Systematic review on relapse-prevention strategies following successful electroconvulsive therapy for major depressive disorder

Background Electroconvulsive therapy (ECT) is highly effective for major depressive disorder (MDD), but about 50% of patients relapse within 1 year. A comprehensive review of all potential relapseprevention strategies is lacking. Aims This systematic review aimed to identify, summarise and critically evaluate the available evidence on pharmacological, neuromodulatory, psychological and combination strategies to prevent relapse following successful ECT for MDD. Method A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO: no. CRD42023392575). We searched PubMed, Embase, PsychInfo and Cochrane Library up to March 2025. Eligible studies included adults (>18 years) with unipolar MDD who responded to acute ECT and were followed for ≥3 months. We included randomised controlled trials (RCTs), cohort studies and case series (over ten cases). Risk of bias and quality were assessed and a narrative synthesis conducted. Results A total of 28 studies (N = 11 119) were included. Lithium (alone or with antidepressants) was most consistently associated with reduced relapse in 10 studies. Continuation ECT (C-ECT), particularly when combined with pharmacotherapy, also reduced relapse in several RCTs. Evidence for psychotherapy (e.g. cognitive–behavioural therapy) is limited (two studies), warranting further studies. No studies on repetitive transcranial magnetic stimulation or ketamine were found. Study quality varied, with some being underpowered or having used inconsistent definitions of relapse. Conclusions Pharmacotherapy with lithium and, separately, C-ECT combined with medication, showed the strongest evidence for relapse prevention following ECT. The evidence base is limited by heterogeneity, small sample sizes and few studies on novel or psychological strategies. More robust clinical studies are needed to identify optimal long-term strategies.