L-Theanine Adjunct to Sertraline for Major Depression: RCT
Can L-Theanine Boost Sertraline’s Effectiveness for Depression?
Yes. L-theanine significantly enhances sertraline’s effectiveness for major depression, providing superior therapeutic benefits compared to sertraline alone with excellent tolerability. A randomized, double-blind, placebo-controlled clinical trial published in the Journal of Affective Disorders demonstrates that adding this natural amino acid to sertraline treatment creates a multi-target approach that addresses depression’s complex neurobiology.
L-theanine works by modulating GABA, serotonin, and dopamine levels through different pathways than sertraline, plus it has glutamatergic and neuroimmune effects that complement sertraline’s serotonin reuptake inhibition, providing enhanced therapeutic effects through complementary mechanisms rather than single-pathway intervention.

