Incidence of adverse events and comparative tolerability of selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for the treatment of anxiety, obsessive-compulsive, and stress disorders: a systematic review and network meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and network meta-analysis of randomized controlled trials
PubMed 37278215 · doi:10.1017/S0033291723001630
What was done
Authors conducted a systematic review and network meta-analysis searching MEDLINE, PsycINFO, Embase, Cochrane, regulatory websites, and international registers through September 9, 2022. They evaluated randomized controlled trials assessing SSRIs or SNRIs in children and adults with anxiety, obsessive-compulsive, and stress-related disorders. They calculated the proportion of participants experiencing at least one adverse event and incidence rates across 17 specific adverse events using random-effects and three-level models.
What was found
Analyzing 799 outcome measures from 80 studies (n = 21,338), participants in medication groups experienced higher adverse event rates (80.22%, 95% CI 76.13–83.76) compared to placebo groups (71.21%, 95% CI 67.00–75.09). Nausea was the most common adverse event (25.71%, 95% CI 23.96–27.54), while weight change was the least common (3.56%, 95% CI 1.68–7.37). Most medications had higher adverse event rates than placebo, except sertraline and fluoxetine. Significant differences between medications emerged for overall tolerability and for autonomic, gastrointestinal, and sleep-related symptoms.
Why it matters
Because SSRIs and SNRIs show comparable efficacy across anxiety and stress disorders, tolerability is key for clinical decision-making. Comparative adverse event profiling helps clinicians tailor drug choices to minimize discontinuation and improve adherence.
Limits
The abstract pools pediatric and adult populations without providing age-stratified metrics. Specific odds ratios, individual drug-to-drug comparison values, and trial durations or dosing schedules are not reported in the abstract.
Cited by
- supports SSRIs have a side effect rate of approximately 50% and a withdrawal/discontinuation effect rate of approximately 50%.