Provided is a method for treating depression with an open-channel antagonists of the NMDA (N-methyl-D-aspartate) receptor complex. The open-channel antagonists include memantine (a 1-amino-3,5-dimethyl-adamantane hydrochloride), felbamate, acamprosate, and MRZ 2/579 (1-amino-1,3,3,5,5-pentamethyl-cyclohexane hydrochloride). The method includes oral, controlled or sustained release, intravenous, rectal, transcutaneous or other preparations such as lipid emulsion or crystal technology administration of the open-channel antagonist.