Antidepressant medications have an onset of action of several weeks and have moderate efficacy. Their mode of administration is oral (p.o.). Some clinicians wondered whether intravenous (i.v.) administration would speed onset of action and increase efficacy. In this article we review controlled studies on i.v. administration of antidepressants. These include clomipramine, citalopram, and other antidepressants. Overall these studies do not support increased efficacy of i.v. over p.o.administration but there are suggestions of a faster onset of action. In one study i.v. citalopram showed superior response rates over p.o. citalopram (79% vs. 63%) in severely depressed patients at 8 weeks.