In the search for systematic reviews, we identified 2,828 records after removal of duplicates. We excluded 2,735 records by screening of title and abstracts and assessed 93 records for inclusion by full-text review. We initially included one systematic review concerning pharmacological treatment of patients with adjustment disorder [46], and in our supplementary search included a further three reviews, which concerned pharmacological treatment of patients with generalized anxiety disorder [60], patients with social anxiety disorder [77], and patients with panic disorder [5]. From these systematic reviews, we included a total of 30 primary RCTs that met our adjusted inclusion criteria.

In the search for primary studies (performed 11 February 2022 and updated 8 September 2022), we identified 3,419 records after removal of duplicates of which 28 were assessed for inclusion by full-text review and four RCTs were included.

In total, 34 RCTs (43 publications and 1 unpublished trial) comprising a total of 7044 patients were included. See PRISMA flowchart of the trial selection process (Supplementary Fig. S1A, B). A table of included trials are listed in Supplementary Table S1. A complete list of excluded trials assessed in full-text with reasons for exclusion is given in Supplementary Table S2.

The AMSTAR evaluation of the included systematic reviews is presented in Supplementary Table S3. Concerning the rigor and transparency of the literature search and inclusion of primary trials (domain 1–4), we judged that the reviews were of sufficient quality to enable us to base our search for primary trials on their last search date.

The characteristics of the included trials are available in Supplementary Table S1. The populations included patients with adjustment disorder in 6 trials [3, 14, 15, 43, 51, 63], patients with generalized anxiety disorder in 14 trials [19, 30, 35, 38, 40,41,42, 49, 51,52,53, 61, 64, 66], patients with social anxiety disorder in 5 trials [36, 74,75,76], and patients with panic disorder in 9 trials [1, 2, 4, 16, 31, 34, 45, 56, 69].

All trials included participants of both sexes, except for the trial by Ravazzi et al., who included a population of women with breast cancer [51]. In the vast majority of trials, there was a preponderance of women and the trials involved patients with an average age between 33 and 57 years. The majority of trials included only outpatients [3, 4, 14, 16, 19, 30, 35, 38, 40, 42, 43, 45, 49, 52, 53, 56, 63, 64, 66, 69, 73, 74]. In one trial, the population consisted of both inpatients and outpatients [1], in two trials the patients were inpatients [34, 61] and in eight trials, there was no information on hospitalization status [2, 15, 31, 35, 41, 66, 75, 76].

In the vast majority of trials, there was no information on whether the symptoms of anxiety were newly onset, and in the trials that had information on duration, the patients had suffered from symptoms for at least 1 year [2, 16, 31, 34, 36, 45, 53, 56, 64, 66, 73, 74] except in the trial by Ansseau et al. [3], where the patients had experienced symptoms for an average of 2 months.

None of the trials had information on whether non-pharmacological treatment had been considered or tested.

In most trials, patients with psychotic disorders [1, 2, 16, 30, 31, 34, 36, 38, 40, 42, 45, 51,52,53, 56, 63, 64, 66, 73,74,75,76], depression [2, 15, 16, 19, 30, 34, 36, 38, 42, 43, 45, 49, 51, 53, 56, 61, 63, 64, 73, 74] and/or bipolar disorders [1, 31, 34,