Rapid acting antidepressants - current status and new developments. Part 2: Psychedelics, neurosteroids and further compounds Schnell wirkende Antidepressiva: aktueller Stand und neue Entwicklungen Teil 2: Psychedelika, Neurosteroide und weitere Substanzen

Currently approved conventional antidepressants exhibit a significantly delayed onset of action, taking several weeks. As described in our previous review article in this series, this has led to increased research into rapid-acting antidepressants (RAADs). With the approval of intranasal esketamine in 2019, a substance from a new class of drugs (NMDA receptor antagonism) was approved as the first RAAD. In the previous article, we focused on potential novel RAADs targeting the glutamatergic system; here, we aim to evaluate other drugs with different pharmacological targets regarding their suitability as RAADs based on clinical studies. These classes of substances mainly include psychedelics (such as psilocybin, lysergic acid diethylamide [LSD], Ayahuasca/dimethyltryptamine [DMT]), 3,4-methylenedioxy-N-methylamphetamine [MDMA], GABAergic substances (i.e., positive allosteric modulators [PAM] of GABA-A receptors [GABA-PAM; PRAX-114, propofol, zuranolone]), opioidergic substances (my-opioid receptor partial agonists [mOR-pA; buprenorphine], kappa-opioid receptor antagonists [kOR-A; aticaprant, navacaprant]), and scopolamine.