Management of Treatment-Resistant Depression: Challenges and Strategies
Daphne Voineskos, Zafiris J Daskalakis, Daniel M. Blumberger
Neuropsychiatric Disease and Treatment 2020 DOI: 10.2147/ndt.s198774 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | lithium triiodothyronine second-generation antipsychotics electroconvulsive therapy repetitive transcranial magnetic stimulation magnetic seizure therapy deep brain stimulation ketamine psilocybin anti-inflammatories |
| Topics | Anxiety Depression |
| Keywords | Antidepressant Deep brain stimulation Transcranial magnetic stimulation Vagus nerve stimulation Modalities Depression economics Bipolar disorder Psychotherapist Intensive care medicine Lithium medication Schizophrenia object-oriented programming Mood Electroconvulsive therapy studies |
| Citations | 430 |
| Key findings | Further large-scale work is necessary to understand appropriate treatment pathways for treatment-resistant depression and to prescribe effective therapeutic options. |
Abstract
Treatment-resistant depression (TRD) is a subset of Major Depressive Disorder which does not respond to traditional and first-line therapeutic options. There are several definitions and staging models of TRD and a consensus for each has not yet been established. However, in common for each model is the inadequate response to at least 2 trials of antidepressant pharmacotherapy. In this review, a comprehensive analysis of existing literature regarding the challenges and management of TRD has been compiled. A PubMed search was performed to assemble meta-analyses, trials and reviews on the topic of TRD. First, we address the confounds in the definitions and staging models of TRD, and subsequently the difficulties inherent in assessing the illness. Pharmacological augmentation strategies including lithium, triiodothyronine and second-generation antipsychotics are reviewed, as is switching of antidepressant class. Somatic therapies, including several modalities of brain stimulation (electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy and deep brain stimulation) are detailed, psychotherapeutic strategies and subsequently novel therapeutics including ketamine, psilocybin, anti-inflammatories and new directions are reviewed in this manuscript. Our review of the evidence suggests that further large-scale work is necessary to understand the appropriate treatment pathways for TRD and to prescribe effective therapeutic options for patients suffering from TRD.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cited by 79
- Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic Review Frontiers in Psychiatry July 12, 2022
- Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life Journal of Affective Disorders February 3, 2023
- Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. Journal of Affective Disorders February 1, 2023
- Novel drug developmental strategies for treatment‐resistant depression British Journal of Pharmacology November 25, 2021
- Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. American Journal of Psychiatry March 1, 2025
and 74 more in the library
Cites 9
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial The International Journal of Neuropsychopharmacology March 17, 2009
and 4 more in the library