New and emerging treatments for major depressive disorder.

Major depressive disorder (MDD) affects many people, but its underlying causes remain unclear. Treatment resistance points to the disorder's heterogeneity and the need for therapies beyond monoamine neurotransmission. This review examines emerging targets for MDD, including psychedelics, antibiotics, opioid modulators, neuropeptides, and onabotulinumtoxin, as well as neuromodulatory treatments like light-based therapies, magnetic stimulation, and electrical stimulation. Most interventions were tested as add-ons to antidepressants. Research on psychedelics is most advanced, with trials suggesting rapid antidepressant and anti-suicidal effects. The review considers trial findings, tolerability, study design limitations, and research quality. Currently, forming recommendations is challenging, but future research may allow more robust guidance.

Study at a glance

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.