

    From Psychotherapeutic treatments for generalized anxiety disorder: cognitive and behavioral therapies, enhancement strategies, and emerging efforts (2022) · cites this paper as [10]

    The Results (Efficacy on primary and secondary outcomes; page unavailable) say no pharmacotherapy studies with follow-up data on the primary GAD outcome were available for the meta-analysis. That supports the absence of usable follow-up evidence in its analysis, but not the broader claim that no rigorous studies assessed outcomes after pharmacotherapy ended: the Study selection section says relapse-prevention studies were excluded. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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.

  • Study-quality tallies differ by two criteria

    Minor

    The four criterion-specific counts total 157. The distribution of studies by number of criteria met implies 159, so the two summaries cannot both be correct.

  • Medication heterogeneity does not match the comparison count

    Minor

    For 43 comparisons, the reported Q of 163.72 gives I2 = (163.72 − 42) / 163.72 = 74.35%, not 54.26%. The reported I2 instead implies approximately 76 comparisons.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 11

  1. *Bakhshani N., 2007, International Journal of Medical Sciences
  2. 10.1016/S0005-7894(05)80221-7 · DOI · Paper page
  3. Beck A. T., 1996, BDI-II, Beck Depression Inventory: Manual
  4. 10.1037//0022-006X.55.6.883 · DOI
  5. 10.1001/jama.283.23.3082 · DOI
  6. 10.137/journal.pone.0028079
  7. 10.1016/j.anxdis.2015.10.006 · DOI
  8. 10.1007/s0021300507 · DOI
  9. *Power K. G., 1990, The British Journal of General Practice : the Journal of the Royal College of General Practitioners, 40, 289
  10. 10.1371/journal.pone.001942 · DOI
  11. 10.3760/cma.j.issn.0366-6999.2011.20.010 · DOI

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Authors
Carl, E., Witcraft, S. M., Kauffman, B. Y., Gillespie, E. M., Becker, E. S., Cuijpers, P., Van Ameringen, M., Smits, J. A. J., & Powers, M. B.
Affiliations
  • The University of Texas at Austin (US)
  • University of Mississippi (US)
  • University of Houston (US)
  • Ollscoil na Gaillimhe – University of Galway (IE)
  • Radboud University Nijmegen (NL)
  • Vrije Universiteit Amsterdam (NL)
  • Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
  • Baylor University Medical Center (US)
Corresponding author
Carl, Emily
ORCID
Venue
Cognitive Behaviour Therapy
Publisher
Informa UK Limited
Published
2019-02-14
Volume
49
Issue
1
Pages
1-21
ISSN
  • 1650-6073 (ISSN-L)
  • 1651-2316
DOI
10.1080/16506073.2018.1560358
PMC
PMC7063818
OpenAlex
W2912152524
Cited by
151
References
114
Citations by year
2026: 21 · 2025: 31 · 2024: 22 · 2023: 26 · 2022: 21 · 2021: 16 · 2020: 13 · 2019: 1
FWCI
1.91
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Cognitive Behaviour Therapy (publishedVersion)
  • PubMed (publishedVersion)
  • VU Research Portal (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
National Institute on Drug Abuse (F31DA046127)
Topics
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
  • Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
  • Social Sciences › Psychology › Applied Psychology › Digital Mental Health Interventions
Keywords
generalized anxiety disorder, psychotherapy, pharmacotherapy, antidepressants, depression outcomes, treatment efficacy, age as moderator, publication bias
MeSH terms
Anxiety Disorders, Humans, Outcome and Process Assessment, Health Care, Psychotherapy, Anti-Anxiety Agents, Randomized Controlled Trials as Topic

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