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Mechanisms of Action of Antidepressants

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Summary

The need to develop new antidepressants has been motivated by the frequency and potential severity of the adverse effects of the tricyclic and monoamine oxidase inhibitor antidepressants. This search for new classes of antidepressants has led to the development of selective inhibitors of noradrenaline (norepinephrine) or serotonin (5-hydroxytryptamine; 5-HT) reuptake, reversible inhibitors of monoamine oxidase, and noradrenergic and specific serotonergic antidepressants. While such novel antidepressants have different pharmacological profiles, there is no evidence that their therapeutic efficacy is superior to that of the tricyclic antidepressants. This raises the question of whether there is a common mechanism of antidepressant effect that may be activated via different neurochemical processes. Some of the possible mechanisms whereby chronic administration of antidepressants may elicit adaptive changes in serotonergic, noradrenergic and other neurotransmitter systems are discussed against the background of the biochemical basis of depression. Finally, the need to improve the efficacy of antidepressants, possibly by utilising mechanisms other than those involving direct modulation of monoamine neurotransmitters (e.g. by changes in prostaglandins, cytokines and neuropeptides such as corticotropin-releasing factor), is discussed.

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  1. Department of Pharmacology, University College, Galway, Ireland

    B. E. Leonard

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Leonard, B.E. Mechanisms of Action of Antidepressants. CNS Drugs 4 (Suppl 1), 1–12 (1995). https://doi.org/10.2165/00023210-199500041-00003

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