Early onset of therapeutic action in depression and greater efficacy of antidepressant treatments: are they related?

Until recently, several weeks of treatment were required to obtain a clinically significant antidepressant response using pharmacotherapy. Now treatment strategies have been developed that appear to produce an early onset of action in major depression. In treatment-resistant depression, there are several agents that can be used to potentiate the therapeutic effect of the initial antidepressant drug. The question of whether such a rapid onset is related to greater efficacy of antidepressant treatments was examined on the basis of the putative mechanisms of action of these treatments, and on the clinical evidence available so far. Some approaches appear to have both a more rapid onset of action and greater efficacy, such as electroconvulsive shock treatment, venlafaxine and pindolol addition, whereas the addition of lithium does not produce a more rapid onset of action despite being effective in treatment-resistant depression. In contrast, amineptine exerts an early psychostimulant effect but is apparently as effective as other antidepressant drugs. We conclude that a treatment strategy producing a rapid onset often, but not invariably, has greater efficacy than a treatment producing a slower onset. These preclinical and clinical observations may help to devise rapid treatments for major depression that will be effective in a greater proportion of patients than at present.