Amitriptyline, a tricyclic antidepressant, and fluoxetine, a selective serotonin reuptake inhibitor, have been shown to inhibit the activity of ASM, to reduce ceramide concentrations and ASM protein levels in cultured neurons and in the hippocampus of wild-type (WT) and t-ASM mice and to normalize the depressive- and anxiogenic-like phenotype of t-ASM mice when administered at doses that achieve therapeutic plasma concentrations recommended for patients with MDD [9]. The gene discussed is SMPD1; the disease is major depressive disorder.