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. 2024 Mar 1;81(3):250-259.
doi: 10.1001/jamapsychiatry.2023.3971.

Psychotherapies for Generalized Anxiety Disorder in Adults: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials

Davide Papola  1   2   3 , Clara Miguel  4   5 , Mariacristina Mazzaglia  2   3 , Pamela Franco  6   7 , Federico Tedeschi  2   3 , Sara A Romero  1 , Anushka R Patel  8 , Giovanni Ostuzzi  2   3 , Chiara Gastaldon  2   3 , Eirini Karyotaki  4   5 , Mathias Harrer  9 , Marianna Purgato  2   3 , Marit Sijbrandij  4   5 , Vikram Patel  1 , Toshi A Furukawa  10 , Pim Cuijpers  4   5 , Corrado Barbui  2   3
Affiliations

Psychotherapies for Generalized Anxiety Disorder in Adults: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials

Davide Papola et al. JAMA Psychiatry. .

Erratum in

Abstract

Importance: Generalized anxiety disorder (GAD) is one of the most common mental disorders in adults. Psychotherapies are among the most recommended treatments for GAD, but which should be considered as first-line treatment needs to be clarified.

Objective: To use a network meta-analysis to examine the short- and long-term associations of different psychotherapies with outcomes of effectiveness and acceptability in adults with GAD.

Data sources: MEDLINE, Embase, PsycINFO, and the Cochrane Register of Controlled Trials were searched from database inception to January 1, 2023, to identify randomized clinical trials (RCTs) of psychotherapies for adults with GAD.

Study selection: RCTs comparing any type of psychotherapy against another or with a control condition for the treatment of adults (≥18 years, both sexes) with a primary diagnosis of GAD were eligible for inclusion.

Data extraction and synthesis: This study followed Cochrane standards for extracting data and assessing data quality and used the PRISMA guideline for reporting. Risk of bias of individual studies was assessed using the second version of the Cochrane risk of bias tool, and the Confidence in Network Meta-Analysis was used to rate the certainty of evidence for meta-analytical results.

Main outcomes and measures: Eight psychotherapies were compared against one another and with 2 control conditions. Primary outcomes were severity of GAD symptoms and acceptability of the psychotherapies. Random-effects model pairwise and network meta-analyses were conducted. For effectiveness, standardized mean differences (SMDs) were pooled, and for acceptability, relative risks with 95% CIs were calculated.

Results: Data from 65 RCTs were included. Effect size estimates on data from 5048 participants (mean [SD], 70.9% [11.9%] women; mean [SD] age, 42.2 [12.5] years) suggested that third-wave cognitive behavior therapies (CBTs) (SMD, -0.76 [95% CI, -1.15 to -0.36]; certainty, moderate), CBT (SMD, -0.74 [95% CI, -1.09 to -0.38]; certainty, moderate), and relaxation therapy (SMD, -0.59 [95% CI, -1.07 to -0.11]; certainty, low) were associated with reduced GAD symptoms vs treatment as usual. Relative risks for all-cause discontinuation (indication of acceptability) signaled no differences compared with treatment as usual for all psychotherapies (eg, relative risk, 1.04 [95% CI, 0.64-1.67] for CBT vs treatment as usual). When excluding studies at high risk of bias, relaxation therapy lost its superiority over treatment as usual (SMD, -0.47; 95% CI, -1.18 to 0.23). When considering anxiety severity at 3 to 12 months after completion of the intervention, only CBT remained significantly associated with greater effectiveness than treatment as usual (SMD, -0.60; 95% CI, -0.99 to -0.21).

Conclusions and relevance: Given the evidence in this systematic review and network meta-analysis for its associations with both acute and long-term effectiveness, CBT may represent the first-line therapy of GAD. Third-wave CBTs and relaxation therapy were associated with short-term effectiveness and may also be offered.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Harrer reported being a part-time employee of GET.ON Institute for Online Health Training GmbH and HelloBetter. Dr Sijbrandij reported receiving grants from the European Union outside the submitted work. Dr Furukawa reported receiving personal fees from Boehringer Ingelheim, DT Axis, Kyoto University Original, Shionogi, and Sony outside the submitted work; receiving grants from Shionogi outside the submitted work; and holding patents for Kokoro-app licensed to Mitsubishi-Tanabe. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Network Plot of Evidence for Effectiveness
Line thickness is proportional to the precision of each direct estimate; circle size is proportional to the number of studies including that treatment. Gray circles represent psychotherapies; orange circles, controls. CBT indicates cognitive behavior therapy.
Figure 2.
Figure 2.. Net League Table of Head-to-Head Comparisons
Standardized mean differences and 95% CIs are reported for the primary outcome of effectiveness (light blue), with standardized mean differences lower than 0 favoring the column-defining treatment. Relative risks and 95% CIs are reported for the primary outcome of acceptability (light red), with relative risk lower than 1 favoring the column-defining treatment. Green represents interventions; white (Treatment as usual, Waiting list), controls. Statistically significant results are in dark red and blue boxes. CBT indicates cognitive behavior therapy.
Figure 3.
Figure 3.. Forest Plots for Effectiveness and Acceptability, Comparing Each Psychotherapy With Treatment as Usual (TAU)
Reference treatment for both plots is TAU. CBT represents cognitive behavior therapy.
See this image and copyright information in PMC

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References

    1. Cuijpers P, Cristea IA, Karyotaki E, Reijnders M, Huibers MJ. How effective are cognitive behavior therapies for major depression and anxiety disorders? a meta-analytic update of the evidence. World Psychiatry. 2016;15(3):245-258. doi:10.1002/wps.20346 - DOI - PMC - PubMed
    1. Bandelow B, Sagebiel A, Belz M, Görlich Y, Michaelis S, Wedekind D. Enduring effects of psychological treatments for anxiety disorders: meta-analysis of follow-up studies. Br J Psychiatry. 2018;212(6):333-338. doi:10.1192/bjp.2018.49 - DOI - PubMed
    1. Cuijpers P, Sijbrandij M, Koole S, Huibers M, Berking M, Andersson G. Psychological treatment of generalized anxiety disorder: a meta-analysis. Clin Psychol Rev. 2014;34(2):130-140. doi:10.1016/j.cpr.2014.01.002 - DOI - PubMed
    1. Rouse B, Chaimani A, Li T. Network meta-analysis: an introduction for clinicians. Intern Emerg Med. 2017;12(1):103-111. doi:10.1007/s11739-016-1583-7 - DOI - PMC - PubMed
    1. Cuijpers P, Karyotaki E, Reijnders M, Ebert DD. Was Eysenck right after all? a reassessment of the effects of psychotherapy for adult depression. Epidemiol Psychiatr Sci. 2019;28(1):21-30. doi:10.1017/S2045796018000057 - DOI - PMC - PubMed

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