Selective serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI) lead prescription statistics worldwide and are listed in guidelines as first-line antidepressants. While they do not show higher efficacy than the traditional antidepressant generations such as tricyclic antidepressants (TCA), their higher selectivity conveys better tolerability and low toxicity in overdose. Despite these advances, all antidepressants to date have in common that there is usually a latency of several weeks before the desired onset of action, and the proportion of patients with inadequate treatment success remains relatively high. This might be due to the fact that the available antidepressants probably exert their effects via a common mechanism, the modulation of monoaminergic neurotransmitter systems (serotonin, norepinephrine, and dopamine). The discovery of new pharmacological mechanisms of action of antidepressant therapies received a noticeable boost several years ago with the exploration of the potential role of the glutamatergic neurotransmitter system in the pathogenesis of depression. Particularly, esketamine, a new and rapidly effective antidepressant, is now available for clinical use (FDA/EMA approval 2019). However, it remains to be seen how esketamine and similar substances with an effect on NMDA receptors will prove themselves in broad clinical use in the coming years. Furthermore, psychedelics such as the serotonin receptor agonist psilocybin, ayahuasca, and lysergic acid diethylamide (LSD) are being investigated for their potential as fast-acting antidepressants. This session aims at providing an overview of the current state of clinical studies on fast acting antidepressants, their neurobiological mechanisms as well as potential pitfalls.
This session was recorded on 9 October 2023 at the 36th ECNP Congress in Barcelona.
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