NUR 717 Discussion 2

Major depressive disorder (MDD) is a leading cause of disability worldwide and remains difficult to treat in patients who do not respond to conventional antidepressant therapies. Treatment-resistant depression (TRD) is associated with significant functional impairment, increased healthcare utilization, and elevated suicide risk (Steffens, 2024). As a result, researchers continue to investigate innovative treatment modalities that may improve outcomes for this population. This essay identifies a research article that evaluates a treatment modality for depression and discusses the research methodology, sample size, enrollment criteria, and outcomes, while providing an analysis of the article’s pros and cons and its application to practice.

Methodology, Sample Size, and Enrollment Criteria

The identified study is Glue et al. (2024), a randomized placebo-controlled phase 2 clinical trial evaluating the effectiveness, safety, and tolerability of extended-release ketamine tablets (R-107) in adults with treatment-resistant depression. The study used a multicenter, randomized, double-blind, placebo-controlled phase 2 trial conducted across 20 psychiatric clinics, comprising a 5-day open-label enrichment phase followed by a 12-week double-blind treatment phase. During the enrichment phase, all participants received extended-release ketamine tablets at a dose of 120 mg daily. Participants who demonstrated a treatment response by day 8 were randomized into the double-blind phase.

There were 329 participants screened for eligibility, of whom 231 entered the open-label phase. Of those participants, 168 met the response criteria and were randomized to one of five groups: placebo or extended-release ketamine at doses of 30 mg, 60 mg, 120 mg, or 180 mg, administered twice weekly. Eligible participants were adults aged 18 to 80 years with DSM-5-diagnosed treatment-resistant major depressive disorder and Montgomery–Åsberg Depression Rating Scale (MADRS) scores of ≥20. Participants had failed an average of approximately 4.8 previous antidepressant trials, indicating a highly treatment-resistant population. The primary outcome measured changes in MADRS scores over 13 weeks, demonstrating positive results for extended-release ketamine therapy. Secondary outcomes included remission rates, response rates, relapse prevention, clinical severity measures, adverse events, and overall tolerability.

 Research Analysis

The study employs a rigorous randomized, double-blind, placebo-controlled design, which strengthens internal validity and reduces the likelihood of bias. The multicenter approach also improves generalizability across diverse clinical settings. Additionally, the study examined both efficacy and safety outcomes, providing a comprehensive assessment of the intervention. However, it has several limitations. First, only participants who initially responded to ketamine were randomized into the double-blind phase. This enrichment design may overestimate treatment effectiveness because nonresponders were excluded from later analysis. Second, the study was a phase 2 trial with a relatively modest sample size, which limits its generalizability.

Application to Practice

The study findings have important implications for practice. Extended-release ketamine tablets may provide a more accessible and convenient alternative to intravenous ketamine and intranasal esketamine for patients with treatment-resistant depression. Moreover, since dosing occurred at home during the study, this treatment modality may improve accessibility for patients with transportation, geographic, or scheduling barriers. Psychiatric nurse practitioners should remain informed about emerging ketamine-based therapies, as these interventions may become increasingly integrated into evidence-based treatment plans for patients who fail conventional antidepressant approaches.

Conclusion

Glue et al. (2024) demonstrate that extended-release ketamine tablets are an effective treatment modality for depressive symptoms and relapse rates among adults with treatment-resistant depression. The study has a strong methodology and a favorable safety profile, supporting the potential role of oral ketamine as an innovative treatment modality. Although additional research is needed to evaluate long-term outcomes, this study contributes meaningful evidence supporting the use of ketamine-based therapies in the management of treatment-resistant depression.

References

Glue, P., Loo, C., Fam, J., Lane, H. Y., Young, A. H., Surman, P., & BEDROC study investigators (2024). Extended-release ketamine tablets for treatment-resistant depression: a randomized placebo-controlled phase 2 trial. Nature Medicine, 30(7), 2004–2009. https://doi.org/10.1038/s41591-024-03063-x

Steffens D. C. (2024). Treatment-resistant depression in older adults. The New England Journal of Medicine, 390(7), 630–639. https://doi.org/10.1056/NEJMcp2305428

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Identify one research article (within last five years) that involves evaluation of a treatment modality for either Bipolar 1, Bipolar 2, or depression.  Discuss the methodology of the research, sample size, enrollment criteria, and outcomes.  Provide your analysis of the research article (pros and cons) and application to practice.