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The prevalence of major depression declines with age, but depressive symptoms become more common. Never normal, these are eminently treatable with antidepressants taken in adequate dosages for an appropriate length of time. [ABSTRACT FROM AUTHOR]

Competing Interests: Conflicts of Interest and Source of Funding: Dr. Kellner receives fees from UpToDate for writing/editing ECT topics, royalties from Cambridge University Press for Handbook of ECT (2019), and fees from Northwell Health for teaching in an ECT course.

Abstract: Major depressive disorder (MDD) is a highly prevalent and disabling condition. As such, understanding the causes of and treatment options for MDD is critical. Electroconvulsive therapy (ECT) remains the gold standard depression treatment, but the molecular mechanisms that underlie its effects are still largely unknown. One such explanation hinges on the immuno-inflammatory correlates of ECT treatment, given mounting evidence supporting the inflammatory hypothesis of depression. This review aims to provide an overview of the suggested immunomodulatory effects of ECT and the predictive value of immune biomarkers in relation to treatment outcomes and side effects. We conducted a preregistered, systematic literature search utilizing MEDLINE (PubMed), Embase (Elsevier), and PsycINFO (EBSCO) databases. We employed keywords related to MDD, ECT, gut microbiome, and the immune system. We only included human subjects research published between 1985 and January 13, 2021. Twenty-six unique studies were included in our analyses. Findings indicate a proinflammatory profile associated with MDD, with immune biomarkers exhibiting acute and chronic changes following ECT. Consistently, lower baseline interleukin 6 levels and higher C-reactive protein levels are correlated with a greater reduction in depressive symptoms following ECT. Furthermore, included studies emphasize the predictive value of peripheral immune changes, specifically interleukin 6 and tumor necrosis factor α, on cognitive outcomes following ECT. Given these results, further exploration of the potential roles of immunomodulatory effects on ECT treatment outcomes, as well as adverse cognitive side effects, is indicated., Competing Interests: Conflicts of interest and source of funding: J.R.Y. receives funding from VA Career Development Awards (CDA-1, CDA-2), Clinical Science Research and Development Service (CSR&D): 1 IK1 CX002187-01A1 , 1 IK2 CX002610-01 ; Department of Veterans Affairs (VA) Mid-Atlantic Mental Illness Research, Education, and Clinical Center, Durham VA Health Care System; Duke University Department of Psychiatry and Behavioral Sciences; Duke Interdisciplinary Studies Bass Connections. American Society of Clinical Psychopharmacology and International Society for ECT and Neurostimulation (ISEN) also provided J.R.Y. with support for this work. M.K.E. is supported by the Durham VA Health Care System and Duke University Department of Psychiatry and Behavioral Sciences. M.K. received funding from MGH Training Grant Translational Neuroscience Training for Clinicians (T32MH112485) and the Harvard Medical School Department of Psychiatry Dupont Warren Grant. C.H.K. receives royalties from Cambridge University Press for Handbook of ECT , fees from UpToDate for writing/editing sections on ECT, and fees from Northwell Health for teaching in an ECT course. For the remaining authors, none were declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Electroconvulsive therapy (ECT) can be life-saving in situations where patients are at risk of dying from severe manifestations of psychiatric illness. In some of these cases, patients are unwilling/unable to consent to ECT, and involuntary ECT is required. Such use of involuntary ECT varies substantially across European countries for unclear reasons. The aim of this study was to examine clinical and legal differences in this use of involuntary ECT across European countries., Methods: A questionnaire based on a case vignette (a 55-year-old female inpatient with psychotic depression at imminent risk of dying from metabolic derangement because of refusal to eat and drink) was sent to an ECT practitioner in each of 31 European countries., Results: We received responses from ECT practitioners in 18 countries. In 7 of these countries, involuntary ECT could be carried out without approval from others and/or involvement of the court system in the case described in the vignette. Practitioners in the remaining 11 countries responded that they either could not carry out involuntary ECT or would have to meet certain requirements before initiating involuntary ECT (e.g., approval from medical/ethics committee and second opinion from an independent psychiatrist). Notably, the rules regarding involuntary ECT differed for adults and minors (more restrictive for the latter) in 6 of the 18 countries., Conclusions: In many European countries, legislation precludes or delays the use of involuntary ECT. Harmonization of the legislation on involuntary ECT across European countries to allow for better access to this potentially life-saving treatment seems warranted., Competing Interests: Conflicts of interest: C.H.K. reports personal fees from UpToDate, Cambridge University Press, Northwell Health, and Psychiatric Times. In addition, C.H.K. has a patent for a bite block for protecting the mouth of patients receiving electroconvulsive therapy (US6098627A). S.D.Ø. received the 2020 Lundbeck Foundation Young Investigator Prize. Furthermore, S.D.Ø. owns/has owned units of mutual funds with stock tickers DKIGI, IAIMWC, SPIC25KL, and WEKAFKI, and has owned units of exchange-traded funds with stock tickers BATE, TRET, QDV5, QDVH, QDVE, SADM, IQQH, USPY, EXH2, 2B76, and EUNL., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To meta-analyze clinical efficacy and safety of ketamine compared with other anesthetic agents in the course of electroconvulsive therapy (ECT) in major depressive episode (MDE)., Methods: PubMed/MEDLINE, Cochrane Library, Embase, GoogleScholar, and US and European trial registries were searched from inception through May 23, 2023, with no language limits. We included RCTs with (1) a diagnosis of MDE; (2) ECT intervention with ketamine and/or other anesthetic agents; and (3) measures included: depressive symptoms, cognitive performance, remission or response rates, and serious adverse events. Network meta-analysis (NMA) was performed to compare ketamine and 7 other anesthetic agents. Hedges' g standardized mean differences (SMDs) were used for continuous measures, and relative risks (RRs) were used for other binary outcomes using random-effects models., Results: Twenty-two studies were included in the systematic review. A total of 2322 patients from 17 RCTs were included in the NMA. The overall pooled SMD of ketamine, as compared with propofol as a reference group, was -2.21 (95% confidence interval [CI], -3.79 to -0.64) in depressive symptoms, indicating that ketamine had better antidepressant efficacy than propofol. In a sensitivity analysis, however, ketamine-treated patients had a worse outcome in cognitive performance than propofol-treated patients (SMD, -0.18; 95% CI, -0.28 to -0.09). No other statistically significant differences were found., Conclusions: Ketamine-assisted ECT is tolerable and may be efficacious in improving depressive symptoms, but a relative adverse impact on cognition may be an important clinical consideration. Anesthetic agents should be considered based on patient profiles and/or preferences to improve effectiveness and safety of ECT use., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Electroconvulsive therapy (ECT) is one of the most effective and rapid-acting treatment for severe depression but is associated with cognitive side-effects. Identification of add-on treatments that counteract these side-effects would be very helpful. This randomized, double-blinded, placebo-controlled, parallel-group study investigated the effects of four add-on erythropoietin (EPO; 40,000 IU/ml) or saline (placebo) infusions over 2.5 weeks of ECT (eight ECT sessions) in severely depressed patients with unipolar or bipolar depression. Neuropsychological assessments were conducted pre-ECT, three days after the eighth ECT (week 4), and at a 3-month follow-up. Further, functional magnetic resonance imaging (fMRI) was conducted after the eighth ECT. The primary outcome was change from pre- to post-ECT in a 'speed of complex cognitive processing' composite. Secondary outcomes were verbal and autobiographical memory. Of sixty randomized patients, one dropped out before baseline. Data were thus analysed for 59 patients (EPO, n = 33; saline, n = 26), of whom 28 had fMRI data. No ECT-related decline occurred in the primary global cognition measure (ps≥0.1), and no effect of EPO versus saline was observed on this outcome (ps≥0.3). However post-ECT, EPO-treated patients exhibited faster autobiographical memory recall than saline-treated patients (p = 0.02), which was accompanied by lower memory-related parietal cortex activity. The absence of global cognition changes with ECT and EPO, coupled with the specific impact of EPO on autobiographical memory recall speed and memory-related parietal cortex activity, suggests that assessing autobiographical memory may provide increased sensitivity in evaluating and potentially preventing cognitive side-effects of ECT. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT03339596, EudraCT no.: 2016-002326-36., Competing Interests: Declaration of Competing Interest KWM has received consultancy fees from Lundbeck, Janssen, Angelini Pharma and Gedeon Richter in the past three years. JZP has within the last three years received honoraria from Lundbeck Pharma A/S. MV has within the last three years received consultancy fees from Janssen Cilag and Lundbeck. LVK has within recent three years been a consultant for Lundbeck and Teva. CHK receives honoraria from Cambridge University Press, and fees from UpToDate and Northwell Health. JMAC, KC, IAL, ATYN, MBM, HE, IH, PV, KG, LGH, JLJ, and MBJ report no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

1. Two recent clinical trials, KetECT and ELEKT-D, compared the effectiveness of ketamine and electroconvulsive therapy (ECT) for major depressive disorder. Notably, these trials reported marked differences in ECT's clinical outcomes of, with remission rates of 63% for KetECT and a strikingly lower rate of 22% for ELEKT-D, while the remission rates for ketamine were 46% and 38%, respectively. Considering that the primary objective of both trials was to compare the standard treatment (ECT) with an experimental intervention (ketamine), it is crucial to highlight the pronounced disparities in ECT's clinical outcomes. This article offers a comprehensive comparison of these trials while also exploring how patient characteristics, treatment protocols, and study designs may contribute to such pronounced outcome discrepancies. These differences highlight the heterogeneous nature of depression and underscore the need for personalized treatments. These studies also provide valuable insights into identifying the most suitable candidates for ketamine and ECT., (© The Author(s) 2023. Published by Oxford University Press on behalf of CINP.)

Objective: Electroconvulsive therapy (ECT) en bloc is defined as ECT administered on 2-3 consecutive days. In Denmark, ECT en bloc is recommended for severe conditions such as catatonia, treatment-resistant mania/psychosis, or imminent risk of suicide. To our knowledge, there are no recent reports on the use of ECT en bloc in clinical practice. Here, we provide such a report., Methods: We characterized the use of ECT en bloc in the period from 2006-2019 based on data from Danish national registers. Furthermore, we compared mortality rates between patients receiving ECT en bloc and patients receiving standard regimen ECT (not en bloc )., Results: We identified 2173 patients who received a total of 2734 ECT en bloc treatment courses in Denmark in the period from 2006 to 2019 (6% of the total number of ECT treatment courses). The use of ECT en bloc was stable over the study period (range: 138-196 patients per year). The most common treatment indications were unipolar depression (41%), psychotic disorder (23%), and bipolar disorder (20%). The vast majority (90%) received ECT en bloc voluntarily. The 1-year mortality rate ratio for ECT en bloc compared to standard regimen ECT was 1.42 (95%CI: 1.03-1.95)., Conclusion: The use of ECT en bloc in Denmark is stable both in terms of the number of patients treated and treatment indications. In keeping with ECT en bloc being used for severe conditions, those receiving this treatment have a higher mortality rate compared to those receiving standard ECT, warranting careful monitoring during follow-up.

Introduction: There have been important advances in the use of electroconvulsive therapy (ECT) to treat major depressive episodes. These include variations to the type of stimulus the brain regions stimulated, and the stimulus parameters (eg, stimulus duration/pulse width). Our aim is to investigate ECT types using a network meta-analysis (NMA) approach and report on comparative treatment efficacy, cognitive side effects and acceptability., Method: We will conduct a systematic review to identify randomised controlled trials that compared two or more ECT protocols to treat depression. This will be done using the following databases: Embase, MEDLINE PubMed, Web of Science, Scopus, PsycINFO, Cochrane CENTRAL and will be supplemented by personal contacts with researchers in the field. All authors will be contacted to provide missing information. Primary outcomes will be symptom severity on a validated continuous clinician-rated scale of depression, cognitive functioning measured using anterograde verbal recall, and acceptability calculated using all-cause drop-outs. Secondary outcomes will include response and remission rates, autobiographical memory following a course of ECT, and anterograde visuospatial recall.Bayesian random effects hierarchical models will compare ECT types. Additional meta-regressions may be conducted to determine the impact of effect modifiers and patient-specific prognostic factors if sufficient data are available., Discussion: This NMA will facilitate clinician decision making and allow more sophisticated selection of ECT type according to the balance of efficacy, cognitive side effects and acceptability., Ethics: This systematic review and NMA does not require research ethics approval as it will use published aggregate data and will not collect nor disclose individually identifiable participant data., Prospero Registration Number: CRD42022357098., Competing Interests: Competing interests: HAS serves as a scientific advisor to Cerebral Therapeutics, Holmusk Technologies, LivaNova, Neurolief, Neuronetics, Parow Entheobiosciences and SigmaStim (formerly MECTA Corporation); he receives honoraria and royalties from Elsevier and Oxford University Press; he is the inventor on non-remunerative US patents for Focal Electrically Administered Seizure Therapy (FEAST), titration in the current domain in ECT, and ECT devices with current adjustment, each held by SigmaStim; and he is the originator of magnetic seizure therapy. DoMM has received travel support from Miyuki Giken, speaker’s honorarium from Lundbeck and consultancy fees from Duncan Pharmaceuticals, all unrelated to the current work. DeMM, has received speaker's honoraria from MECTA and Otsuka and an honorarium from Janssen for participating in an esketamine advisory board meeting. All of these were unrelated to the current work. CHK, receives royalties from Cambridge University Press for Handbook of ECT, fees from UpToDate for ECT topics, and fees from Northwell Health for teaching in an ECT course. CL has received speaker's honoraria from MECTA, an honorarium from Janssen for participating in an esketamine advisory board meeting, and fees from Wesley Hospital and South Eastern Sydney Local Health District for teaching ECT courses. These were unrelated to the current work. The other authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The authors conducted a systematic review and meta-analysis of pharmacological interventions to diminish cognitive side effects of ECT., Methods: Electronic databases of Pubmed, PsycInfo, Embase and Scopus were searched from inception through 1 April, 2021, using terms for ECT (e.g. electroconvulsive therapy), cognitive outcome (e.g. cogni*) and pharmacological intervention (e.g. calcium channel blocker and general terms, like protein). Original studies with humans receiving ECT were included, which applied pharmacological interventions in comparison with placebo or no additive intervention to diminish cognitive side effects. Data quality was assessed using Risk of Bias and GRADE. Random-effects models were used. PROSPERO registration number was CRD42021212773., Results: Qualitative synthesis (systematic review) showed 52 studies reporting sixteen pharmacological intervention-types. Quantitative synthesis (meta-analysis) included 26 studies (1387 patients) describing twelve pharmacological intervention-types. Low-quality evidence of efficacy was established for memantine (large effect size) and liothyronine (medium effect size). Very low-quality evidence shows effect of acetylcholine inhibitors, piracetam and melatonin in some cognitive domains. Evidence of no efficacy was revealed for ketamine (very low-quality), herbal preparations with anti-inflammatory properties (very low to low-quality) and opioid receptor agonists (low-quality)., Conclusion: Memantine and liothyronine are promising for further research and future application. Quality of evidence was low because of differences in ECT techniques, study populations and cognitive measurements. These findings provide a guide for rational choices of potential pharmacological intervention research targets to decrease the burden of cognitive side effects of ECT. Future research should be more uniform in design and attempt to clarify pathophysiological mechanisms of cognitive side effects of ECT., (© 2022 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)