Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects

A method of treating a human subject unresponsive to antidepressants with enhanced plasma levels of a dextromethorphan, wherein the human subject is an extensive metabolizer of the dextromethorphan and has failed or has had an inadequate response to treatment with at least one antidepressant, comprising co-administering to the human subject a daily dose of a combination, wherein the combination comprises:

• 1) a bupropion, and
• 2) the dextromethorphan,
• wherein the combination is administered once or twice a day for at least eight consecutive days, and
• wherein co-administration of the bupropion, and the dextromethorphan results in a first Cmin of the dextromethorphan that is at least about 20 ng/mL, on the eighth day of consecutive administration, and the first Cmin of the dextromethorphan is at least about 20 times a second Cmin of the dextromethorphan that would result from administering the daily dose of the dextromethorphan without the bupropion to the human subject for eight consecutive days.