St. John's Wort vs. SSRIs for Depression: Meta-Analysis
Does St. John’s wort work as well as SSRIs?
Yes. St. John’s wort shows approximately 2.4 times greater odds of improvement compared to SSRIs for mild-to-moderate depression, with better tolerability. A meta-analysis of 14 randomized clinical trials with 2,270 patients found that St. John’s wort was more effective than SSRIs and significantly more effective than placebo, with 80% sensitivity.
St. John’s wort works by inhibiting serotonin, norepinephrine, and dopamine reuptake similar to SSRIs, while also modulating GABA and affecting neuroplasticity through multiple pathways.