Mechanisms underlying the speed of onset of antidepressant response

Abstract

Depression is an incapacitating disorder with serious health and economic consequences. It has an estimated cost of more than $ 43 billion annually in the US (Greenberg et al., 1993) and by the year 2020 it will be the second leading cause of disease burden behind ischaemic heart disease (The Global Burden of Disease and Injury Series, 1996). Despite extensive research, very little is known about the aetiology of depressive illness or the mechanism of action of drugs used in its treatment. Although effective, there are a number of disadvantages to the use of antidepressants. Firstly, there is a delay of 3-4 weeks before any therapeutic effects of these drugs are seen. This is a serious problem since there is an increased incidence of suicide in depressed patients and a lifetime incidence of suicide of 15% has been reported from follow-up studies (Smith and Weissman, 1992; Norman and Leonard, 1994). Secondly, antidepressants, particularly the early generation, are often associated with unpleasant side effects such as dry mouth, blurred vision, urinary hesitancy, dizziness on standing, which reduce patient compliance. Improvements have been made with newer antidepressants which are based on the same mechanism of action. Venlafaxine blocks the reuptake of noradrenaline and serotonin but lacks the alpha 1, cholinergic and histaminergic receptor blocking properties of the TCA’s, while nefazodone, the 5-HT₂ receptor antagonist, has less side-effects than the SSRI’s.