Recent Advances in the Treatment of Treatment-Resistant Depression: A Narrative Review of Literature Published from 2018 to 2023
John L. Havlik, Syed Wahid, Kayla M Teopiz, Roger S McIntyre, John H. Krystal, Taeho Greg Rhee
Current Psychiatry Reports April 1, 2024 DOI: 10.1007/s11920-024-01494-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Esketamine Ketamine Depression |
| Keywords | Treatment-resistant depression trd Electroconvulsive therapy ect Pharmacotherapy |
| Citations | 30 |
| Key findings | Interventional approaches such as electroconvulsive therapy, ketamine/esketamine, and transcranial magnetic stimulation are supported by recent evidence for treatment-resistant depression. |
Abstract
Purpose of Review We review recent advances in the treatment of treatment-resistant depression (TRD), a disorder with very limited treatment options until recently. We examine advances in psychotherapeutic, psychopharmacologic, and interventional psychiatry approaches to treatment of TRD. We also highlight various definitions of TRD in recent scientific literature. Recent Findings Recent evidence suggests some forms of psychotherapy can be effective as adjunctive treatments for TRD, but not as monotherapies alone. Little recent evidence supports the use of adjunctive non-antidepressant pharmacotherapies such as buprenorphine and antipsychotics for the treatment of TRD; side effects and increased medication discontinuation rates may outweigh the benefits of these adjunctive pharmacotherapies. Finally, a wealth of recent evidence supports the use of interventional approaches such as electroconvulsive therapy, ketamine/esketamine, and transcranial magnetic stimulation for TRD. Summary Recent advances in our understanding of how to treat TRD have largely expanded our knowledge of best practices in, and efficacy of, interventional psychiatric approaches. Recent research has used a variety of TRD definitions for study inclusion criteria; research on TRD should adhere to inclusion criteria based on internationally defined guidelines for more meaningfully generalizable results.
Comparable studies
Other narrative reviews on esketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 | |
| Long-term safety of ketamine and esketamine in treatment of depression | 2022 | Review | |
| Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. | 2024 | Review | |
| Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. Patients with depression | 2024 | Narrative review | |
| The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease | 2022 | Review |
Citations in the library
Cited by 12
- Hepatic adverse events associated with ketamine and esketamine: A population-based disproportionality analysis. Journal of Affective Disorders April 1, 2025
- Esketamine/Ketamine: Dual‐Action Mechanisms and Clinical Prospects beyond Anesthesia in Psychiatry, Immunology, and Oncology Advanced Science December 14, 2025
- Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis. Pharmaceuticals May 9, 2025
- Auto-Induction in Oral Esketamine Treatment for Treatment-Resistant Depression: An Exploratory Study. Pharmaceuticals April 25, 2025
- Ketamine's Influence on Magnetoencephalography Patterns During a Working Memory Task in Treatment-Resistant Depression: An Exploratory Study. Bipolar Disorders April 2, 2025
and 7 more in the library
Cites 16
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression The Journal of Clinical Psychiatry April 20, 2020
- Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. New England Journal of Medicine May 24, 2023
- Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study. Journal of Affective Disorders November 14, 2019
and 11 more in the library