Long-Term Efficacy of Intranasal Esketamine in Treatment-Resistant Major Depression: A Systematic Review

Abstract

Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed.

Global Trends and Hotspots in Esketamine Research: A Bibliometric Analysis of Past and Estimation of Future Trends

“…In recent years, traditional reviews and meta-analyses have been conducted to systematically examine esketamine research from various aspects. 10–12 However, a bibliometric analysis that comprehensively shows the status and trends of this field has not yet been performed. Thus, we aimed to determine general information regarding publications in esketamine research, such as the most productive and influential countries or regions, institutions, authors, and journals, according to the number of publications or citations.…”

Augmentative Pharmacological Strategies in Treatment-Resistant Major Depression: A Comprehensive Review

“…Continued esketamine treatment following the induction phase may be associated with stable efficacy in relapse prevention among TRD patients [ 101 , 103 ]. However, the long-term antidepressant and anti-suicidal effects of esketamine after discontinuation might be inconsistent [ 134 ]. Indeed, TRD has a chronic course, poor clinical stabilization, and high suicidal risk, and, therefore, to date, it is difficult to know whether clinicians should continue to use esketamine after the acute episode, for how long, at which dose, and in which patients.…”

Efficacy of an adjuvant non-face-to-face multimodal lifestyle modification program for patients with treatment-resistant major depression: A randomized controlled trial

“…Successful treatment of TRD may require different biomedical methods, such as combinations of psychopharmacological agents, brain neurostimulation techniques, and even powerful new drugs such as ketamine (Capuzzi et al, 2021;Nuñez et al, 2022). However, these treatments can have problems of acceptance, tolerance, and safety, and there is also the problem of maintaining long-term efficacy (Eduardo et al, 2022).…”