Cognitive-behaviour therapy (CBT) for panic disorder may consist of different combinations of several therapeutic components such as relaxation, breathing retraining, cognitive restructuring, interoceptive exposure and/or in vivo exposure. It is therefore important both theoretically and clinically to examine whether specific components of CBT or their combinations are superior to others in the treatment of panic disorder. Component network meta-analysis (NMA) is an extension of standard NMA that can be used to disentangle the treatment effects of different components included in composite interventions. We searched MEDLINE, EMBASE, PsycINFO and Cochrane Central, with supplementary searches of reference lists and clinical trial registries, for all randomized controlled trials comparing different CBT-based psychological therapies for panic disorder with each other or with control interventions. We applied component NMA to disentangle the treatment effects of different components included in these interventions. After reviewing 2526 references, we included 72 studies with 4064 participants. Interoceptive exposure and face-to-face setting were associated with better treatment efficacy and acceptability. Muscle relaxation and virtual-reality exposure were associated with significantly lower efficacy. Components such as breathing retraining and in vivo exposure appeared to improve treatment acceptability while having small effects on efficacy. The comparison of the most v. the least efficacious combination, both of which may be provided as ‘evidence-based CBT,’ yielded an odds ratio for the remission of 7.69 (95% credible interval: 1.75 to 33.33). Effective CBT packages for panic disorder would include face-to-face and interoceptive exposure components, while excluding muscle relaxation and virtual-reality exposure.

There is no high-quality, unequivocal evidence to support one psychological therapy over the others for the treatment of panic disorder with or without agoraphobia in adults. However, the results show that CBT - the most extensively studied among the included psychological therapies - was often superior to other therapies, although the effect size was small and the level of precision was often insufficient or clinically irrelevant. In the only two studies available that explored PD, this treatment showed promising results, although further research is needed in order to better explore the relative efficacy of PD with respect to CBT. Furthermore, PD appeared to be the best tolerated (in terms of ST-dropouts) among psychological treatments. Unexpectedly, we found some evidence in support of the possible viability of non-specific supportive psychotherapy for the treatment of panic disorder; however, the results concerning SP should be interpreted cautiously because of the sparsity of evidence regarding this treatment and, as in the case of PD, further research is needed to explore this issue. Behaviour therapy did not appear to be a valid alternative to CBT as a first-line treatment for patients with panic disorder with or without agoraphobia.

Many healthcare interventions are complex, consisting of multiple, possibly interacting, components. Several methodological articles addressing complex interventions in the meta-analytical context have been published. We hereby provide an overview of methods used to evaluate the effects of complex interventions with meta-analytical models. We summarized the methodology, highlighted new developments, and described the benefits, drawbacks, and potential challenges of each identified method. We expect meta-analytical methods focusing on components of several multicomponent interventions to become increasingly popular due to recently developed, easy-to-use, software tools that can be used to conduct the relevant analyses. The different meta-analytical methods are illustrated through two examples comparing psychotherapies for panic disorder.

BackgroundPanic disorder is characterised by the presence of recurrent unexpected panic attacks, discrete periods of fear or anxiety that have a rapid onset and include symptoms such as racing heart, chest pain, sweating and shaking. Panic disorder is common in the general population, with a lifetime prevalence of 1-4%. A previous Cochrane meta-analysis suggested that psychological therapy (either alone or combined with pharmacotherapy) can be chosen as a first-line treatment for panic disorder with or without agoraphobia. However, it is not yet clear whether certain psychological therapies can be considered superior to others. To answer this question, in this review we performed a network meta-analysis (NMA), in which we compared eight different forms of psychological therapy and three forms of a control condition.

IntroductionPsychotherapy is a complex intervention, consisting of various components and being implemented flexibly in consideration of individual patient’s characteristics. It is then of utmost importance to know which of the various components or combinations thereof are more efficacious, what their specific effect sizes are and which types of patients may benefit more from different components or their combinations.Methods and analysisInternet-delivered cognitive–behavioural therapy (iCBT) offers a unique opportunity to systematically review and quantitatively disentangle the efficacy of various components because, unlike face-to-face cognitive–behavioural therapy, it allows identification of constituent components that are actually delivered to patients. We will systematically identify all randomised controlled trials that compared any form of iCBT against another form or a control intervention in the acute phase treatment of adult depression. We will apply component network meta-analysis (cNMA) to dismantle efficacy of individual components. We will use individual participant data in the cNMA to identify participant-level prognostic factors and effect modifiers for different components.Ethics and disseminationThe investigators of the primary trials will have obtained ethical approval for the data used in the present study and for sharing the data, if this was necessary, according to local requirements and was not covered from the initial ethic assessment. Results from this study will be published in peer-reviewed journals and presented at relevant conferences.PROSPERO registration numberCRD42018104683.