Major Depressive Disorder (MDD)Depressive DisordersKetamine

New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity

This review (2017) examines treatment strategies for depression based on neuroplasticity induction via non-invasive brain stimulation and NMDA receptor and glutamatergic modulation via ketamine. The authors raise concerns over the long-term antidepressive efficacy and safety of ketamine and highlight other MDA receptor and glutamate modulators, such as sarcosine, which show antidepressive effects in small-scale studies.

Authors

  • Huang, Y. J.
  • Lane, H. Y.
  • Lin, C. H.

Published

Neural Plasticity
meta Study

Abstract

Review: Major depressive disorder is a severe and complex mental disorder. Impaired neurotransmission and disrupted signalling pathways may influence neuroplasticity, which is involved in the brain dysfunction in depression. Traditional neurobiological theories of depression, such as monoamine hypothesis, cannot fully explain the whole picture of depressive disorders. In this review, we discussed new treatment directions of depression, including modulation of glutamatergic system and noninvasive brain stimulation. Dysfunction of glutamatergic neurotransmission plays an important role in the pathophysiology of depression. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and lasting antidepressive effects in previous studies. In addition to ketamine, other glutamatergic modulators, such as sarcosine, also show potential antidepressant effect in animal models or clinical trials. Noninvasive brain stimulation is another new treatment strategy beyond pharmacotherapy. Growing evidence has demonstrated that superficial brain stimulations, such as transcranial magnetic stimulation, transcranial direct current stimulation, cranial electrotherapy stimulation, and magnetic seizure therapy, can improve depressive symptoms. The antidepressive effect of these brain stimulations may be through modulating neuroplasticity. In conclusion, drugs that modulate neurotransmission via NMDA receptor and noninvasive brain stimulation may provide new directions of treatment for depression. Furthermore, exploring the underlying mechanisms will help in developing novel therapies for depression in the future.

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Research Summary of 'New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity'

Introduction

Major depressive disorder (MDD) is a common, disabling condition with substantial personal and societal burden. Huang and colleagues note that existing antidepressant treatments are limited by slow onset, incomplete efficacy and adverse effects, with real-world remission rates often well below ideal: first-line remission around 30% and cumulative remission after multiple treatment steps only around 67% in one cited programme. The authors highlight that monoamine-focused theories do not fully explain depression; disrupted intracellular signalling and impaired neuroplasticity — including reduced neurotrophic factor expression and altered functional connectivity — are increasingly implicated in the pathophysiology and may underlie residual symptoms despite treatment. This review sets out to examine emerging treatment strategies for depression that target mechanisms related to neuroplasticity. Specifically, Huang and colleagues focus on pharmacological modulation of the glutamatergic system (particularly interventions affecting NMDA receptors and downstream signalling such as mTOR and BDNF) and on noninvasive brain stimulation techniques, surveying preclinical and clinical evidence and discussing mechanistic rationales for these approaches.

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Study Details

References (6)

Papers cited by this study that are also in Blossom

Antidepressant effects of ketamine in depressed patients

Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)

Ketamine as a promising prototype for a new generation of rapid-acting antidepressants

Abdallah, C. G., Averill, L. A., Krystal, J. H. · Annals of the New York Academy of Sciences (2015)

Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

Murrough, J. W., Perez, A. M., Pillemer, S. et al. · Biological Psychiatry (2012)

R (−)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine

Zhang, J., Hashimoto, K., Li, S. · Pharmacology Biochemistry and Behavior (2014)

R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects

Yang, C., Shirayama, Y., Zhang, J-C. et al. · Translational Psychiatry (2020)

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