MODERN STRATEGIES FOR THE TREATMENT OF TREATMENT-RESISTANT DEPRESSION – A LITERATURE REVIEW
Ignacy Rożek, Wojciech Gąska, Izabela Lekan, Joanna Mazurek, Agnieszka Brzezińska, Weronika Tuszyńska, Alicja Sodolska, Michał Lenart, Barbara Madoń, Barbara Teresińska
International Journal of Innovative Technologies in Social Science September 30, 2025 DOI: 10.31435/ijitss.3(47).2025.3822 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression |
| Keywords | Depression economics Repurposing Antidepressant Neuromodulation Variety cybernetics Action physics Medline Intensive care medicine Psychotherapist Clinical practice Clinical trial |
| Key findings | Ketamine, esketamine, and psilocybin are promising options for treatment-resistant depression, and repurposing agents like lurasidone, pioglitazone, and minocycline may offer new mechanisms of action. |
Abstract
Treatment-resistant depression (TRD) remains a major therapeutic challenge in psychiatry, affecting a substantial proportion of individuals diagnosed with major depressive disorder and contributing significantly to the overall burden of mental illness. Despite decades of research and the availability of numerous antidepressant agents, many patients fail to achieve full remission, which underscores the urgent need for more effective interventions. This review provides a comprehensive and up-to-date analysis of both established and novel strategies for the management of TRD, encompassing pharmacological augmentation approaches, a variety of neuromodulation techniques, the clinical application of psychedelic- assisted therapies, and the development of innovative compounds currently under investigation. Particular emphasis is placed on the therapeutic potential and clinical outcomes associated with ketamine, esketamine, and psilocybin, which have emerged as promising options for patients who do not respond to conventional treatments. In addition, the review explores future directions in TRD management, including the repurposing of agents such as lurasidone, pioglitazone, and minocycline, which may offer new mechanisms of action and improved tolerability. Finally, the discussion highlights the importance of adopting a personalized, evidence-based, and multidimensional treatment approach, with the goal of improving both short-term response rates and long-term functional recovery in individuals 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
Cites 14
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Ketamine for the treatment of major depression: a systematic review and meta-analysis EClinicalMedicine August 1, 2023
and 9 more in the library