Loading dose imipramine--new approach to pharmacotherapy of melancholic depression

This study investigated the therapeutic efficacy of loading doses of imipramine hydrochloride and compared it with that of conventional gradually escalating dose regimen of the same drug in 16 melancholic depressives (DSM III-R), done in a comparative, randomized, double-blind research design. There were four males and four females in each group who were comparable on socio-demographic and clinical variables. The study group received the bolus doses of imipramine on two consecutive days and was free of any antidepressant treatment between day 3 and day 7 of the treatment period, whereas the control group received the conventional regime of gradual escalation of imipramine dose over a period of 7 days. The results indicate that imipramine hydrochloride can relieve depression almost completely within 72 h, if given in high bolus doses, thus challenging the theory of lag period for antidepressant action as an inherent property of this drug. The study shows that the pulse loading dose was superior to a conventional dose regime with regard to both antidepressant efficacy and rapidity of onset of action. The various mechanisms possibly involved in such a dramatic improvement and its implications have been discussed.