High rates of early relapse following electroconvulsive therapy (ECT) are typically reported in the literature. Current treatment guidelines offer little information to clinicians on the optimal nature of maintenance therapy following ECT. The aim of this study was to provide a systematic overview of the existing evidence regarding post-ECT relapse. A keyword search of electronic databases was performed for studies appearing in the peer-reviewed literature before January 2013 reporting on relapse rates in responders to an acute course of ECT administered for a major depressive episode. Meta-analyses were performed where appropriate. Thirty-two studies with up to 2 years' duration of follow-up were included. In modern era studies of continuation pharmacotherapy, 51.1% (95% CI ¼ 44.7-57.4%) of patients relapsed by 12 months following successful initial treatment with ECT, with the majority (37.7%, 95% CI ¼ 30.7-45.2%) relapsing within the first 6 months. The 6-month relapse rate was similar in patients treated with continuation ECT (37.2%, 95% CI ¼ 23.4-53.5%). In randomized controlled trials, antidepressant medication halved the risk of relapse compared with placebo in the first 6 months (risk ratio ¼ 0.49, 95% CI ¼ 0.39-0.62, po0.0001, number needed to treat ¼ 3.3). Despite continuation therapy, the risk of relapse within the first year following ECT is substantial, with the period of greatest risk being the first 6 months. The largest evidence base for efficacy in post-ECT relapse prevention exists for tricyclic antidepressants. Published evidence is limited or non-existent for commonly used newer antidepressants or popular augmentation strategies. Maintenance of well-being following successful ECT needs to be improved.

Objective: ECT is the most effective treatment for severe depression. Previous efficacy studies, using thrice-weekly brief-pulse ECT, reported that high-dose (63 seizure threshold) right unilateral ECT is similar to bitemporal ECT but may have fewer cognitive side effects. The authors aimed to assess the effectiveness and cognitive side effects of twice-weekly moderate-dose (1.53 seizure threshold) bitemporal ECT with high-dose unilateral ECT in real-world practice.Method: This was a pragmatic, patient-and rater-blinded, noninferiority trial of patients with major depression (N=138; 63% female; age=56.7 years [SD=14.8]) in a national ECT service with a 6-month follow-up. Participants were independently randomly assigned to bitemporal or highdose unilateral ECT. The primary outcome was change in the 24-item Hamilton Depression Rating Scale (HAM-D) score after the ECT course; the prespecified noninferiority margin was 4.0 points. Secondary outcomes included response and remission rates, relapse status after 6 months, and cognition.Results: Of the eligible patients, 69 were assigned to bitemporal ECT and 69 to unilateral ECT. High-dose unilateral ECT was noninferior to bitemporal ECT regarding the 24-item HAM-D scores after the ECT course (mean difference=1.08 points in favor of unilateral ECT [95% CI=21.67 to 3.84]). There were no significant differences for response and remission or 6-month relapse status. Recovery of orientation was quicker following unilateral ECT (median=19.1 minutes versus 26.4 minutes). Bitemporal ECT was associated with a lower percent recall of autobiographical information (odds ratio=0.66) that persisted for 6 months.Conclusions: Twice-weekly high-dose unilateral ECT is not inferior to bitemporal ECT for depression and may be preferable because of its better cognitive side-effect profile.

High-dose unilateral ECT does not differ from moderate-dose bitemporal ECT in antidepressant efficacy but has some cognitive advantages.

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Objective Electroconvulsive therapy (ECT) is an effective acute treatment for severe and/or medication‐resistant depression but maintaining remission following completion of a course remains a clinical challenge. Methods EFFECT‐Dep Trial (ISRCTN23577151) participants with a DSM‐IV major depressive episode who met remission criteria after a randomly assigned course of twice‐weekly brief‐pulse bitemporal (1.5 × seizure threshold) or high‐dose (6 × seizure threshold) right unilateral ECT were monitored for relapse for 12 months. In line with the pragmatic trial design, all patients received treatment‐as‐usual individualised pharmacotherapy during and after ECT; no remitter received continuation ECT. Results Of 61 remitters, 24 (39.3%) relapsed, one (1.6%) withdrew from the study while in remission and the remaining 36 (59.0%) stayed well for a year. Most relapses occurred within the first six months, resulting in a cumulative six‐month relapse rate of 31.1%. In a multivariable Cox proportional hazards regression model, older age (p = 0.039) and psychotic features at pre‐ECT baseline (p = 0.037) were associated with a more favourable long‐term prognosis while a greater number of previous depressive episodes (p = 0.028) and bipolar II (but not bipolar I) diagnosis (p = 0.030) were associated with a worse long‐term outcome. Electrode placement and medication resistance prior to ECT had no effect on relapse. Adjusting for covariates, fewer patients treated with lithium relapsed in the overall group (p = 0.008) and in the unipolar depression subgroup (p = 0.027). Conclusion Long‐term outcome following high‐dose right unilateral ECT does not differ from bitemporal ECT. Prognosis is particularly favourable in older adults, psychotic depression and patients maintained on lithium.

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, yet its mechanism of action is not fully understood. Peripheral blood proteomic analyses may offer insights into the molecular mechanisms of ECT. Patients with a major depressive episode were recruited as part of the EFFECT-Dep trial (enhancing the effectiveness of electroconvulsive therapy in severe depression; ISRCTN23577151) along with healthy controls. As a discovery-phase study, patient plasma pre-/post-ECT (n=30) was analyzed using 2-dimensional difference in gel electrophoresis and mass spectrometry. Identified proteins were selected for confirmation studies using immunodetection methods. Samples from a separate group of patients (pre-/post-ECT; n=57) and matched healthy controls (n=43) were then used to validate confirmed changes. Target protein mRNA levels were also assessed in rat brain and blood following electroconvulsive stimulation (ECS), the animal model of ECT. We found that ECT significantly altered 121 protein spots with 36 proteins identified by mass spectrometry. Confirmation studies identified a post-ECT increase (P<0.01) in the antiangiogenic and neuroprotective mediator pigment epithelium-derived factor (PEDF). Validation work showed an increase (P<0.001) in plasma PEDF in depressed patients compared with the controls that was further increased post-ECT (P=0.03). PEDF levels were not associated with mood scores. Chronic, but not acute, ECS increased PEDF mRNA in rat hippocampus (P=0.02) and dentate gyrus (P=0.03). This study identified alterations in blood levels of PEDF in depressed patients and further alterations following ECT, as well as in an animal model of ECT. These findings implicate PEDF in the biological response to ECT for depression.

We found reduced specificity of episodic autobiographical memory in depressed patients before ECT, which persisted at long-term follow-up despite significant improvement in mood. The finding of no detectable retrograde amnesia likely reflects lack of sensitivity of the recent life section of the AMI to detect ECT-induced changes.

An error was included in Fig 3 of the above article. The data for item 3.1 Reorientation time were mistakenly switched around with regards to the Bitemporal and Unilateral groups. The corrected Figure 3 is presented below. The results are otherwise correct and conclusions unchanged. The authors would like to apologise for this error.