Gosmann NP, de Abreu Costa M, de Barros Jaeger M, et al. - Patients frequently have co-occurrence of anxiety, obsessive-compulsive, and stress-related disorders, and presence of symptoms of several domains. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are used in treating these patients. Researchers herein sought for data on the comparative efficacy and acceptability of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis. Analysis of 469 outcome measures from 135 studies (n = 30,245) was performed. SSRIs and SNRIs were described as effective for multiple symptom domains, and in patients from all included diagnostic categories. Medications showed minimal differences concerning efficacy and acceptability. This 3-level network meta-analysis contributes strong evidence to the ongoing discussion concerning the true benefit of antidepressants, with a significantly larger quantity of data and higher statistical power than prior studies. The 3-level approach allowed precise assessment of the efficacy of these medications on internalizing psychopathology, averting potential biases linked with the exclusion of information due to distinct assessment instruments, and to determine the multilevel structure of transdiagnostic efficacy.