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New and emerging treatments for major depressive disorder.

Cecilia Njenga, Parashar Pravin Ramanuj, Frederico Jose Coelho De Magalhães, Harold Alan Pincus

BMJ (Clinical research ed.) July 8, 2024 DOI: 10.1136/bmj-2022-073823

Summary

Psychedelics show promise in treating major depressive disorder (MDD), with trials indicating rapid antidepressant and anti-suicidal effects. A review of various interventions highlights the need for diverse treatment approaches beyond traditional methods, noting that nearly all were tested alongside standard antidepressants. With a focus on psychedelics, the findings underscore challenges in study design and quality, yet they signal a growing interest in innovative treatments like antibiotics, opioid modulators, and neuromodulatory therapies. Future research may pave the way for more definitive recommendations.

Abstract

Major depressive disorder (MDD) affects a substantial portion of the population; however, much is still unknown about the pathophysiology of this disorder. Treatment resistance highlights the heterogeneous nature of MDD and the need for treatments to target more than monoamine neurotransmission. This review summarizes research into the new and emerging targets of MDD. These include drugs such as psychedelics, antibiotics, opioid modulators, neuropeptides, and onabotulinumtoxin. Neuromodulatory treatments such as light based therapies and neuromodulation involving either magnetic or electrical stimulation are also discussed. Almost all interventions, pharmacological and neuromodulation, were trialed as adjunctive treatments to an antidepressant. Most research has been conducted on psychedelics, with trials suggesting rapid antidepressant and anti-suicidal effects. Trial findings, tolerability, study design limitations and quality of research have been considered throughout this review. There remains challenges in forming recommendations with the current research at present. With there being considerable interest into the research of new and emerging treatments-in particular, psychedelics-there may be scope in the future to form more robust recommendations.

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