Adverse Effects of Esketamine for the Treatment of Major Depression Disorder: Findings from Randomized Controlled Trials

Abstract

Esketamine is a promising drug which can induce antidepressant effects in Major Depression Disorder (MDD). Several randomized controlled trials (RCTs) have been implemented to assess the efficacy and safety of esketamine for the treatment of MDD. Therefore, we carried out a meta-analysis to assess adverse effect profiles of esketamine for the treatment of MDD. We searched RCTs which were implemented from January 2010 to June 2020 by searching PubMed, Embase and Cochrane Library databases. Finally, four RCTs with 551 patients were included in our study. We pooled 551 patients from 4 RCTs. Compared with placebo, an increased risk of adverse effects was observed in our analysis. After using esketamine, the risk of nausea (RR = 2.34, 95% CI, 1.04 to 5.25, P = 0.04), dissociation (RR = 4.54, 95% CI, 2.36 to 8.73, P < 0.00001), dizziness (RR = 3.00, 95% CI, 1.80 to 5.00, P < 0.0001), vertigo (RR = 7.47, 95% CI, 2.55 to 21.86, P = 0.0002), hypoesthesia (RR = 5.68, 95% CI, 2.06 to 15.63, P = 0.0008), sedation (RR = 3.96, 95% CI, 1.29 to 12.15, P = 0.02) and paresthesia(RR = 3.05, 95% CI, 1.07 to 8.65, P = 0.04)were significantly increased compared with placebo. Our synthesized data analysis revealed drug specific risk profiles. The most frequent adverse effects under treatment with esketamine were nausea, dissociation, dizziness, vertigo, hypoesthesia,sedation and paresthesia.

Results of esketamine administration in a Greek population; a case series

“…8,9,21,22 Several studies have examined the side effects associated with the intake of esketamine. 21,23,24 Our patients experienced mild and transient side effects, mainly in the first hour after the infusion and during the induction phase. Side effects became less frequent as the treatment continued.…”

Facts and myths about use of esketamine for treatment-resistant depression: a narrative clinical review

“…The meta-analysis by Yang et al. ( 82 ) found an overall relative risk of developing dissociation of 4.54 ( p <.00001) among patients using esketamine when compared with placebo group. This value resulted almost twice (RR: 8.06, p <.00001) in the subgroup taking the dosage of 56 mg.…”

“…It encompasses depersonalization, derealization, illusions and distortion of time, which may be experienced within a few hours and mostly at a non-severe degree by 11.1-31.4% of people treated with esketamine (28). The metaanalysis by Yang et al (82) found an overall relative risk of developing dissociation of 4.54 (p<.00001) among patients using esketamine when compared with placebo group. This value resulted almost twice (RR: 8.06, p<.00001) in the subgroup taking the dosage of 56 mg.…”

Mitochondrial Metabolism in Major Depressive Disorder: From Early Diagnosis to Emerging Treatment Options

“…However, the persistence of the antidepressant effect in the medium and long term is a topic of debate in the literature. Some studies have found that the improvement observed during the induction phase with esketamine is maintained during the maintenance phase [ 71 ], while others report that the benefits may not be as consistent over time [ 78 , 79 ]. These discrepancies may be due to differences in study design and the heterogeneity of the patient sample, highlighting the need for more research in this area.…”