Davide Papola, MD, PhD: CBT Should Be A First-Line Treatment for Generalized Anxiety Disorder


Papola comments on the study he led which found that cognitive behavior therapy is the most effective form of treatment for GAD.

Davide Papola, MD, PhD: CBT Should Be A First-Line Treatment for Generalized Anxiety Disorder

Credit: Davide Papola

A recent systematic review and meta-analyses, led by Davide Papola, MD, PhD, of the department of global health and social medicine at Harvard Medical School, found that cognitive behavior therapy (CBT) is the most effective psychotherapy for generalized anxiety disorder (GAD).

Other than CBT, the study compared 7 other psychotherapies—behavior therapy, cognitive restructuring, psychoeducation, psychodynamic therapy, relaxation therapy, supportive psychotherapy, and third-wave CBTs. Third-wave CBTs and relaxation therapy performed nearly as well as CBT—all exceeding other treatments for effectiveness—but the same was not true after Papola and the rest of his team tested for biases. After the high-risk bias examination, the investigators found that CBT was the most effective treatment for GAD.

In an interview with HCPLive, Papola discussed his thoughts on the different forms of GAD treatment, challenges faced during the study, and areas of future research.

HCPLive: What would you consider the most important takeaway of the study for clinicians?

Papola: The main takeaway is that CBT should be considered a first-line treatment for adults with generalized anxiety disorder. This conclusion takes into account the trade-off between efficacy and acceptability outcomes, long-term efficacy, and certainty in the level of evidence.

HCPLive: What is your view on the treatment methods of relaxation therapy and third-wave CBTs?

Papola: In the short term, relaxation was superior to usual care, but this was no longer the case in analyses of longer-term outcomes. The level of certainty of the evidence for relaxation therapy in the main analysis was also judged to be low, mainly because of concerns about statistical heterogeneity. Unfortunately, the type of analyses we conducted were not designed to elucidate the mechanisms of change underlying the different psychotherapies under scrutiny, and more research is needed in this area. It is important to note, however, that the evidence we present should not be considered definitive, and the evidence for relaxation therapy will continue to be shaped by future randomized controlled trials.

HCPLive:Did you face any challenges while doing the study?

Papola: Conducting a meta-analysis, especially a network meta-analysis, is always challenging because investigators must balance clinical and statistical needs. Although I suspect that there is no [network meta-analysis] that fully satisfies both needs simultaneously, I am confident that our results are statistically sound because our network showed stability while maintaining the transitivity assumption.

On the other hand, moderate to high levels of heterogeneity were found. From the clinical side, psychotherapy protocols of different therapies often share similar theoretical background and active components, and in selected cases it was difficult to draw straight lines between different types of psychotherapy. To maximize the reliability of our findings, two independent researchers classified the psychotherapies, and assistance was sought directly from the study authors when needed.

HCPLive: Can you discuss any future research that you think might need to be conducted?

Papola: Future research should focus on components of psychotherapies (i.e., active ingredients) and analyses of individual participant data. Indeed, our analysis was based on aggregate-level data, and the results of the present investigation are only informative for prototypical patients. By working with individual participant data, it will be possible to identify the impact of participant-level prognostic factors (baseline characteristics that predict outcome regardless of intervention) and effect modifiers (covariates that predict differential response to treatments) on intervention outcomes. In this way, it will be possible to personalize research findings to determine which types of patients may benefit more from different psychotherapies (or psychotherapy components). As a result, it will be possible to tailor interventions to patients' preferences and individual characteristics.


Papola D, Miguel C, Mazzaglia M, et al. Psychotherapies for Generalized Anxiety Disorder in Adults: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials [published online ahead of print, 2023 Oct 18]. JAMA Psychiatry. 2023;10.1001/jamapsychiatry.2023.3971. doi:10.1001/jamapsychiatry.2023.3971

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