2Analysis of Articles

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1 Effectiveness of Esketamine in Treating Depression: Analysis of Articles Name University PSYCH Prof. January 2024

2 Effectiveness of Esketamine in Treating Depression: Analysis of Articles 1.0. Introduction 1.1. Topic Areas In 2019, the FDA approved Esketamine, derived from a potential anaesthetic, Ketamine, to treat treatment-resistant depression (TRD) among adults. Unlike conventional anti-depressants that increase the levels of naturally occurring chemicals in the brain, Esketamine works by optimizing the synapse's plasticity by modulating glutamate (Vasiliu, 2023). This paper aims to scan the existing research on the effectiveness of Esketamine in treating depression, focusing on five articles. 1.2. Search Strategy The articles were located in four reputed databases: PubMed, Google Scholar, National Library of Medicine, and ProQuest. The articles were located by mainly relying on the following key phrases or search queries:  "Effectiveness of Esketamine in treating depression”  "Effects of Esketamine on patients with depression”  “Results of using Esketamine for depressive symptoms”  “Esketamine and depression/depressive symptoms” 2.0. Article One 2.1. Research Methods The first research article by Vasiliu (2023) reviewed for this paper is based on a narrative review focusing on 14 existing research articles retrieved from different databases. 2.2. Phenomena of Interest The article under consideration aims to analyze the long-term impact of Esketamine on patients with treatment-resistant depression and compare it with the findings of short-term trials (Vasiliu, 2023).

3 2.3. Findings Relying on the data from the sample studies, the researcher has found that while Esketamine has proven evidence of effectiveness in the short term, the findings about long- term favourable or adverse impacts are mixed. Besides, the existing data does not provide adequate grounds to reach generalizable conclusions. 2.4. Safety and Ethical Considerations The researcher has properly acknowledged the contribution of all the studies and supplementary material used to obtain the information. Besides, the limitations, such as the limited data availability, have been properly acknowledged to ensure academic integrity. 3.0. Article Two 3.1. Research Methods The second research article by Herrera-Imbroda (2023) is also based on a narrative analysis of the existing literature using a mix of placebo-controlled and open-label studies. The researcher has collected the relevant studies specifically from PubMed and analysis using narrative synthesis. 3.2. Key Variables or Phenomena of Interest The article uses evidence from existing research to determine the degree to which esketamine-based nasal sprays help relieve TRD in the long term. 3.3. Findings The researcher has found that both types of studies support the drug's long-term efficacy for patients with TRD (Herrera-Imbroda). 3.4. Safety and Ethical Considerations The researcher has properly acknowledged the contributions to the research through appropriate citations and referencing conventions. Besides, the researcher acknowledges that

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4 the absence of a systematic review and analysis affects the generalizability of existing research. 4.0. Article Three 4.1. Research Methods The article by Reif et al. (2023) is based on primary research synthesized with existing literature. The sample population comprises groups of patients with depressive symptoms who have been resistant to previous treatment options. The researchers have administrated the doses of drugs to be compared among 336 patients, keeping the raters blind to the specifications. The doses were administrated randomly using an open-label approach using a 1:1 ratio for each drug: Esketamine and Quetiapine. The findings are statistically evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS) to assess the remission rate and sustainability of effects for 32 weeks for each group: the Esketamine group and the Quetiapine group. 4.2. Key Variables or Phenomena of Interest The study aims to compare the short-term and long-term effectiveness of Esketamine in depression with Quetiapine, another anti-depressant used for TRD. 4.3. Findings The findings suggest that the Esketamine group showed a greater remission rate on both stages than Quetiapine, emerging as a more promising alternative. 4.4. Safety and Ethical Considerations The researchers did not disclose the purpose of the study to the population, lacking the element of informed consent. The safety concerns are attached to two choices: using flexible doses (with no clear guidelines) and administrating the doses despite the lack of evidence about their adverse impact.

5 5.0. Article Four 5.1. Research Methods The article by McIntyre (2021) is based on existing literature about the use of Ketamine and Esketamine for TRD patients. The findings are interpreted to create guidelines for the practitioners. 5.2. Key Variables or Phenomena of Interest The study aims to create guidelines regarding the efficacy, tolerability, and safety concerns for using drugs above to treat TRD. 5.3. Findings The findings indicate that while both drugs have shown promising results during clinical trials, as proven by existing literature, more research is needed to ascertain their long- term implications. Similarly, there is a lack of clarity on the side effects, which raises safety hazards regarding administering Esketamine at a large scale (McIntyre, 2021). 5.4. Safety and Ethical Considerations While the study relies on existing literature, the guidelines and conclusions are opinion-based. However, the researchers have properly acknowledged secondary sources through appropriate citation and referencing conventions. 6.0. Article Five 2.1. Research Methods The research article by Martinotti et al. (2022) is based on an observational, multi- centric, and retrospective study of 116 TRD patients who had ESKETamine administrated. Patients' medical records were compared for the follow-ups at two stages: one month and three months. The anamnestic and psychometric scales were used to observe the effectiveness of treatment.

6 2.2. Key Variables or Phenomena of Interest The study aimed to compare the effectiveness of Eskatime nasal spray between pre- and post-assessment periods for each one and three-month trial, along with any potential side effects. 2.3. Findings The findings suggest that the number of remissions was significantly higher for a one- month follow-up than three months compared to the pre-assessment. No potential side effects were observed. 2.4. Safety and Ethical Considerations Since the researchers aimed to give the study a real-world touch, it was inappropriate to gain informed consent. However, the risk was minimized using proper protocols for the safe administration of the drug.

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7 References Herrera-Imbroda, J. (2023). Changing the paradigm in treatment-resistant depression: A review of long-term efficacy and tolerability of esketamine nasal spray. Experimental and Clinical Psychopharmacology , 31 (6), 1092-1101. https://doi.org/10.1037/pha0000650 Martinotti, G., Vita, A., Fagiolini, A., Maina, G., Bertolino, A., Dell'Osso, B., Siracusano, A., Clerici, M., Bellomo, A., Sani, G., D'Andrea, G., Chiaie, R. D., Conca, A., Barlati, S., Di Lorenzo, G., De Fazio, P., De Filippis, S., Nicolò, G., Rosso, G., … Di Giannantonio, M. (2022). Real-world experience of esketamine use to manage treatment-resistant depression: A multicentric study on safety and effectiveness (REAL-ESK study). Journal of Affective Disorders , 319 , 646-654. https://doi.org/10.1016/j.jad.2022.09.043 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 Reif, A., Bitter, I., Buyze, J., Cebulla, K., Frey, R., Fu, D. J., Ito, T., Kambarov, Y., Llorca, P. M., Oliveira-Maia, A. J., Messer, T., Mulhern-Haughey, S., Rive, B., von Holt, C., Young, A. H., Godinov, Y., & ESCAPE-TRD Investigators (2023). Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression. The New

8 England journal of medicine , 389 (14), 1298–1309. https://doi.org/10.1056/NEJMoa2304145 Vasiliu, O. (2023). Esketamine for treatment-resistant depression: A review of clinical evidence (Review). Experimental and Therapeutic Medicine , 25 (3). https://doi.org/10.3892/etm.2023.11810

2Analysis of Articles

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