Electroconvulsive Therapy In Major Depressive Disorder Research Articles

Molecular mechanisms underlying structural plasticity of electroconvulsive therapy in major depressive disorder.

Although previous studies reported structural changes associated with electroconvulsive therapy (ECT) in major depressive disorder (MDD), the underlying molecular basis of ECT remains largely unknown. Here, we combined two independent structural MRI datasets of MDD patients receiving ECT and transcriptomic gene expression data from Allen Human Brain Atlas to reveal the molecular basis of ECT for MDD. We performed partial least square regression to explore whether/how gray matter volume (GMV) alterations were associated with gene expression level. Functional enrichment analysis was conducted using Metascape to explore ontological pathways of the associated genes. Finally, these genes were further assigned to seven cell types to determine which cell types contribute most to the structural changes in MDD patients after ECT. We found significantly increased GMV in bilateral hippocampus in MDD patients after ECT. Transcriptome-neuroimaging association analyses showed that expression levels of 726 genes were positively correlated with the increased GMV in MDD after ECT. These genes were mainly involved in synaptic signaling, calcium ion binding and cell-cell signaling, and mostly belonged to excitatory and inhibitory neurons. Moreover, we found that the MDD risk genes of CNR1, HTR1A, MAOA, PDE1A, and SST as well as ECT related genes of BDNF, DRD2, APOE, P2RX7, and TBC1D14 showed significantly positive associations with increased GMV. Overall, our findings provide biological and molecular mechanisms underlying structural plasticity induced by ECT in MDD and the identified genes may facilitate future therapy for MDD.

Posttraumatic stress disorder comorbidity in patients undergoing ECT for major depressive disorder.

Posttraumatic stress disorder (PTSD) is not recognized as an indication for electroconvulsive therapy (ECT). However, research indicates promise for this treatment modality. To elucidate the effects of ECT for treating PTSD, prospective research is needed. The first step in assessing the feasibility of such research is to determine if many patients being treated with ECT have comorbid PTSD. This study examined the PTSD comorbidity rates and compared demographic data among patients with major depressive disorder (MDD) who were treated with ECT vs patients with MDD who were not treated with ECT. Data from patients with MDD were obtained from the Nationwide Inpatient Sample. Approximately 10% of patients undergoing ECT for MDD also had PTSD. The difference in comorbidity of PTSD in those treated with ECT vs those not treated with ECT was approximately 1%. Prospective naturalistic studies that examine the response of PTSD to ECT are feasible because a sizable number of patients with PTSD are receiving ECT.

The effect of brain functional network following electroconvulsive therapy in major depressive disorder

PurposeThe purpose of this paper is to examine the changes of brain functional network after electroconvulsive therapy (ECT) treatment in major depressive disorder (MDD).Design/methodology/approachIn this study, resting electroencephalography (EEG) is used to explore the changes in spectral power density, functional connectivity and network topology elicited by an acute open-label course of ECT in a group of 19 MDD subjects. The brain functional network based on Pearson correlation is constructed in a continuous threshold space (0.38–0.59). Complex network theory is used to analyze the network characteristic such as the length of the characteristic path, clustering coefficient, degree, betweenness centrality, global efficiency and small-world architecture.FindingsThe results show that ECT increased the spectral power density of Delta, Theta and Alpha1 bands and the full frequency. ECT increases the functional connectivity in Delta and full frequency and reduces the functional connectivity in Alpha2 band. In the selected threshold space, the clustering coefficient, global efficiency and small-world attributes of the network are changed significantly after ECT.Originality/valueThe findings indicate that resting EEG could effectively characterize the changes of brain functional networks following ECT in MDD. The results provide a theoretical basis to explore the neurophysiological mechanism of ECT in the field of MDD treatment.

National Network of Depression Centers' Recommendations on Harmonizing Clinical Documentation of Electroconvulsive Therapy.

Electroconvulsive therapy (ECT) is a highly therapeutic and cost-effective treatment for severe and/or treatment-resistant major depression. However, because of the varied clinical practices, there is a great deal of heterogeneity in how ECT is delivered and documented. This represents both an opportunity to study how differences in implementation influence clinical outcomes and a challenge for carrying out coordinated quality improvement and research efforts across multiple ECT centers. The National Network of Depression Centers, a consortium of 26+ US academic medical centers of excellence providing care for patients with mood disorders, formed a task group with the goals of promoting best clinical practices for the delivery of ECT and to facilitate large-scale, multisite quality improvement and research to advance more effective and safe use of this treatment modality. The National Network of Depression Centers Task Group on ECT set out to define best practices for harmonizing the clinical documentation of ECT across treatment centers to promote clinical interoperability and facilitate a nationwide collaboration that would enable multisite quality improvement and longitudinal research in real-world settings. This article reports on the work of this effort. It focuses on the use of ECT for major depressive disorder, which accounts for the majority of ECT referrals in most countries. However, most of the recommendations on clinical documentation proposed herein will be applicable to the use of ECT for any of its indications.

The Effects of Ketamine on Cognition in Unipolar and Bipolar Depression: A Systematic Review.

Objective: To determine the objective neurocognitive effects of (1) single-dose ketamine, (2) repeated-dose ketamine, (3) ketamine adjunct to electroconvulsive therapy (ECT), and (4) ketamine as the anesthetic for ECT in major depressive disorder (MDD) and depression in bipolar disorder (BD).Data Sources: Cochrane, MEDLINE, Embase, and PsycINFO databases were searched on March 19, 2020 (updated July 2, 2020), using the terms terms major depressive disorderbipolar disorder and ketamine and their synonyms. Clinical trial registries (search date May 4, 2020) and reference sections of included articles were also searched. There was no restriction on language or year of publication.Study Selection: Of 4,035 identified articles, 17 met inclusion criteria. Controlled and open-label studies of adults who received at least 1 ketamine treatment for a current major depressive episode, as part of MDD or BD, were included. Only studies measuring cognition using at least 1 validated, objective neurocognitive assessment were eligible.Data Extraction: Results are presented using a narrative review format. Data regarding change in cognitive performance from baseline to end-of-treatment and/or differences in cognition between ketamine and control groups were extracted.Results: There were no negative effects of single- or repeated-dose intravenous ketamine up to 2 weeks post-treatment in MDD. Limited data were available for BD populations, as well as on other routes of ketamine administration.Conclusions: Data to definitively answer the question of whether ketamine has substantive or persistent cognitive effects are insufficient; thus, larger controlled trials measuring cognition as the primary outcome are needed. Future research should focus on different routes of ketamine administration, ketamine enantiomers, and BD populations.

The effect of anaesthetic dose on response and remission in electroconvulsive therapy for major depressive disorder: nationwide register-based cohort study.

Electroconvulsive therapy (ECT) is a safe and effective treatment for major depressive disorder (MDD). ECT treatment effect relies on induced generalised seizures. Most anaesthetics raise the seizure threshold and shorten seizure duration. There are no conclusive studies on the effect of anaesthetic dose on response and remission rates with ECT for MDD. We aimed to examine the effect of different dose intervals of anaesthetics on response and remission after ECT for MDD. We conducted a nationwide cohort study, using data from Swedish registers. Low-, medium- and high-dose intervals, adjusted for age and gender, were constructed for each anaesthetic drug. Response and remission were measured with the Clinical Global Impression - Severity and Improvement scales (CGI-I and CGI-S), and a self-rated version of the Montgomery-Åsberg Depression Rating Scale (MADRS-S). Logistic regression models were used to calculate adjusted odds ratios for response and remission rates. The study included 7917 patients who received ECT for MDD during 2012-2018. Patients were given either thiopental (64.1%) or propofol (35.9%). Low-dose intervals of anaesthetics were associated with increased rates of response (CGI-I: odds ratio 1.22, 95% CI 1.07-1.40, P = 0.004; MADRS-S: odds ratio 1.31, 95% CI 1.09-1.56, P = 0.004) and remission (CGI-S: odds ratio 1.37, 95% CI 1.17-1.60, P ≤ 0.001; MADRS-S: odds ratio 1.31, 95% CI 1.10-1.54, P = 0.002). We found improved treatment outcomes with low- compared with high-dose anaesthetic during ECT for MDD. To enhance treatment effect, deep anaesthesia during ECT for MDD should be avoided.

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

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...

ECT beyond unipolar major depression: systematic review and meta-analysis of electroconvulsive therapy in bipolar depression.

In this systematic review and meta-analysis, the response, remission, and speed of response in adults with major depressive disorder (MDD) and bipolar disorder in depressive episode (BDD) receiving an acute course of electroconvulsive therapy (ECT) were quantitatively analyzed. Using the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, 1660 citations were identified through five electronic databases. Nineteen articles met final inclusion criteria for meta-analysis. The pooled response and remission rates with ECT in MDD were 74.2% (n = 1246/1680) and 52.3% (n = 850/1626), respectively. In BDD, they were 77.1% (n = 437/567) and 52.3% (n = 275/377), respectively. Although response rates to ECT were statistically higher in BDD (OR = 0.73, 95% CI: 0.56-0.95, P = 0.02), remission rates were similar (OR = 0.91, 95% CI: 0.65-1.26, P = 0.56). Individuals with BDD vs. MDD required fewer number of ECT sessions to achieve response (SMD = -0.23, 95% CI: -0.44 to -0.023, P = 0.03). There were no significant moderator effects identified. Response rates and speed of response are higher in individuals with BDD; however, remission rates are equivalent. These findings support increased utilization of ECT in individuals with treatment-refractory BDD.

Effects of continuation electroconvulsive therapy on quality of life in elderly depressed patients: A randomized clinical trial

We examined whether electroconvulsive therapy (ECT) plus medications (“STABLE + PHARM” group) had superior HRQOL compared with medications alone (“PHARM” group) as continuation strategy after successful acute right unilateral ECT for major depressive disorder (MDD). We hypothesized that scores from the Medical Outcomes Study Short Form-36 (SF-36) would be higher during continuation treatment in the “STABLE + PHARM” group versus the “PHARM” group. The overall study design was called “Prolonging Remission in Depressed Elderly” (PRIDE). Remitters to the acute course of ECT were re-consented to enter a 6 month RCT of “STABLE + PHARM” versus “PHARM”. Measures of depressive symptoms and cognitive function were completed by blind raters; SF-36 measurements were patient self-report every 4 weeks.Participants were 120 patients >60 years old. Patients with dementia, schizophrenia, bipolar disorder, or substance abuse were excluded. The “PHARM” group received venlafaxine and lithium. The “STABLE + PHARM” received the same medications, plus 4 weekly outpatient ECT sessions, with additional ECT session as needed. Participants were mostly female (61.7%) with a mean age of 70.5 ± 7.2 years. “STABLE + PHARM” patients received 4.5 ± 2.5 ECT sessions during Phase 2. “STABLE + PHARM” group had 7 point advantage (3.5–10.4, 95% CI) for Physical Component Score of SF-36 (P < 0.0001), and 8.2 point advantage (4.2–12.2, 95% CI) for Mental Component Score (P < 0.0001). Additional ECT resulted in overall net health benefit. Consideration should be given to administration of additional ECT to prevent relapse during the continuation phase of treatment of MDD. Clinical Trials.govNCT01028508

Structural network changes in patients with major depression and schizophrenia treated with electroconvulsive therapy

Electroconvulsive therapy (ECT) is one of the most effective treatments in severe and treatment-resistant major depressive disorder (MDD). In schizophrenia (SZ), ECT is frequently considered in drug-resistant cases, as an augmentation of antipsychotic treatment or in cases when rapid symptom relief is indicated. Accumulating neuroimaging evidence suggests modulation of medial temporal lobe and prefrontal cortical regions in MDD by ECT. In SZ, ECT-effects on brain structure have not been systematically investigated so far. In this study, we investigated brain volume in 21 ECT-naïve patients (12 with MDD, 9 with SZ) who received right-sided unilateral ECT. Twenty-one healthy controls were included. Structural magnetic resonance imaging data were acquired before and after ECT. Healthy participants were scanned once. Source-based morphometry was used to investigate modulation of structural networks pre/post ECT. ECT had an impact on distinct structural networks in MDD and SZ. In both MDD and SZ SBM revealed a medial temporal lobe (MTL) network (including hippocampus and parahippocampal cortex) which showed a significant increase after ECT. The increase in MTL network strength was not associated with clinical improvement in either MDD or SZ. In SZ a lateral prefrontal/cingulate cortical network showed a volume increase after ECT, and this effect was accompanied by clinical improvement. These findings provide preliminary evidence for structural network change in response to ECT in MDD and SZ. The data suggest both diagnosis-specific and transdiagnostic ECT-effects on brain volume. In contrast to SZ, in MDD structural network modulation by ECT was not associated with clinical improvement.

Antidepressant Effects of Electroconvulsive Therapy Correlate With Subgenual Anterior Cingulate Activity and Connectivity in Depression

The mechanisms underlying the effects of electroconvulsive therapy (ECT) in major depressive disorder (MDD) are not fully understood. Resting-state functional magnetic resonance imaging (rs-fMRI) is a new tool to study the effects of brain stimulation interventions, particularly ECT. The authors aim to investigate the mechanisms of ECT in MDD by rs-fMRI.They used rs-fMRI to measure functional changes in the brain of first-episode, treatment-naive MDD patients (n = 23) immediately before and then following 8 ECT sessions (brief-pulse square-wave apparatus, bitemporal). They also computed voxel-wise amplitude of low-frequency fluctuation (ALFF) as a measure of regional brain activity and selected the left subgenual anterior cingulate cortex (sgACC) to evaluate functional connectivity between the sgACC and other brain regions.Increased regional brain activity measured by ALFF mainly in the left sgACC following ECT. Functional connectivity of the left sgACC increased in the ipsilateral parahippocampal gyrus, pregenual ACC, contralateral middle temporal pole, and orbitofrontal cortex. Importantly, reduction in depressive symptoms were negatively correlated with increased ALFF in the left sgACC and left hippocampus, and with distant functional connectivity between the left sgACC and contralateral middle temporal pole. That is, across subjects, as depression improved, regional brain activity in sgACC and its functional connectivity increased in the brain.Eight ECT sessions in MDD patients modulated activity in the sgACC and its networks. The antidepressant effects of ECT were negatively correlated with sgACC brain activity and connectivity. These findings suggest that sgACC-associated prefrontal-limbic structures are associated with the therapeutic effects of ECT in MDD.

What Does the Electroencephalogram Tell Us About the Mechanisms of Action of ECT in Major Depressive Disorders?

Electroconvulsive therapy (ECT) remains to be one of the most effective treatment options in treatment-resistant major depressive disorder (MDD). From the early days, researchers have embarked on extracting information from electroencephalography (EEG) recordings before, during, and after ECT to identify neurophysiological targets of ECT and discover EEG predictors of response to ECT in patients with MDD. In this article, we provide an overview of visually detected and quantitative EEG features that could help in furthering our understanding of the mechanisms of action of ECT in MDD. We further discuss the EEG findings in the context of postulated hypotheses of ECT therapeutic pathways. We introduce an alternative and unifying hypothesis suggesting that ECT may exert its therapeutic efficacy through resetting the aberrant functional connectivity and promoting the generation of new and healthy connections in brain regions implicated in MDD pathophysiology, a mechanism that may be in part mediated by the ECT-induced activation of inhibitory and neuroplasticity mechanisms. We further discuss the added value of EEG markers in the larger context of ECT research and as complementary to neuroimaging and genetic markers. We conclude by drawing attention to the need for longitudinal studies in large cohort of patients and the need for standardization and validation of EEG algorithms of functional connectivity across studies to facilitate the translation of EEG correlates of ECT response in routine clinical practice.

P 121. Systematic review of ECT in major depressive disorder and bipolar depression during pregnancy

Background Depression, as major depressive disorder (MDD) or as bipolar depression, is frequent among pregnant women (Evans et al., 2001) and an efficient treatment is fundamental. If left untreated, there are specific risks such as preterm delivery, low birth weight, and potentially death due to acute suicidality. Treatment of depression during pregnancy supposes a great challenge for pregnant women, their partner and for physicians involved. Despite psychopharmacotherapy and psychotherapy, electroconvulsive therapy (ECT) and other brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) or vagus nerve stimulation (VNS) are current available treatment strategies to treat depressive symptoms. ECT is recommended by the American Psychiatric Association Task Force on ECT as a safe and effective treatment of depression throughout pregnancy. However, ECT during pregnancy often involves concerns by both the patient and the physician due to unsolved questions regarding safety and tolerability as well as efficacy. Method In order to retrieve insights into the frequency of reports, safety and efficacy of ECT for the treatment of MDD and bipolar depression during pregnancy we performed a systematic review of the existing literature. All publications between 1942 and the 1th December 2012 in the Medline, Embase and Scopus databases, that deal with ECT in MDD and bipolar depression during pregnancy were considered. Results N=87 cases of ECT during pregnancy (MDD n =78; bipolar depression n =9) published in n =41 articles were detected. Of these 30 were case reports and 11 case series (with reported cases between n =2 and n =16). Furthermore, we evaluated the number of reported cases between the first report in 1942 and 2012 and divided the results in 4 time periods (1942–1959 n =46, 1960–1977 n =0, 1978–1995 n =14, and 1996–2012 n =18) in order to compare reported frequency. The results of our preliminary analysis suggest that ECT is efficacious and well tolerated in mother and offspring in the majority of analysed cases. In terms of safety, the comparison of the 4 time periods revealed that in the last analyzed time period a lower complication rate was observed. Most reported adverse effects were transient confusion, memory loss, headache and very rare premature contractions (mother) and fetal bradyarrhythmias. Further parameters (e.g. outcome of follow-up investigations, applied, narcotics, gestation age at the time of ECT, mean number of ECT sessions, detailed efficacy parameters as measured by psychometric scales, changes of the frequencies of reported ECTs during pregnancy) will be presented at the congress. Conclusions Considering the results of our systematic review, ECT seems feasible in pregnant patients with MDD or bipolar depression. Our data support ECT to be more safe in the last decades for mother and offspring; however, the registered reported frequency does not support an increasingly use of this method with regard to the mentioned indication.

Effectiveness and pattern of use of continuation and maintenance electroconvulsive therapy

Patients with major depressive disorder (MDD) who require an acute course of electroconvulsive therapy (ECT) have high relapse rates. Therefore, an effective maintenance treatment strategy needs to be established. Continuation and maintenance ECT (C/M-ECT) could be an adequate treatment option, although the lack of controlled studies has led to its usefulness being questioned. This review includes a detailed description of studies on the effectiveness/efficacy of ECT in MDD. Despite their methodological limitations, the results appear to support the idea that C/M-ECT would be a safe and effective alternative, especially in patients with severe and recurrent disease. Nevertheless, more controlled studies are needed to provide new evidence and allow a more accurate assessment of the efficacy, safety and pattern of use of C/M-ECT.

Eficacia y patrón de uso de la terapia electroconvulsiva de continuación y mantenimiento en el trastorno depresivo mayor

Patients with major depressive disorder (MDD) who require an acute course of electroconvulsive therapy (ECT) have high relapse rates. Therefore, an effective maintenance treatment strategy needs to be established. Continuation and maintenance ECT (C/M-ECT) could be an adequate treatment option, although the lack of controlled studies has led to its usefulness being questioned. This review includes a detailed description of studies on the effectiveness/efficacy of ECT in MDD. Despite their methodological limitations, the results appear to support the idea that C/M-ECT would be a safe and effective alternative, especially in patients with severe and recurrent disease. Nevertheless, more controlled studies are needed to provide new evidence and allow a more accurate assessment of the efficacy, safety and pattern of use of C/M-ECT.

Mask ventilation, hypocapnia, and seizure duration in electroconvulsive therapy

Study Objective To compare the Mapleson D circuit and the bag-valve-mask device for mask ventilation of patients undergoing electroconvulsive therapy (ECT). Design Cross-over study. Setting Single-center academic medical center. Patients 18 patients undergoing ECT for major depressive disorder. Interventions Patients were randomized to undergo mask ventilation by the Mapleson D circuit or the bag-valve-mask device. Measurements End-tidal CO 2, seizure duration, and airway pressure values were recorded. Main Results End-tidal CO 2 was significantly lower with the bag-valve-mask device. When compared with the bag-valve-mask device, ventilation with the Mapleson circuit resulted in rebreathing of CO 2 in nearly all patients, shorter expiratory time, and lower pressure ramp slope. Conclusions Hypocapnia was not associated with longer seizures, and the user-device interaction might affect device performance.

Antidepressant Medication Treatment Failure Does Not Predict Lower Remission With ECT for Major Depressive Disorder

To test whether antidepressant medication treatment failure predicts differential remission with electroconvulsive therapy (ECT) in nonpsychotic unipolar depression. Depressed patients diagnosed with the Structured Clinical Interview for DSM-IV receiving ECT were assessed for medication use with the Antidepressant Treatment History Form (ATHF) (N = 345). Response to ECT was assessed with the 24-item Hamilton Rating Scale for Depression. Baseline medication treatment failure was analyzed as a possible predictor of remission status. Dates of study enrollment were from May 1997 to July 2004. Resistance to antidepressant medication as assessed by the ATHF, either taken as a whole or for any individual class of medication, was not predictive of acute remission status with ECT. Treatment failure with anti-depressant medication does not predict acute remission status with ECT for nonpsychotically depressed patients.

Electroconvulsive Therapy After Repair of Cerebral Aneurysm

There are cases in the literature describing the use of electroconvulsive therapy (ECT) in patients with intracerebral aneurysms. We report the clinical course of a 60-year-old woman with a history of a recently ruptured intracerebral aneurysm and placement of a ventriculoperitoneal shunt that was successfully treated with ECT for major depressive disorder. Beta blockade with esmolol 20-50 mg was used to maintain her blood pressure, which ranged from 100/63 to 170/94 mm Hg. Propofol was used for anesthesia. There were no vascular complications secondary to the ECT procedure.

Successful ECT in a Patient With an Orbital Cavernous Hemangioma

There are no cases in the literature describing the use of electroconvulsive therapy (ECT) in a patient with an intraorbital vascular mass. We report the clinical course of a 69-year-old female with a cavernous hemangioma of the left orbit who was successfully treated with ECT for major depressive disorder. There were no apparent effects on the orbital hemangioma as a result of ECT-related blood pressure elevations measured up to 195/90 mm Hg despite pretreatment with intravenous esmolol. Modulation of ECT-related cardiovascular changes in the presence of intracranial or intraorbital vascular masses remains advisable to reduce the risk of an adverse vascular event during ECT. The use of propofol anesthesia appears to be preferable in such cases.