Depot neuroleptics have been widely introduced for long-term treatment of schizophrenia. The question of whether depot antidepressants should be developed for the treatment of chronic depression and for the prophylaxis of recurrent depression is addressed. This approach seems to be indicated in patients showing poor compliance to oral antidepressive medication and in patients suffering from secondary depression and who are already receiving depot antipsychotics, but it is also indicated in subgroups of patients who, for social, cultural or personality reasons, have problems with regard to a regular and long-term intake of oral medication. Before the development of depot antidepressants is initiated, the ethical issues relating to this form of medication should be discussed. Technically, the preparation of depot forms may represent a serious challenge. Depot antipsychotics are all esters of hydroxylated neuroleptics and long-chain fatty acids. Potential candidates for antidepressants are venlafaxine, flesinoxan and E-10-OH-nortriptyline. The possibility of developing forms for transdermal application is also discussed. In conclusion, clinical considerations support the idea of the usefulness of a depot preparation for antidepressants but ethical and technical aspects should not be neglected.