Efficacy and Acceptability Comparisons of Cognitive Behavior Therapy, Drugs, and Their Combination for Panic Disorder in Adults: A Network Meta-Analysis

Background: Panic disorder (PD) is common and burdensome in general population. Patients with PD are among highest users of health-care services. Cognitive behavior therapy, drugs and their combination are its treatment of choice, but have never been evaluated in a comprehensive network meta-analysis. We aimed to compare and rank these interventions for the acute treatment of adults with PD. Methods: Electronic databases were searched for randomized controlled clinical trials (RCTs) of the use of 22 oral drugs, CBT, CBT combined with any drug, or placebo in the acute treatment of adults with PD diagnosed according to standard operationalized criteria from their inception up to May 26, 2019. The primary outcomes were efficacy (remission rate) and acceptability (treatment discontinuations due to any cause). The risk of bias of the studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. We estimated summary odds ratios for the primary outcomes using pairwise and network meta-analysis with random effects. Findings: We identified 6585 reports that included 68 full-text RCTs involving 12534 patients. In terms of efficacy, 13 (68%) of 19 interventions were associated with higher remission rates than those of for placebo, with ORs ranging from 2.1 (95% credible interval [CrI] = 1.1 to 4.0) for sertraline to 13 (CrI = 4.5 to 44) for CBT combined with any drug. Regarding acceptability, alprazolam, imipramine, and etizolam were associated with lower dropout rates, with ORs ranging from 0.23 (CrI = 0.15 to 0.33) for alprazolam to 0.076 (CrI = 0.0021 to 0.77) for etizolam. Most of the differences between the other interventions were unclear. In head-to-head analyses, CBT combined with any drug was more effective than the other interventions, but it was no associated with an improvement in acceptability (OR = 0.12 to 0.219). Interpretation: CBT combined with any drug was more effective than the other interventions analyzed in this study. CBT alone did not differ significantly from other drugs alone. We found that most drugs — and especially selective serotonin-reuptake inhibitors — are effective against PD, but they exhibit different acceptability and tolerability profiles. Funding Statement: This work was supported by the National Natural Science Foundation of China (No. 81771471), and the Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University, China (No.XJTU1AF-CRF-2016-024). Declaration of Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.