Vagus Nerve Stimulation as an Alternative to Maintenance Electroconvulsive Therapy for Difficult-to-Treat Depression.

ABSTRACT: Vagus nerve stimulation (VNS), an implantable neurostimulator, provides a valuable long-term treatment option for patients with difficult-to-treat depression. It has been reported that previous response to electroconvulsive therapy (ECT) might predict a better response to VNS and that VNS could reduce or eliminate the need for maintenance ECT in some patients. We present the case of a patient who received a total of more than 120 sessions of ECT over the course of 13 years because of a major depressive disorder, with favorable response but without achieving full remission. After implantation of VNS, ECT was discontinued, and her depressive symptoms improved, achieving remission within 12 months. This case supports VNS as an alternative to maintenance ECT in patients with difficult-to-treat depression who have shown previous response to ECT treatment.

Corticosteroids and mania: A systematic review.

OBJECTIVES: Corticosteroids are widely prescribed for a variety of medical conditions. Accumulating evidence suggests that their use may be associated with adverse psychiatric effects, including mania. In this systematic review, we aim to critically evaluate the existing literature on the association between corticosteroid use and the emergence of mania. METHODS: We conducted a comprehensive search of major electronic databases (PubMed, Embase, Cochrane Library) for relevant studies published up to the date of the search (12th January 2023). Inclusion criteria involve studies that investigate the association between corticosteroid use and the emergence of mania in adult patients. The primary outcome is the prevalence of (hypo)mania following corticosteroid administration. Secondary outcomes include potential risk factors, dose-response relationships, and differences among various corticosteroid formulations. RESULTS: The identified studies were subjected to a systematic selection process and data extraction by an independent reviewer. A total of 47 articles met the inclusion criteria for our systematic review. CONCLUSION: Our findings suggest that mania is a common side-effect of corticosteroid use, particularly in prednisone equivalent doses above 40 mg. These findings hold practical significance for clinicians and provide insights into potential interventions, including careful monitoring, dose adjustments, and consideration of psychotropic medications when managing corticosteroid-induced mania.

Electroconvulsive therapy related anxiety in patients with depression: The influence of cognitive coping styles.

INTRODUCTION: Electroconvulsive therapy (ECT) related anxiety (ERA) is a common phenomenon with high individual variability. The way patients cognitively cope with the prospects of receiving ECT could be a mechanism explaining individual differences in ERA. Cognitive coping like monitoring (information seeking, paying attention to consequences) and blunting (seeking distraction and reassurance) has been linked to anxiety in various medical settings, with monitoring leading to more and blunting to less anxiety. How cognitive coping is related to ERA, is unknown. METHODS: The sample consisted of 71 patients with unipolar or bipolar depression referred for ECT. Cognitive coping was assessed at baseline, while ERA was measured each morning before the ECT session. Using a Linear Mixed Model, the influence of cognitive coping styles on ERA was investigated. RESULTS: Blunting was associated with lower levels of ERA (p = 0.037) and monitoring tended to be associated with higher levels of ERA (p = 0.057) throughout the ECT course. Patients with a depression with psychotic features scored significantly higher on monitoring, but even after controlling for monitoring they showed a stronger decline in ERA during treatment compared to patients without psychotic features. CONCLUSION: Cognitive coping style contributes to individual differences in ERA. Blunting is a protective factor, leading to lower levels of ERA throughout the ECT course. On the contrary, patients with a higher monitoring style tend to experience higher levels of ERA. Further insights in these coping mechanisms may help to tailor future treatment to individual patients and reduce ERA before and during ECT treatment.

Ketamine or ECT? What Have We Learned From the KetECT and ELEKT-D Trials?

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.

Electroconvulsive therapy improves somatic symptoms before mood in patients with depression: A directed network analysis.

BACKGROUND: The recent network perspective of depression conceptualizes depression as a dynamic network of causally related symptoms, that contrasts with the traditional view of depression as a discrete latent entity that causes all symptoms. Electroconvulsive therapy (ECT) is an effective treatment for severe depression, but little is known about the temporal trajectories of symptom improvement during a course of ECT. OBJECTIVE: To gain insight into the dynamics of depressive symptoms in individuals treated with ECT. METHODS: The Quick Inventory of Depressive Symptomatology (QIDS) was used to assess symptoms twice a week in 68 participants with a unipolar or bipolar depression treated with ECT, with an average of 12 assessments per participant. Dynamic time warping (DTW) was used to analyze individual time series data, which were subsequently aggregated to calculate a directed symptom network and the in- and out-strength for each symptom. RESULTS: Participants had a mean age of 49.6 (SD = 12.8) and 60% were female. Somatic symptoms (e.g., decreased weight) and suicidal ideation showed the highest out-strength values, indicating that their improvement tended to precede improvements in mood symptoms, which showed high in-strength. Sad mood had the highest in-strength, and thus appeared to be the last symptom to improve during ECT treatment (p < 0.001). CONCLUSION: This study addresses a gap in the existing literature on ECT, by first analysing the temporal trajectories of symptoms within individual patients and subsequently aggregating them to the group level. The results show that somatic symptoms tend to improve before mood symptoms during ECT.

The Cortisol Awakening Response as a Biomarker for Cognitive Side-Effects of Electroconvulsive Therapy.

OBJECTIVE: To test whether the cortisol awakening response (CAR) could be a biomarker for cognitive decline during electroconvulsive therapy (ECT). METHODS: We studied 50 older patients with depression who were treated with ECT from the MODECT cohort. We used linear regression analyses to examine the association between CAR and cognitive change, assessed by the change in Mini Mental State Examination scores between baseline and 1 week after ECT course. CAR was assessed by the area under the curve of cortisol levels, according to Pruessner's-formula. Associations were adjusted for putative confounders, based on previous literature and availability. RESULTS: We found no significant associations between the CAR and cognitive change during the ECT course in (un)adjusted models. CONCLUSION: Our results indicate that the CAR is not usable as a biomarker for ECT-induced cognitive decline during ECT course. Further research in cohorts with larger samples is needed.

Effective resting-state connectivity in severe unipolar depression before and after electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depressive disorders. A recent multi-center study found no consistent changes in correlation-based (undirected) resting-state connectivity after ECT. Effective (directed) connectivity may provide more insight into the working mechanism of ECT. OBJECTIVE: We investigated whether there are consistent changes in effective resting-state connectivity. METHODS: This multi-center study included data from 189 patients suffering from severe unipolar depression and 59 healthy control participants. Longitudinal data were available for 81 patients and 24 healthy controls. We used dynamic causal modeling for resting-state functional magnetic resonance imaging to determine effective connectivity in the default mode, salience and central executive networks before and after a course of ECT. Bayesian general linear models were used to examine differences in baseline and longitudinal effective connectivity effects associated with ECT and its effectiveness. RESULTS: Compared to controls, depressed patients showed many differences in effective connectivity at baseline, which varied according to the presence of psychotic features and later treatment outcome. Additionally, effective connectivity changed after ECT, which was related to ECT effectiveness. Notably, treatment effectiveness was associated with decreasing and increasing effective connectivity from the posterior default mode network to the left and right insula, respectively. No effects were found using correlation-based (undirected) connectivity. CONCLUSIONS: A beneficial response to ECT may depend on how brain regions influence each other in networks important for emotion and cognition. These findings further elucidate the working mechanisms of ECT and may provide directions for future non-invasive brain stimulation research.

Reviewing the neurobiology of electroconvulsive therapy on a micro- meso- and macro-level.

BACKGROUND: Electroconvulsive therapy (ECT) remains the one of the most effective of biological antidepressant interventions. However, the exact neurobiological mechanisms underlying the efficacy of ECT remain unclear. A gap in the literature is the lack of multimodal research that attempts to integrate findings at different biological levels of analysis METHODS: We searched the PubMed database for relevant studies. We review biological studies of ECT in depression on a micro- (molecular), meso- (structural) and macro- (network) level. RESULTS: ECT impacts both peripheral and central inflammatory processes, triggers neuroplastic mechanisms and modulates large scale neural network connectivity. CONCLUSIONS: Integrating this vast body of existing evidence, we are tempted to speculate that ECT may have neuroplastic effects resulting in the modulation of connectivity between and among specific large-scale networks that are altered in depression. These effects could be mediated by the immunomodulatory properties of the treatment. A better understanding of the complex interactions between the micro-, meso- and macro- level might further specify the mechanisms of action of ECT.

Knowledge and Attitudes of First- and Final-Year Medical Students about Electroconvulsive Therapy: The Impact of Media.

OBJECTIVE: The aim of this study is to evaluate medical students' knowledge about and attitudes towards electroconvulsive therapy (ECT) and to assess the impact of information sources (including those within and outside the curriculum) on knowledge and attitudes by comparing first- and final-year medical students. METHODS: Two hundred and ninety-five first-year and one hundred forty-nine final-year medical students of the University of Leuven (KU Leuven) in Belgium responded to an anonymous self-administered survey which consisted of questions about sociodemographic background, self-perceived knowledge about medicine, psychiatry and ECT, interest in psychiatry, experience with psychiatric disorders, information sources of ECT, and knowledge about and attitudes towards ECT. RESULTS: Compared to first-year medical students, final-year students had better knowledge about and more positive attitudes towards ECT, partially explained by differences in information sources. Nevertheless, both student groups showed an average knowledge score below 50%. Whereas freshmen attributed their knowledge to movies or documentaries, senior students gained knowledge mainly at university courses, scientific journals, and attending live ECT sessions. A significant positive correlation was found between knowledge about and positive attitudes towards ECT. CONCLUSIONS: The knowledge of first- and final-year medical students remains limited, potentially due to limited instruction about ECT in medical courses. The use of media as an information source predicted negative attitudes towards ECT. Therefore, the stigma and misinformation provided in the media need to be addressed in the medical curriculum.

Borderline Personality Disorder and Outcome of Electroconvulsive Therapy in Patients With Depression: A Systematic Review.

ABSTRACT: Major depressive disorder (MDD) commonly coincides with borderline personality disorder (BPD), aggravating depressive symptom severity and reducing the odds of responding to antidepressant treatments. In this systematic review, we summarize the available evidence assessing the question whether the presence of BPD reduces the response to electroconvulsive therapy (ECT) in individuals with MDD.We conducted a systematic literature search (up to December 2021) without language restriction, using the PubMed/MEDLINE, Web of Science (Core Collection), Embase, and Cochrane Library databases, for prospective and retrospective studies, which assessed the efficacy of ECT in patients with MDD and comorbid BPD.Of the 2548 records screened, 6 articles were selected, 2 of which were based on the same population, leading to 5 included articles. The included studies are reporting on 3465 patients with MDD, of which 1206 had a comorbid BPD. Five of the 6 studies found a less robust response to ECT in patients with MDD and BPD compared with those without BPD.Our results suggest that, in patients with MDD, the presence of BPD is associated with a less robust acute response to ECT. Patients with BPD, however, showed a significant response to ECT in all of the included studies. More longitudinal studies with higher accuracy in BPD diagnosis are needed. Although a comorbid BPD seems to decrease the efficacy of ECT for MDD, ECT remains an effective treatment option in this severely ill patient group.

Asystole During Electroconvulsive Therapy: Does Electrode Placement Matter? A Systematic Review.

ABSTRACT: Asystole presenting at the start of electrical stimulus application during electroconvulsive therapy (ECT) is a relatively common occurrence. It is most likely caused by vagal nerve stimulation, affecting autonomic cardiac tone. This article reviews the effect of the electrode placement (EP) on the incidence and severity of bradycardia and asystole. A systematic literature review was conducted using the Embase and PubMed databases, up to September 2021, searching for studies evaluating the effect of EP on bradycardia and/or asystole during ECT. Nine case reports describing asystole in patients receiving ECT almost exclusively reported the association with bitemporal (BT) EP. One small descriptive study found no significant effect of EP on cardiac pauses. The results from 4 cohort studies, however, suggest that a right unilateral placement bears a higher risk for developing bradycardia and asystole than BT and bifrontal ECT. The available evidence suggests that right unilateral ECT holds a greater risk for the development of bradycardia and asystole than BT and bifrontal EP.

Lateralized Raise in Intraocular Pressure During Electroconvulsive Therapy: A Tonometry Pilot Study.

The aim of this study was to evaluate intraocular pressure (IOP) changes during and after electroconvulsive therapy. In 20 patients, IOP was measured using a handheld iCare tonometer before, during, and up to 15 minutes after the seizure. Electrode placement was either right unilateral (RUL) or bilateral (BL). Statistical analyses were done at baseline, during, and 15 minutes after the seizure. In the RUL group (n = 14), the IOP in the left eye increased from 14.8 mm Hg before the seizure to 27.8 mm Hg during the seizure ( P = 0.0001) and decreased to 14.0 mm Hg after the seizure ( P = 0.0002). The IOP in the right eye increased from 15.4 mm Hg before the seizure to 34.4 mm Hg during the seizure ( P = 0.0001) and decreased to 16.0 mm Hg after the seizure ( P = 0.0002). In the BL group (n = 6), the IOP in the left eye increased from 13.0 mm Hg before the seizure to 26.3 mm Hg during the seizure ( P = 0.1250) and decreased to 14.5 mm Hg after the seizure ( P = 0.250). In the right eye, the IOP increased from 13.3 mm Hg before the seizure to 28.4 mm Hg during the seizure ( P = 0.1250) and decreased to 13.7 mm Hg after the seizure ( P = 0.25). When the results were compared between the 2 electrode placements, the difference in IOP between the right and left eye was higher in the RUL group during (RUL 6.7 mm Hg vs BL 2.0 mm Hg, P = 0.0231) and after (RUL 2.1 mm Hg vs BL −0.8 mm Hg, P = 0.0492) the seizure. RUL stimulation with electroconvulsive therapy causes a rise in IOP that is partially lateralized, ipsilateral to the side of stimulation.

Comparative efficacy, cognitive effects and acceptability of electroconvulsive therapies for the treatment of depression: protocol for a systematic review and network meta-analysis.

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.

White matter changes following electroconvulsive therapy for depression: a multicenter ComBat harmonization approach.

ECT is proposed to exert a therapeutic effect on WM microstructure, but the limited power of previous studies made it difficult to highlight consistent patterns of change in diffusion metrics. We initiated a multicenter analysis and sought to address whether changes in WM microstructure occur following ECT. Diffusion tensor imaging (DTI) data (n = 58) from 4 different sites were harmonized before pooling them by using ComBat, a batch-effect correction tool that removes inter-site technical variability, preserves inter-site biological variability, and maximizes statistical power. Downstream statistical analyses aimed to quantify changes in Fractional Anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD) and Axial Diffusivity (AD), by employing whole-brain, tract-based spatial statistics (TBSS). ECT increased FA in the right splenium of the corpus callosum and the left cortico-spinal tract. AD in the left superior longitudinal fasciculus and the right inferior fronto-occipital fasciculus was raised. Increases in MD and RD could be observed in overlapping white matter structures of both hemispheres. At baseline, responders showed significantly smaller FA values in the left forceps major and smaller AD values in the right uncinate fasciculus compared with non-responders. By harmonizing multicenter data, we demonstrate that ECT modulates altered WM microstructure in important brain circuits that are implicated in the pathophysiology of depression. Furthermore, responders appear to present a more decreased WM integrity at baseline which could point toward a specific subtype of patients, characterized by a more altered neuroplasticity, who are especially sensitive to the potent neuroplastic effects of ECT.

ECT-related anxiety during maintenance ECT: A prospective study.

OBJECTIVE: Despite the established safety of electroconvulsive therapy (ECT), ECT-related anxiety (ERA) remains one of the most distressing complications of ECT. ERA is reported to diminish during an acute course of ECT, but it was never studied during maintenance ECT (M-ECT). Our aim was to study the trajectories of ERA during M-ECT and how they differ from trajectories during the acute course. METHODS: Thirty-nine patients with unipolar or bipolar depression, retained for M-ECT after an acute ECT course, were included. ERA was assessed the morning before each ECT session using the ECT-related Anxiety Questionnaire (ERAQ). RESULTS: ERA remained stable during M-ECT (RC = -0.05 (SE = 0.06), t(8.35) = -0.86, p = 0.42), while ERA declined significantly during the acute course (RC = -0.85 (SE = 0.30), t(33.6) = -2.81, p = 0.0082). During the acute course, patients with a psychotic depression were more anxious at baseline (t(32)= -2.42, p = 0.02), and showed a significant decline in ERAQ scores (RC = -1.65 (SE = 0.46), t(31.6) = -3.56, p = 0.0012), whereas patients with a non-psychotic depression were less anxious at baseline and retained stable ERAQ scores during the acute course (RC = -0.06 (SE = 0.41), t(32.1) = -0.14, p = 0.89). Whereas a correlation (r = 0.48) was noticed between the decline of depression severity and ERA during the acute course, this was not the case during M-ECT. CONCLUSION: ERA runs a stable course during M-ECT, after having decreased during the acute course. During the acute course, ERA trajectories differed significantly between patients with a psychotic and non-psychotic depression. Decline of depression severity and ERA are significantly connected during the acute course of ECT. Both depression severity and ERA remain stable during M-ECT.

Effectiveness of electroconvulsive therapy in patients lacking decision making capacity: A systematic review and meta-analysis.

BACKGROUND: Electroconvulsive therapy (ECT) is provided for patients with severe and often life-threatening illness, who lack decision making capacity to consent to treatment (DMC-T) in clinical settings. OBJECTIVE: The aim of this study is to summarize previous studies investigating clinical outcomes of ECT in patients lacking DMC-T. METHODS: A systematic review and meta-analysis of studies reporting clinical outcomes of ECT in patients lacking DMC-T with any psychiatric diagnoses was conducted. The primary outcome was clinical improvement. Secondary outcomes were cognitive outcomes and six month readmission rate. Hedges' g and odds ratios were calculated using a random-effects model. The protocol was registered in Open Science Framework (https://osf.io/rxjkm). RESULTS: Of 3552 identified articles, 41 studies (n = 1299) were included. Approximately 80% of patients lacking DMC-T responded to ECT, and part of the patients regained capacity to consent and consented to further treatment with ECT. A total of seven studies (n = 1081) were included for meta-analysis. Patients without DMC-T showed superior clinical improvement and less cognitive side effects compared with those with DMC-T, whereas the groups did not show any difference in readmission rate. Several clinical characteristics at baseline and ECT techniques were significantly different between the groups. CONCLUSION: ECT is equally, if not superiorly, effective in patients lacking DMC-T compared to patients with DMC-T. ECT can potentially enhance patients' autonomy, without increasing the risk of cognitive side effects. These results support the clinical and ethical legitimacy of ECT provision for patients with the most severe illness who lack DMC-T at start of treatment.

Rivastigmine for ECT-induced cognitive adverse effects in late life depression (RECALL study): A multicenter, randomized, double blind, placebo-controlled, cross-over trial in patients with depression aged 55 years or older: Rationale, objectives and methods.

Background: Cognitive side-effects are an important reason for the limited use of electroconvulsive therapy (ECT). Cognitive side-effects are heterogeneous and occur frequently in older persons. To date, insight into these side-effects is hampered due to inconsistencies in study designs and small sample sizes. Among all cognitive side-effects, confusion and delirious states are especially troublesome for patients, relatives and clinicians. In particular inter-ictal delirium-like states are worrisome, since they may lead to premature treatment discontinuation. Besides a need for further insight into determinants of cognitive side-effects of ECT, there is a great need for treatment options. Methods and design: The Rivastigmine for ECT-induced Cognitive Adverse effects in Late Life depression (RECALL) study combines a multicenter, prospective cohort study on older patients with depression, treated with ECT, with an embedded randomized, placebo-controlled cross-over trial to examine the effect of rivastigmine on inter-ictal delirium. Patients are recruited in four centers across the Netherlands and Belgium. We aim to include 150 patients into the cohort study, in order to be able to subsequently include 30 patients into the trial. Patients are included in the trial when inter-ictal delirium, assessed by the Confusion Assessment method (CAM), or a drop in Mini Mental State Examination (MMSE) score of ≥4 during ECT, develops. In the cohort study, comprehensive measurements of ECT-related cognitive side-effects-and their putative determinants-are done at baseline and during the ECT-course. The primary outcome of the clinical trial is the effectiveness of rivastigmine on inter-ictal delirium-severity, assessed with a change in the Delirium Rating Scale-Revised-98. Secondary outcomes of the clinical trial are several ECT-characteristics and side-effects of rivastigmine. Discussion: This study is the first clinical trial with a focus on ECT-induced, inter-ictal delirium. The cohort provides the basis for recruitment of patients for the cross-over trial and additionally provides an excellent opportunity to unravel cognitive side-effects of ECT and identify putative determinants. This paper describes the rationale and study protocol. Clinical trial registration: EudraCT 2014-003385-24.