Novel and emerging treatments for major depression

Mush Room for Improving Therapeutic Approaches in Psychiatry

“…This has occurred alongside a broader resurgence of research into therapeutic applications of psychedelic agents. 8,9 As in every other area of drug development, the involvement of clinical pharmacology will be a key determinant of success and Clinical Pharmacology & Therapeutics (CPT) expects to see an increase in submissions and publications in this area. Recent examples are the reports on pharmacokinetics-pharmacodynamics (PKPD) of lysergic acid diethylamide (LSD) microdosing 10 and PKPD interactions between psilocybin and escitalopram.…”

“…The clinical pharmacology of psilocybin was already reviewed in this journal six decades ago ago, 6 but interest from the scientific and clinical community seems to have gathered serious momentum only in the last 5 years ( Figure ). This has occurred alongside a broader resurgence of research into therapeutic applications of psychedelic agents 8,9 . As in every other area of drug development, the involvement of clinical pharmacology will be a key determinant of success and Clinical Pharmacology & Therapeutics ( CPT ) expects to see an increase in submissions and publications in this area.…”

Importance of achieving rapid treatment response in major depressive disorder

“…Psilocybin, a 5-hydroxy-tryptamine type 2A receptor agonist, is a psychedelic compound that can improve depressive symptoms in conjunction with psychotherapy, with studies demonstrating effects 1 week postdose that were sustained through 8 weeks without maintenance dosing. 24,34 However, some patients treated with psilocybin have experienced emotional effects, including anxiousness, fear, and other emotional distress during treatment sessions, and use of psilocybin is limited by the need to receive treatment in a clinical setting and remain under supervision for several hours. 24,34,35 Esmethadone, a novel NMDA receptor antagonist, can provide improvements in as little as 4 days of treatment in patients for whom up to 3 ADTs failed, but its long-term efficacy is unknown.…”

“…24,34 However, some patients treated with psilocybin have experienced emotional effects, including anxiousness, fear, and other emotional distress during treatment sessions, and use of psilocybin is limited by the need to receive treatment in a clinical setting and remain under supervision for several hours. 24,34,35 Esmethadone, a novel NMDA receptor antagonist, can provide improvements in as little as 4 days of treatment in patients for whom up to 3 ADTs failed, but its long-term efficacy is unknown. 24 Modulation of GABAergic signaling is an evolving approach to treat MDD among investigational therapies (Table 1).…”

“…https://doi.org/10.1017/S1092852923002213 Published online by Cambridge University Press Accepted Manuscript: Authors' Copy Ketamine, esketamine, and dextromethorphan-bupropion are thought to act as N-methyl-Daspartate (NMDA) receptor antagonists and elicit antidepressant effects through modulation of glutamate signaling (Table1). These agents demonstrate rapid effects in as little as an hour, with improvements in depressive symptoms sustained up to 6 weeks [23][24]24.…”