Though most of the clinical trials on the antidepressant efficacy of CRF1 receptor blockers were discontinued because of adverse reactions (Holsboer and Ising 2008), considerable reductions in anxiety-related symptoms and sleep disturbances, improved mood, drive, and cognitive symptoms, and reduced suicidality were observed in patients with major depression after therapy with R121919 (a CRF1 antagonist). Here, CRHR1 is linked to major depressive disorder.