Targets of drug action, understanding wanted and
unwanted effects of antidepressants
background Antidepressants differ in their ability to enhance monoaminergic action and their affinity for different receptors. This results in different mechanisms of action and different profiles of side-effects.
aim To provide an updated review of the literature on mechanisms of action and on the emergence of side-effects, and to discuss the implications for the use of antidepressants in clinical practice.
method Recent scientific literature on the subject was reviewed and will be discussed.
results Despite differences in targets of drug action all antidepressants appear to modify intracellular routes of signal transduction finally leading to changes in the functioning and growth of neurons. One example is hippocampal neurogenesis. Antidepressants normalize the processing of emotional stimuli, including correction of attentional and memory bias for negative emotional stimuli. In this way antidepressants restore normal activity in a network of brain regions that is dysfunctioning in persons with a depressive disorder. In addition, at least some antidepressants appear to increase the incentive value of rewards through activation of the dopaminergic ‘reward’ system. In terms of side-effects, there exist significant differences between antidepressants. Differences in the profile of receptor affinities provide a bijblijfsessies clear basis to understand these differences in unwanted effects.
conclusion Neurotrophic changes have been shown to underlie the mechanism of action of antidepressants. This is in line with the experience that it takes a couple of weeks before therapeutic effects fully evolve. The way antidepressantaction is reached differs between antidepressants. This knowledge may be relevant for efficacy. Furthermore, knowledge about differences in the probabilities of the emergence of variousside-effects should be used to guide the choice of a particular compound, be it as first choice or as a next-step strategy. Understanding the mechanisms of action is an important tool to match the treatment with the needs and experiences of a particular individual patient.