Comparison of the Effect of Imipramine and Desipramine on Some Symptoms of Depressive Illness

The possibility that desipramine might prove to be a rapidly acting antidepressant was first raised by laboratory studies. In 1959 desipramine was isolated as a metabolite of imipramine (Hermann et al., 1959; Hermann and Pulver, 1960), and a series of papers then followed (Brodie et al., 1961; Gillette et al., 1961; Sulser et al., 1962) in which it was shown that reserpine-induced inactivity in the rat can be more rapidly reversed by desipramine than by imipramine. This was referred to (Gillette et al., 1961) as an experimental demonstration of the relative rapidity of the “antidepressant” action of the two drugs. Other experimental reports should however warn against incautious interpretation of laboratory findings. Garattini et al. (1962) showed that desipramine is not responsible for all the actions of imipramine: in mice, leptazol convulsions are inhibited by the latter but not by the former drug. Dingell et al. (1964) were able to show considerable species differences in the rate at which imipramine is converted to desipramine and in the rate at which desipramine is then destroyed. Their paper also emphasizes the paucity of information on the metabolism of imipramine in human subjects.