In our study, we found that the combination therapy of REMSD and fluoxetine reversed the effects of depression on aggravating damage and promoting apoptosis in the hippocampus, upregulating the expressions of Bax, P38 MAPK, cFos, and ADAR2 expressions, and downregulating those of Bcl-2 and PI3K. This evidence concerns the gene BCL2 and major depressive disorder.