A large number of people worldwide grapple with Major Depressive Disorder (MDD), and a significant portion of them confront resistance to conventional antidepressant treatments. Esketamine, an innovative intervention, has garnered attention due to its rapid-acting antidepressant effects. This meta-analysis aimed to evaluate the efficacy and safety of esketamine in individuals with MDD and Treatment-Resistant Depression (TRD). We performed an extensive search of electronic databases, including PubMed, EMBASE, and Cochrane Library, covering the period from inception to January 15, 2024, to identify clinical trials investigating the efficacy, safety, and tolerability of esketamine in individuals with MDD and TRD. Meta-analyses were conducted using a random-effect model, with the risk ratio (RR) chosen as the effect size. After screening, nine studies met inclusion criteria comprising 1752 patients. Esketamine dosages varied from 28 to 84 mg, administered intranasally in conjunction with an oral antidepressant. Intranasal esketamine exhibited significantly higher remission rates compared to the placebo (RR = 1.371, 95% CI: 1.194 to 1.574, p < 0.0001). Subgroup analysis revealed that the 84 mg and flexible doses were particularly effective. Moreover, intranasal esketamine demonstrated higher response rates compared to the placebo (RR = 1.274, 95% CI: 1.108 to 1.465, p-value = 0.001). Although adverse events were common in the esketamine group, they were generally tolerable. Intranasal esketamine demonstrated effectiveness in reducing scores among patients with MDD and TRD. The drug exhibited both safety and tolerability. However, further research is warranted to investigate its long-term effects and efficacy in specific patient subgroups.
