GDNF and major depressive disorder: In addition to the above-known pharmacological mechanisms, some recent studies have reported that amitriptyline can induce the activation of fibroblast growth factor receptor (FGFR), leading to the production of GDNF.354 In addition, amitriptyline can increase the expression of Cx43 to promote gap junction intercellular communication (GJIC) between astrocytes, thereby relieving depressive symptoms.355 This suggests that TCAs may also ameliorate severe depression through additional mechanisms involving astrocytes that are independent of the monoamine system to some extent.