Short Communication

Therapeutic Strategies in Treatment-Resistant Depression: Myths and Evidence

Laura Prieto-Arenas¹, Sofia Belló-Pérez¹, Laura Huerta-Melús¹, Sheila Fernández-Navarro¹, Raquel Brinquis-Seco¹ and M Carmen Arenas²*

¹Hospital Obispo Polanco, Spain

²Faculty of Psychology, University of Valencia, Spain

Submission: February 17, 2023; Published: March 02, 2023

*Corresponding author: M Carmen Arenas, Hospital Obispo Polanco, Av. Ruiz Jarabo, Faculty of Psychology, University of Valencia, Avda. Blasco Ibañez, 21, 46010 Valencia, Spain

How to cite this article:Laura Prieto-Arenas, Sofia Belló-Pérez, Laura Huerta-Melús, Sheila Fernández-Navarro, Raquel Brinquis-Seco and M Carmen Arenas. Therapeutic Strategies in Treatment-Resistant Depression: Myths and Evidence. JOJ Pub Health. 2023; 7(3): 555713. DOI: 10.19080/JOJPH.2023.07.555713

Keywords: Psychiatrist; Depressive disorders; Psychiatric disorders; Pathology; Deep brain stimulation; Ketamine; Intranasal esketamine

Short Communication

Treatment-resistant depression (TRD) is a challenge for psychiatrists. It is a disorder with a high prevalence, since approximately 30% of patients with depression do not respond to any treatment [1,2]. This may be due to two main factors, namely the union of several subtypes of depressive disorders and the coexistence of other psychiatric disorders [3]. Therefore, the diagnosis of TRD is complicated. Although there is no clear consensus among researchers to define diagnostic criteria of TRD [2-4], it appears that the most accepted definition is the non-response to two or more antidepressants at appropriate times and doses [5]. Due to the low consensus regarding the criteria for its diagnosis and the great variability of its evolution, on many occasions this pathology is diagnosed late and its treatment is very lengthy. This has a major impact on the patient’s quality of life, constituting a major risk factor for suicide [6], and it also affects the global health economy.

Given the lack of response described, the introduction of adjuvant treatments is usually necessary, among which we can highlight the use of second generation antipsychotics, lithium or thyroid hormone [4]. Other possible non-pharmacological strategies include psychotherapy, transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) [7].

ECT, despite being a technique that has shown high effectiveness and speed in its performance in the management of TRD, is far from perfect. In many cases it requires sessions maintained over time, not relieving the patient of the risks posed by the use of general anesthesia. In addition, possible side effects to this technique include memory loss [8,9]. We cannot forget the stigma that accompanies it, derived from the bad press it has received in books, films and the media in the past. All this means that on multiple occasions it outright generates rejection in patients and relatives. Other alternatives that are beginning to look promising are vagus nerve stimulation (VNS) and deep brain stimulation. However, more studies are needed to ensure their effectiveness [8].

Among the new therapies to consider with great preliminary results, we can highlight the use of intravenous ketamine and, more recently, intranasal esketamine [10,11]. However, although the compassionate use of ketamine/esketamine is a novel approach and increasingly more studies confirm its effectiveness in TRD, it should not be forgotten that it is an abuse substance and that, therefore, its administration may precipitate abuse or sensitization towards other drugs [12] Thus, there is still some uncertainty about which step it should occupy in therapeutic algorithms. Studies indicate the need for repeated use or high doses [13], and at present, there are insufficient data on its long-term safety and tolerability [14].

The importance of different psychological therapies as adjunctive treatment should be emphasized. Although several studies indicate that no therapy is superior to another in its overall efficacy, all authors agree that it is a key element in the therapeutic approach of this disease. More studies are needed to determine which psychotherapy is most appropriate according to the characteristics of each patient [15].

In short, knowing the most suitable therapeutic strategy for each patient remains uncertain at present, since there is a lack of studies regarding the clinical, genetic and sociodemographic variables associated with therapeutic failure. It is necessary to emphasize the importance of having a good approach from the beginning by detecting the risk factors and characteristics of the patient early, since when TRD is prolonged over time, the individual ends up accepting it as part of their identity and, consequently, it ends up adversely affecting their quality of life and their social and working environment.

References

1. McLachlan G (2018) Treatment resistant depression: what are the options? 363: k5354.
2. Gaynes BN, Lux L, Gartlehner G, Asher G, Forman-Hoffman V, et al. (2020) Defining treatment-resistant depression. Depress Anxiety 37(2): 134-145.
3. Rybak YE, Lai KSP, Ramasubbu R, Vila-Rodriguez F, Blumberger DM, et al. (2021) Treatment-resistant major depressive disorder: Canadian expert consensus on definition and assessment. Depress Anxiety 38(4): 456-467.
4. Voineskos D, Daskalakis ZJ, Blumberger DM (2020) Management of treatment-resistant depression: Challenges and strategies. Neuropsychiatr Dis Treat 16: 221-234.
5. Conway CR, George MS, Sackeim HA (2017) Toward an evidence-based, operational definition of treatment-resistant depression: When Enough is Enough. JAMA Psychiatry 74(1): 9-10.
6. Bergfeld IO, Mantione M, Figee M, Schuurman PR, Lok A, et al. (2018) Treatment-resistant depression and suicidality. J Affect Disord 235: 362-367.
7. Boland R, Verduin ML (2022) Other somatic therapies. In: Synopsis of psychiatry Kaplan & Sadock. (12^th edn). Wolters Kluwer, Netherlands, Europe, pp. 729-744.
8. Pandarakalam JP (2018) Challenges of treatment-resistant depression. Psychiatr Danub 30(3): 273-284.
9. Veraart JKE, Smith-Apeldoorn SY, Spaans HP, Kamphuis J, Schoevers RA (2020) Is ketamine an appropriate alternative to ECT for patients with treatment resistant depression? A systematic review. J Affect Disord 281: 82-89.
10. Popova V, Daly EJ, Trivedi M, Cooper K, Lane R, et al. (2019) Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: A randomized double-blind active-controlled study. Am J Psychiatry 176(6): 428-438.
11. Tuta E, Acero A, León M, López M, Prieto V, et al. (2022) Ketamine for refractory depression: an exploratory review. Spanish Psychiatric Proceedings 50(2): 144-159.
12. Singh I, Morgan C, Curran V, Nutt D, Schlag A, et al. (2017) Ketamine treatment for depression: opportunities for clinical innovation and ethical foresight. Lancet Psychiatry 4(5): 419-426.
13. McIntyre RS, Carvalho IP, Lui LMW, Majeed A, Masand PS, et al. (2020) The effect of intravenous, intranasal, and oral ketamine in mood disorders: A meta-analysis. J Affect Disord 276: 576-584.
14. McIntyre RS, Rosenblat JD, Nemeroff CB, Sanacora G, Murrough JW, et al. (2021) Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: An international expert opinion on the available evidence and implementation. Am J Psychiatry 178(5): 383-399.
15. Van Bronswijk S, Moopen N, Beijers L, Ruhe HG, Peeters F (2019) Effectiveness of psychotherapy for treatment-resistant depression: a meta-analysis and meta-regression. Psychol Med 49(3): 366-379.