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Cognitive behavioral therapy (CBT) should be considered first-line treatment for generalized anxiety disorder in adults, according to a systematic review and network meta-analysis of 66 randomized clinical trials.

Effect size estimates on data involving 5,597 participants showed that CBT was associated with reduced anxiety symptoms compared with treatment as usual -- assessment only, with or without provision of informational material or minimal therapist contact, or both, with moderate certainty (standardized mean difference [SMD] -0.68, 95% CI -1.05 to -0.32), reported Davide Papola, MD, PhD, of Harvard Medical School in Boston, and co-authors.

Third-wave CBTs were also associated with reduced anxiety symptoms with moderate certainty when compared with treatment as usual (SMD -0.78, 95% CI -1.19 to -0.37), they noted in .

In addition, while relaxation therapy showed an association with reduced anxiety symptoms versus treatment as usual (SMD -0.54, 95% CI -1.04 to -0.05), the certainty of the evidence was low. In fact, when the authors excluded studies with a high risk of bias, relaxation therapy lost superiority over treatment as usual (SMD -0.40, 95% CI -1.15 to 0.34).

Of note, when Papola and team analyzed data on anxiety severity at 3 to 12 months after completing an intervention, traditional CBT was the only therapy that remained significantly associated with greater effectiveness over treatment as usual (SMD -0.58, 95% CI -0.93 to -0.23).

"This conclusion takes into account the trade-off between efficacy and acceptability outcomes, long-term efficacy, and certainty in the level of evidence," Papola told MedPage Today in an email.

Generalized anxiety disorder is one of the most common mental conditions in adults. While psychotherapies are often recommended, first-line treatment needs to be clarified, the authors noted.

Papola said that the data supported clinical guidelines for the treatment of adults with generalized anxiety disorder, which recommend CBT.

"There is strong evidence that CBT is equally effective when delivered in individual, group, or guided self-help formats," he explained. "Policymakers should inform service organizations according to a stepped-care approach, where people are first offered flexible and low-cost options -- guided self-help programs, videoconferencing -- followed by more intensive and structured therapies -- face-to-face psychotherapy, medication therapy -- as needed."

Papola also noted that "it is possible to argue that third-wave CBT can be considered a solid alternative to traditional CBT, at least in the short term. More research is needed to clarify whether the beneficial effects of third-wave CBT are as long-lasting as those of traditional CBT."

There has been increased interest in third-wave CBTs, including , , , and , over time, which has led to more research in recent years.

Papola said the study findings also suggest that relaxation therapy could be valuable when incorporated into CBT protocols rather than implemented as a stand-alone intervention.

To conduct this systematic review and meta-analysis, two independent investigators searched MEDLINE, Embase, PsycINFO, and the Cochrane Register of Controlled Trials from database inception to Jan. 1, 2023, and identified 66 randomized clinical trials of psychotherapies for adults with generalized anxiety disorder. Mean age of the participants was 42.2 years, and 70.9% were women.

The trials compared eight psychotherapies against one another, along with two control conditions -- treatment as usual and waiting list.

Relative risks for all-cause discontinuation -- an indication of acceptability -- showed no differences compared with treatment as usual for all psychotherapies; for example, the relative risk was 1.07 (95% CI 0.73-1.57) for CBT versus treatment as usual.

Papola noted that there were limitations to the analysis, including that a third of the studies were considered to have a high risk of bias and two-thirds did not analyze data according to intention-to-treat principles. He also said that their results are only informative for prototypical patients because they based the analysis on aggregate-level data.

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