SLC6A4 and major depressive disorder: To allow SERT inhibitors to achieve their therapeutic effects in MDD patients, it is necessary to not only elevate the extracellular levels of serotonin but also sustain the increase over the course of the day; it has been shown that tryptophan depletion causes a relapse in ~50% of remitted MDD patients within hours—an effect that may be exacerbated in females and chronically ill patients treated with SSRIs [21].