Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder
This review (2015) discusses research developments regarding therapeutic compounds that exert their antidepressant efficacy via the glutamatergic, cholinergic, and opioid systems. The authors encourage innovative research strategies for improving the efficacy of treatments such as ketamine, whose effects are rapid but not long-lasting.
Authors
- Daniel Ionescu
- George Papakostas
Published
Abstract
Review: Depression is a devastating disorder that places a significant burden on both the individual and society. As such, the discovery of novel therapeutics and innovative treatments-especially for treatment-resistant depression (TRD)-are essential. Research into antidepressant therapies for TRD has evolved from explorations of antidepressants with primary mechanisms of action on the monoaminergic neurotransmitter system to augmentation agents with primary mechanisms both within and outside of the serotonin/norepinephrine system. Now the field of antidepressant research has changed trajectories yet again; this time, compounds with primary mechanisms of action on the glutamatergic, cholinergic and opioid systems are in the forefront of antidepressant exploration. In this review, we will discuss the most recent research surrounding these novel compounds. In addition, we will discuss novel device-based therapeutics, with a particular focus on transcranial magnetic stimulation. In many cases of antidepressant drug discovery, the role of serendipity coupled with meticulous clinical observation in drug development in medicine was crucial. Moving forward, we must look toward the combination of innovation plus improvements on the remarkable discoveries thus far to advance the field of antidepressant research.
Research Summary of 'Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder'
Introduction
Depression is described as a highly burdensome, pervasive disorder for which a large proportion of patients do not achieve adequate benefit from standard treatments. The paper focuses on treatment-resistant depression (TRD), operationalised in the text as failure to achieve response to one or more adequate antidepressant trials, and highlights that, after decades of monoaminergic drug development, many patients remain symptomatic and therefore require new therapeutic strategies. Papakostas outlines a shift in research trajectories away from sole reliance on monoaminergic mechanisms towards agents acting on glutamatergic, cholinergic and opioid systems, as well as device-based and procedural therapies. The review updates an earlier overview of TRD from roughly five years prior, organising the discussion by drug class and addressing both pharmacological and device interventions with an emphasis on novel and rapidly acting approaches.
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Study Details
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- APA Citation
Papakostas, G. I., & Ionescu, D. F. (2015). Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder. Molecular Psychiatry, 20(10), 1142-1150. https://doi.org/10.1038/mp.2015.92
References (5)
Papers cited by this study that are also in Blossom
Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Sos, P., Klirova, M., Novák, T. et al. · Neuropsychiatric Disease And Treatment (2013)
Murrough, J. W., Iosifescu, D. V., Chang, L. C. et al. · American Journal of Psychiatry (2013)
Ionescu, D. F., Luckenbaugh, D. A., Niciu, M. J. et al. · Bipolar Disorders (2014)
Murrough, J. W., Wan, L., Levitch, C. F. et al. · Journal of Clinical Psychiatry (2015)
Cited By (3)
Papers in Blossom that reference this study
Ellis, S., Bostian, C., Donnelly, A. et al. · Journal of Affective Disorders (2025)
Murrough, J. W., Abdallah, C. G., Mathew, S. J. · Nature Reviews Drug Discovery (2021)
Schwartz, J., Murrough, J. W., Iosifescu, D. V. · Evidence-Based Mental Health (2016)
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