Major Depressive Disorder as a Condition Negatively Impacting Both Mental and Physical Functioning. What to Do When There Is Treatment Resistance?
DOI:
https://doi.org/10.12775/QS.2024.35.57665Keywords
depression, treatment-resisant depression, major depressive disorder, mood disorder, antidepressant, augmentation, electroconvulsive stimulation, novel therapiesAbstract
The objective of this article is to assess the efficacy and safety of diverse therapeutic strategies for treatment-resistant depression (TRD), encompassing both pharmacological and non-pharmacological interventions. Additionally, the review identifies potential avenues for future research within this domain.
The article compares the results of selected studies. We conducted a literature search in November of 2024, using PubMed. Six studies were identified, chosen, and appraised. Among these studies, three are systematic reviews and three are narrative literature reviews.
If it comes to treatment efficacy studies have demonstrated the effectiveness of several strategies. Ketamine and esketamine have shown rapid and substantial efficacy in mitigating the symptoms of TRD. Augmentation with aripiprazole and quetiapine has also been found to enhance the response to antidepressant treatment. The combination of olanzapine and fluoxetine is effective for treating TRD, however, it may be associated with metabolic side effects. Augmentation with lithium, triiodothyronine (T3), and lamotrigine shows promising results, though further research is required to fully evaluate their efficacy and safety in TRD management.
The management of TRD is associated with several challenges. These include the absence of a standardized definition and grading system, which impedes the comparison of research outcomes. The multifactorial nature of TRD further complicates the development of a universal treatment strategy. Summarizing, there are several treatment strategies available for TRD, however, the most effective approach should be personalized for each patient. Ongoing research is critical to advancing our understanding of TRD and developing more effective therapeutic options.
References
1.Nuñez, N. A., Joseph, B., Pahwa, M., Kumar, R., Resendez, M. G., Prokop, L. J., Veldic, M., Seshadri, A., Biernacka, J. M., Frye, M. A., Wang, Z., & Singh, B. (2022). Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis. Journal of affective disorders, 302, 385–400. https://doi.org/10.1016/j.jad.2021.12.134
2.Caldiroli, A., Capuzzi, E., Tagliabue, I., Capellazzi, M., Marcatili, M., Mucci, F., Colmegna, F., Clerici, M., Buoli, M., & Dakanalis, A. (2021). Augmentative Pharmacological Strategies in Treatment-Resistant Major Depression: A Comprehensive Review. International journal of molecular sciences, 22(23), 13070. https://doi.org/10.3390/ijms222313070
3.Kritzer, M. D., Peterchev, A. V., & Camprodon, J. A. (2023). Electroconvulsive Therapy: Mechanisms of Action, Clinical Considerations, and Future Directions. Harvard review of psychiatry, 31(3), 101–113. https://doi.org/10.1097/HRP.0000000000000365
4.Voineskos, D., Daskalakis, Z. J., & Blumberger, D. M. (2020). Management of Treatment-Resistant Depression: Challenges and Strategies. Neuropsychiatric disease and treatment, 16, 221–234. https://doi.org/10.2147/NDT.S198774
5.Borbély, É., Simon, M., Fuchs, E., Wiborg, O., Czéh, B., & Helyes, Z. (2022). Novel drug developmental strategies for treatment-resistant depression. British journal of pharmacology, 179(6), 1146–1186. https://doi.org/10.1111/bph.15753
6.Ruberto, V. L., Jha, M. K., & Murrough, J. W. (2020). Pharmacological Treatments for Patients with Treatment-Resistant Depression. Pharmaceuticals (Basel, Switzerland), 13(6), 116. https://doi.org/10.3390/ph13060116
7. Rybalko, L., Hulko, T., Yopa, T., Žukow, X., Gorgor, P., Khomenko, E., & Zuków, W. (2024). Using fitness technologies to address post-traumatic stress disorders. Journal of Physical Education and Sport, 24(7), 1569-1581. doi:10.7752/jpes.2024.07177
8. Kverno, K. S., & Mangano, E. (2021). Treatment-Resistant Depression: Approaches to Treatment. Journal of psychosocial nursing and mental health services, 59(9), 7–11. https://doi.org/10.3928/02793695-20210816-01
9. McIntyre, R. S., Rosenblat, J. D., Nemeroff, C. B., Sanacora, G., Murrough, J. W., Berk, M., Brietzke, E., Dodd, S., Gorwood, P., Ho, R., Iosifescu, D. V., Lopez Jaramillo, C., Kasper, S., Kratiuk, K., Lee, J. G., Lee, Y., Lui, L. M. W., Mansur, R. B., Papakostas, G. I., Subramaniapillai, M., … Stahl, S. (2021). Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation. The American journal of psychiatry, 178(5), 383–399. https://doi.org/10.1176/appi.ajp.2020.20081251
10. Pandarakalam J. P. (2018). Challenges of Treatment-resistant Depression. Psychiatria Danubina, 30(3), 273–284. https://doi.org/10.24869/psyd.2018.273
11. Gelenberg, A. J., Freeman, M. P., Markowitz, J. C., Rosenbaum, J. F., Thase, M. E., Trivedi, M. H., & Van Rhoads, R. S. (2010). American Psychiatric Association practice guidelines for the treatment of patients with major depressive disorder. Am J Psychiatry, 167(Suppl 10), 9-118.
12. Kennedy, S. H., Lam, R. W., McIntyre, R. S., Tourjman, S. V., Bhat, V., Blier, P., Hasnain, M., Jollant, F., Levitt, A. J., MacQueen, G. M., McInerney, S. J., McIntosh, D., Milev, R. V., Müller, D. J., Parikh, S. V., Pearson, N. L., Ravindran, A. V., Uher, R., & CANMAT Depression Work Group (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments. Canadian journal of psychiatry. Revue canadienne de psychiatrie, 61(9), 540–560. https://doi.org/10.1177/0706743716659417
13. Carter, B., Strawbridge, R., Husain, M. I., Jones, B. D. M., Short, R., Cleare, A. J., Tsapekos, D., Patrick, F., Marwood, L., Taylor, R. W., Mantingh, T., de Angel, V., Nikolova, V. L., Carvalho, A. F., & Young, A. H. (2020). Relative effectiveness of augmentation treatments for treatment-resistant depression: a systematic review and network meta-analysis. International review of psychiatry (Abingdon, England), 32(5-6), 477–490. https://doi.org/10.1080/09540261.2020.1765748
14. Strawbridge, R., Carter, B., Marwood, L., Bandelow, B., Tsapekos, D., Nikolova, V. L., Taylor, R., Mantingh, T., de Angel, V., Patrick, F., Cleare, A. J., & Young, A. H. (2019). Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis. The British journal of psychiatry : the journal of mental science, 214(1), 42–51. https://doi.org/10.1192/bjp.2018.233
15. Vázquez, G. H., Bahji, A., Undurraga, J., Tondo, L., & Baldessarini, R. J. (2021). Efficacy and Tolerability of Combination Treatments for Major Depression: Antidepressants plus Second-Generation Antipsychotics vs. Esketamine vs. Lithium. Journal of psychopharmacology (Oxford, England), 35(8), 890–900. https://doi.org/10.1177/02698811211013579
16. Zhou, X., Ravindran, A. V., Qin, B., Del Giovane, C., Li, Q., Bauer, M., Liu, Y., Fang, Y., da Silva, T., Zhang, Y., Fang, L., Wang, X., & Xie, P. (2015). Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. The Journal of clinical psychiatry, 76(4), e487–e498. https://doi.org/10.4088/JCP.14r09204
17. Freeman M. P. (2020). Relapse Prevention After Recovery in Patients With Persistent Major Depressive Disorder-An Active Pursuit. JAMA psychiatry, 77(3), 231–232. https://doi.org/10.1001/jamapsychiatry.2019.3637
18. Touloumis C. (2021). The burden and the challenge of treatment-resistant depression. Psychiatrike = Psychiatriki, 32(Supplement I), 11–14. https://doi.org/10.22365/jpsych.2021.046
19. Akil, H., Gordon, J., Hen, R., Javitch, J., Mayberg, H., McEwen, B., Meaney, M. J., & Nestler, E. J. (2018). Treatment resistant depression: A multi-scale, systems biology approach. Neuroscience and biobehavioral reviews, 84, 272–288. https://doi.org/10.1016/j.neubiorev.2017.08.019
20. Lewandowska, J., Pawik, Ł., Pawik, M., Fink-Lwow, F., Kałużny, K., Kałużna, A., & Żukow, W. (2018). Regular yoga exercises and quality of life in women with low back pain-a pilot study.
21. Cladder-Micus, M. B., Speckens, A. E. M., Vrijsen, J. N., T Donders, A. R., Becker, E. S., & Spijker, J. (2018). Mindfulness-based cognitive therapy for patients with chronic, treatment-resistant depression: A pragmatic randomized controlled trial. Depression and anxiety, 35(10), 914–924. https://doi.org/10.1002/da.22788
22. O'Connor, S. J., Hewitt, N., Kuc, J., & Orsini, L. S. (2023). Predictors and Risk Factors of Treatment-Resistant Depression: A Systematic Review. The Journal of clinical psychiatry, 85(1), 23r14885. https://doi.org/10.4088/JCP.23r14885
23. Griffiths, C., da Silva, K. M., Leathlean, C., Jiang, H., Ang, C. S., & Searle, R. (2022). Investigation of physical activity, sleep, and mental health recovery in treatment resistant depression (TRD) patients receiving repetitive transcranial magnetic stimulation (rTMS) treatment. Journal of affective disorders reports, 8, 100337. https://doi.org/10.1016/j.jadr.2022.100337
24. Souza, P. B., de Araujo Borba, L., Castro de Jesus, L., Valverde, A. P., Gil-Mohapel, J., & Rodrigues, A. L. S. (2023). Major Depressive Disorder and Gut Microbiota: Role of Physical Exercise. International journal of molecular sciences, 24(23), 16870. https://doi.org/10.3390/ijms242316870
25. Cui, L., Li, S., Wang, S., Wu, X., Liu, Y., Yu, W., Wang, Y., Tang, Y., Xia, M., & Li, B. (2024). Major depressive disorder: hypothesis, mechanism, prevention and treatment. Signal transduction and targeted therapy, 9(1), 30. https://doi.org/10.1038/s41392-024-01738-y
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Copyright (c) 2025 Monika Makar, Daria Michałka, Zuzanna Gałuszka, Natalie Papachristoforou , Justyna Głowacka, Aleksandra Kocjan, Emilia Bąk, Natalia Tekiela, Radosław Chmiel, Tomasz Bartuś

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