Effects of ketamine in electroconvulsive therapy for major depressive disorder: meta-analysis of randomised controlled trials

Abstract

BackgroundThe use of ketamine in electroconvulsive therapy (ECT) has been examined in the treatment of major depressive disorder (MDD); however, there has been no systematic review and meta-analysis of related randomised controlled trials (RCTs).AimTo examine the efficacy and safety of ketamine augmentation of ECT in MDD treatment.MethodsTwo reviewers searched Chinese (China National Knowledge Infrastructure and Wanfang) and English (PubMed, PsycINFO, Embase and Cochrane Library) databases from their inception to 23 July 2019. The included studies' bias risk was evaluated using the Cochrane risk of bias assessment tool. The primary outcome of this meta-analysis was improved depressive symptoms at day 1 after a single ECT treatment session. Data were pooled to calculate the standardised mean difference and risk ratio with their 95% CIs using RevMan V.5.3. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the whole quality of evidence.ResultsFour RCTs (n = 239) compared ketamine alone or ketamine plus propofol (n = 149) versus propofol alone (n = 90) in patients with MDD who underwent a single ECT session. Three RCTs were considered as unclear risk with respect to random sequence generation using the Cochrane risk of bias. Compared with propofol alone, ketamine alone and the combination of ketamine and propofol had greater efficacy in the treatment of depressive symptoms at days 1, 3 and 7 after a single ECT session. Moreover, compared with propofol alone, ketamine alone and the combination of ketamine and propofol were significantly associated with increased seizure duration and seizure energy index. Compared with propofol, ketamine alone was significantly associated with increased opening-eye time. Based on the GRADE approach, the evidence level of primary and secondary outcomes ranged from very low (26.7%, 4/15) to ‘low’ (73.3%, 11/15).ConclusionCompared with propofol, there were very low or low evidence levels showing that ketamine alone and the combination of ketamine and propofol appeared to rapidly improve depressive symptoms of patients with MDD undergoing a single ECT session. There is a need for high-quality RCTs.

Efficacy and Safety of Ketamine-assisted Electroconvulsive Therapy in Major Depressive Episode: A Systematic Review and Network Meta-Analysis

“…One previous study performed a pairwise meta-analysis on ketamine versus propofol versus ketamine plus propofol using three RCTs, 60 and concluded that ketamine alone and the combination of ketamine and propofol had greater efficacy in the treatment of depressive symptoms. However, this study only considered a single ECT session and excluded studies with two or more ECT sessions.…”

Assessment of effect of propofol and ketamine in electroconvulsive therapy anesthesia

“…No significant differences were found on any outcome measure during, at the end of or 1 month following the ECT course. Li XM et al [8] examined the efficacy and safety of ketamine augmentation of ECT in MDD treatment. Four RCTs (n = 239) compared ketamine alone or ketamine plus propofol (n = 149) versus propofol alone (n = 90) in patients with MDD who underwent a single ECT session.…”

Ketamine in depression and electroconvulsive therapy

“…Overall, no added benefit in the depression scores has been observed at the end of the index course ECT performed under ketamine anesthesia [109][110][111]. On the other hand, ketamine has been shown to provide better seizure quality regardless of the administered dose, compared with nonketamine anesthesia [111].…”