Selective Serotonin Reuptake Inhibitors, And Serotonin And Norepinephrine Reuptake Inhibitors For Anxiety, Obsessive-Compulsive, And Stress Disorders: A 3-Level Network Meta-Analysis

Author summaryWhy was this study done?Studies assessing comorbidity in patients with anxiety, obsessive-compulsive, and stress-related disorders report rates above 50%, and patients often present symptoms of multiple symptom domains.The efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) on multiple mental health domains has not yet been studied by network meta-analysis in this field, to the best of our knowledge.Meta-analyses often restrain the statistical analysis to the most commonly used assessment instruments.What did the researchers do and find?We conducted a systematic review and 3-level network meta-analysis of 469 outcome measures, including all available measures of outcomes related to anxiety, obsessive-compulsive, and stress-related disorders.SSRIs and SNRIs presented small to moderate effect sizes for global improvement of mental health in participants from all diagnostic categories.We also found small to moderate effect sizes in our sensitivity analysis restricted to the most used assessment instruments; however, this restriction led to the exclusion of 72.71% of all outcome measures.What do these findings mean?Our results support previous findings related to the efficacy of SSRIs and SNRIs indicating that these medications are effective in multiple health domains.This study improved the evidence of the benefit of SSRIs and SNRIs for anxiety disorders. These results should guide psychiatrists, patients, clinicians, and policy makers on better evidence-based decisions for the initial treatment of these disorders.BackgroundAnxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often present symptoms of several domains. Treatment involves the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), but data on comparative efficacy and acceptability are lacking. We aimed to compare the efficacy of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis.Methods and findingsWe searched for published and unpublished randomized controlled trials that aimed to assess the efficacy of SSRIs or SNRIs in participants (adults and children) with diagnosis of any anxiety, obsessive-compulsive, or stress-related disorder in MEDLINE, PsycINFO, Embase, and Cochrane Library from inception to 23 April 2015, with an update on 11 November 2020. We supplemented electronic database searches with manual searches for published and unpublished randomized controlled trials registered in publicly accessible clinical trial registries and pharmaceutical companies' databases. No restriction was made regarding comorbidities with any other mental disorder, participants' age and sex, blinding of participants and researchers, date of publication, or study language. The primary outcome was the aggregate measure of internalizing symptoms of these disorders. Secondary outcomes included specific symptom domains and treatment discontinuation rate. We estimated standardized mean differences (SMDs) with 3-level network meta-analysis with random slopes by study for medication and assessment instrument. Risk of bias appraisal was performed using the Cochrane Collaboration's risk of bias tool. This study was registered in PROSPERO (CRD42017069090). We analyzed 469 outcome measures from 135 studies (n = 30,245). Medication (SSRI or SNRI) was more effective than placebo for the aggregate measure of internalizing symptoms (SMD -0.56, 95% CI -0.62 to -0.51, p < 0.001), for all symptom domains, and in patients from all diagnostic categories. We also found significant results when restricting to the most used assessment instrument for each diagnosis; nevertheless, this restriction led to exclusion of 72.71% of outcome measures. Pairwise comparisons revealed only small differences between medications in efficacy and acceptability. Limitations include the moderate heterogeneity found in most outcomes and the moderate risk of bias identified in most of the trials.ConclusionsIn this study, we observed that SSRIs and SNRIs were effective for multiple symptom domains, and in patients from all included diagnostic categories. We found minimal differences between medications concerning efficacy and acceptability. This 3-level network meta-analysis contributes robust evidence to the ongoing discussion about the true benefit of antidepressants, with a significantly larger quantity of data and higher statistical power than previous studies. The 3-level approach allowed us to properly assess the efficacy of these medications on internalizing psychopathology, avoiding potential biases related to the exclusion of information due to distinct assessment instruments, and to explore the multilevel structure of transdiagnostic efficacy.