Electroconvulsive Therapy In Treatment-resistant Depression Research Articles

Efficacy and safety of esketamine versus propofol in electroconvulsive therapy for treatment-resistant depression: A randomized, double-blind, controlled, non-inferiority trial

BackgroundElectroconvulsive therapy (ECT) is a commonly used alternative for treatment-resistant depression (TRD). Although esketamine has a rapid pharmacological antidepressant action, it has not been studied as an ECT anesthetic. The objective of this study was to compare the efficacy and safety of esketamine with propofol when both are used as ECT anesthetic agents. MethodsForty patients with TRD were assigned to one of two arms in a double-blind, randomized controlled trial: esketamine or propofol anesthesia for a series of eight ECT sessions. Using a non-inferiority design, the primary outcome was the reduction in HAMD-17 depressive symptoms. The other outcomes were: rates of response and remission, anxiety, suicidal ideation, cognitive function, and adverse events. These were compared in an intention-to-treat analysis. ResultsEsketamine-ECT was non-inferior to propofol-ECT for reducing TRD symptoms after 8 sessions (adjusted Δ = 2.0, 95 % CI: −1.2–5.1). Compared to propofol-ECT, esketamine-ECT also had higher depression response (80 % vs. 70 %; p = .06) and remission (65 % vs. 55 %; p = .11) rates but non-inferiority was not established. In four components of cognitive function (speed of processing, working memory, visual learning, and verbal learning) esketamine-ECT was non-inferior to propofol-ECT. The results for anxiety, suicidal ideation, and adverse events (all p's > .05) were inconclusive. ConclusionEsketamine was non-inferior to propofol when both are used as anesthetics for TRD patients undergoing ECT. Replication studies with larger samples are needed to examine the inconclusive results. Registration numberChiCTR2000033715.

Efficacy and Controversies Surrounding Electroconvulsive Therapy for Treatment-Resistant Depression: A Literature Review

Electroconvulsive therapy (ECT) remains a vital treatment option for individuals with treatment-resistant depression (TRD). Despite its historical stigma, controversy, and limited accessibility, ECT has been demonstrated to be beneficial and effective in severe cases of depressive disorders, where medication fails to produce results. It has been utilized since 1938 as a therapeutic technique for various psychiatric disorders, often used as an alternative to chemically induced seizures. The public’s perspectives on ECT hold significance as they can shape attitudes toward patients undergoing this therapy and the discrimination associated with receiving ECT. Additionally, the perspectives of patients who may benefit from ECT and those who are already undergoing treatment are crucial as they can influence treatment decisions and consent processes. This literature review examines the efficacy and controversies surrounding ECT in the management of TRD. Studies assessing the effectiveness of ECT in TRD, along with associated adverse effects and ethical considerations, are reviewed. Additionally, the role of ECT in contemporary psychiatric practice and its comparison with alternative treatments for TRD are discussed. The review highlights the complex interplay between clinical efficacy, safety, patient preferences, and societal perceptions in shaping the utilization of ECT in the treatment of TRD.

Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression

The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD. To evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT. This secondary analysis of an open-label noninferiority randomized clinical trial was a multicenter study conducted at 5 US academic medical centers from April 7, 2017, to November 11, 2022. Analyses for this study, which were not prespecified in the trial protocol, were conducted from May 10 to Oct 31, 2023. The study cohort included patients with TRD, aged 21 to 75 years, who were in a current nonpsychotic depressive episode of at least moderate severity and were referred for ECT by their clinicians. Eligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks. Association between baseline factors (including 16-item Quick Inventory of Depressive Symptomatology Self-Report [QIDS-SR16], Montgomery-Asberg Depression Rating Scale [MADRS], premorbid intelligence, cognitive function, history of attempted suicide, and inpatient vs outpatient status) and treatment response were assessed with repeated measures mixed-effects model analyses. Among the 365 participants included in this study (mean [SD] age, 46.0 [14.5] years; 191 [52.3%] female), 195 were randomized to the ketamine group and 170 to the ECT group. In repeated measures mixed-effects models using depression levels over 3 weeks and after false discovery rate adjustment, participants with a baseline QIDS-SR16 score of 20 or less (-7.7 vs -5.6 points) and those starting treatment as outpatients (-8.4 vs -6.2 points) reported greater reduction in the QIDS-SR16 with ketamine vs ECT. Conversely, those with a baseline QIDS-SR16 score of more than 20 (ie, very severe depression) and starting treatment as inpatients reported greater reduction in the QIDS-SR16 earlier in course of treatment (-8.4 vs -6.7 points) with ECT, but scores were similar in both groups at the end-of-treatment visit (-9.0 vs -9.9 points). In the ECT group only, participants with higher scores on measures of premorbid intelligence (-14.0 vs -11.2 points) and with a comorbid posttraumatic stress disorder diagnosis (-16.6 vs -12.0 points) reported greater reduction in the MADRS score. Those with impaired memory recall had greater reduction in MADRS during the second week of treatment (-13.4 vs -9.6 points), but the levels of MADRS were similar to those with unimpaired recall at the end-of-treatment visit (-14.3 vs -12.2 points). Other results were not significant after false discovery rate adjustment. In this secondary analysis of the ELEKT-D randomized clinical trial of ECT vs ketamine, greater improvement in depression was observed with intravenous ketamine among outpatients with nonpsychotic TRD who had moderately severe or severe depression, suggesting that these patients may consider ketamine over ECT for TRD.

The Impact of Ketamine-Based Versus Non-Ketamine-Based ECT Anesthesia Regimens on the Severity of Patients’ Depression and Occurrence of Adverse Events: A Systematic Review with Meta-Analysis

Objective: To compare efficacy and safety outcomes for ketamine anesthesia + electroconvulsive therapy (ECT) versus nonketamine anesthesia + ECT in treatment-resistant depression (TRD) patients. Data Sources: PubMed and Embase were searched from the earliest date through November 27, 2023. Study Selection and Data Extraction: Relevant randomized controlled trials (RCTs) of ketamine + ECT versus nonketamine anesthesia + ECT that reported data on remission (odds ratio [OR]), defined as a Hamilton Depression Rating Scale (HAM-D) and Montgomery-Asburg Depression Rating Scale (MADRS) score <8-10) and mean differences (MDs) in HAM-D scores after several ECT sessions were compared using inverse variance methods. The risk of bias (RoB) was assessed using the Cochrane RoB tool. Data Synthesis: Seventeen RCTs (RoB: Low N = 12, Moderate N = 2, High N = 3) with 1181 total patients met inclusion criteria. Patients receiving ECT experienced greater clinical remission (OR: 1.78, [95% confidence interval (CI): 1.08-2.93], I2 = 11%, N = 9) and lower HAM-D scores after the third through sixth ECT sessions as well as the eighth ECT session when ketamine versus nonketamine anesthesia was used. Ketamine use with ECT significantly increased fear with hallucinations (OR: 1.99, [95% CI: 1.11-3.58], I2 = 0%, N = 7) than with nonketamine anesthesia. Relevance to Patient Care and Clinical Practice: Selecting ketamine-based anesthesia could more quickly and profoundly enhance the beneficial effects of ECT for patients with severe TRD, but the balance of benefits to harm is unclear as there may be additional adverse events. Conclusion: Ketamine is a promising anesthesia adjunct to ECT that may enhance antidepressant effects in exchange for more adverse events.

Vagus nerve stimulation allows to cease maintenance electroconvulsive therapy in treatment-resistant depression: a retrospective monocentric case series.

The use of vagus nerve stimulation (VNS) to reduce or stop electroconvulsive therapy (ECT) in treatment-resistant depression seems promising. The aim of this study was to investigate the efficacy of VNS on the reduction of ECT sessions and mood stabilization. We conducted a monocentric retrospective case series of patients who suffered from treatment-resistant depression, treated with ECT and referred to our center for VNS. We investigated the number and the frequency of ECT sessions before and after VNS implantation. Secondary criteria consisted in the Montgomery Åsberg Depression Rating Scale (MADRS) score, number of medical treatments, dosage of the main treatment and length of hospital stays before and after VNS. Additionally, we sent an anonymous survey to psychiatrists and other physicians in our institution to investigate their knowledge and perception of VNS therapy to treat treatment-resistant depression. Seven patients benefited from VNS: six (86%) were female (mean age of 51.7 +/- 16.0 years at surgery), and five (71%) suffered from bipolar depression (three type I and two type II). All patients were followed up at least 2 years post-implantation (range: 27-68 months). Prior to VNS, six patients were treated by maintenance ECT. After VNS, three (43%) patients did not require maintenance ECT anymore, and three (43%) patients required less frequent ECT session with a mean 14.7 +/- 9.8 weeks between sessions after VNS vs. 2.9 +/- 0.8 weeks before VNS. At last follow-up, 4 (57%) patients had stopped ECT. Five (71%) patients implanted with VNS were good responders (50% decrease relative to baseline MADRS). According to the survey, psychiatrists had a significantly better perception and knowledge of ECT, but a worse perception and knowledge of VNS compared to other physicians. VNS is a good option for treatment-resistant depression requiring maintenance ECT dependence. Larger on-going studies will help broaden the implanted patients while strengthening psychiatrists' knowledge on this therapy.

Magnetic Waves vs. Electric Shocks: A Non-Inferiority Study of Magnetic Seizure Therapy and Electroconvulsive Therapy in Treatment-Resistant Depression.

Treatment-resistant depression (TRD), characterized by the failure to achieve symptomatic remission despite multiple pharmacotherapeutic treatments, poses a significant challenge for clinicians. Electroconvulsive therapy (ECT) is an effective but limited option due to its cognitive side effects. In this context, magnetic seizure therapy (MST) has emerged as a promising alternative, offering comparable antidepressant efficacy with better cognitive outcomes. However, the clinical outcomes and cognitive effects of MST require further investigation. This double-blinded, randomized, non-inferiority study aims to compare the efficacy, tolerability, cognitive adverse effects, and neurophysiological biomarkers of MST with bilateral ECT (BT ECT) in patients with TRD. This study will employ multimodal nuclear magnetic resonance imaging (MRI) and serum neurotrophic markers to gain insight into the neurobiological basis of seizure therapy. Additionally, neurophysiological biomarkers will be evaluated as secondary outcomes to predict the antidepressant and cognitive effects of both techniques. The study design, recruitment methods, ethical considerations, eligibility criteria, interventions, and blinding procedures are described. The expected outcomes will advance the field by offering a potential alternative to ECT with improved cognitive outcomes and a better understanding of the underlying pathophysiology of depression and antidepressant therapies.

Response to electroconvulsive therapy in treatment-resistant depression: nationwide observational follow-up study.

Previous studies have not investigated response rates after electroconvulsive therapy (ECT) in patients with non-psychotic treatment-resistant depression (TRD). To assess and compare the response rate of ECT for patients with TRD and non-TRD, in a large and clinically representative patient sample. Patients aged ≥18 years, who were treated for a unipolar, non-psychotic depressive episode with at least one ECT session as part of a first-time, index ECT series between 1 January 2011 and 31 December 2017 were included from the Swedish National Quality Register for ECT. Patients who had initiated a third consecutive trial of antidepressants or add-on medications before start of ECT were classified as having TRD. Patients not meeting criteria for TRD were classified as non-TRD. The main outcome was response to ECT according to the Clinical Global Impressions - Improvement Scale (CGI-I), scored as 1 or 2 ('very much' or 'much improved' after ECT, respectively). Logistic regression was used to compare outcome measures between TRD and non-TRD, adjusting for potential confounders. A total of 4244 patients were included. Of these, 1121 patients had TRD and 3123 patients had non-TRD. The CGI-I response rate was 65.9% in the TRD group compared with 75.9% in the non-TRD group (adjusted odds ratio 0.64, 95% CI 0.54-0.75). Older age and more severe depression were predictors of response in patients with TRD. A clear majority of patients with TRD, as well as patients with non-TRD, responded to ECT, although the response rate was somewhat lower for TRD.

Electroconvulsive therapy for treatment-resistant depression.

Electroconvulsive therapy (ECT), the oldest brain stimulation procedure in psychiatry, is associated with rapid response and remission in majority of patients with resistant, severe, and sometimes life-threatening depression. ECT has been included as an essential component in the definition of treatment-resistant depression (TRD) to display the course and diversification of TRD. On the other hand, ECT remains the treatment of choice for the most severe incapacitating forms of TRD and is a cost-effective treatment. In this chapter, we reviewed some essential studies, meta-analysis, and expert guidelines regarding ECT in TRD. ECT should not be considered as a treatment of last resort, and its administration should be considered on the basis of individual patient and illness factors. The clinical role of ECT vs other neurostimulation treatments for TRD, that is, repetitive transcranial magnetic stimulation, were also explored. Much effort has been directed toward the clinical and basic research about mechanisms of action of ECT in depression. A thorough understanding of the neurobiological effects of ECT may increase our understanding of its therapeutic effects, ultimately leading to improved patient care. We also showed that the distinct mechanisms of ECT in biological treatments of major depressive disorder (MDD) and some recent approaches to understand this most common psychiatric disorder. ECT should remain a standard part of modern psychiatric medicine. We recommend a more careful and thoughtful application of this traditional but effective technology.

Longitudinal trajectory of response to electroconvulsive therapy associated with transient immune response & white matter alteration post-stimulation.

Research suggests electroconvulsive therapy (ECT) induces an acute neuroinflammatory response and changes in white matter (WM) structural connectivity. However, whether these processes are related, either to each other or to eventual treatment outcomes, has yet to be determined. We examined the relationship between levels of peripheral pro-inflammatory cytokines and diffusion imaging-indexed changes in WM microstructure in individuals with treatment-resistant depression (TRD) who underwent ECT. Forty-two patients were assessed at baseline, after their second ECT (T2), and after completion of ECT (T3). A Montgomery Åsberg Depression Rating Scale improvement of >50% post-ECT defined ECT-responders (n = 19) from non-responders (n = 23). Thirty-four controls were also examined. Tissue-specific fractional anisotropy (FAt) was estimated using diffusion imaging data and the Free-Water method in 17 WM tracts. Inflammatory panels were evaluated from peripheral blood. Cytokines were examined to characterize the association between potential ECT-induced changes in an inflammatory state and WM microstructure. Longitudinal trajectories of both measures were also examined separately for ECT-responders and non-responders. Patients exhibited elevated Interleukin-8 (IL-8) levels at baseline compared to controls. In patients, correlations between IL-8 and FAt changes from baseline to T2 were significant in the positive direction in the right superior longitudinal fasciculus (R-SLF) and right cingulum (R-CB) (psig = 0.003). In these tracts, linear mixed-effects models revealed that trajectories of IL-8 and FAt were significantly positively correlated across all time points in responders, but not non-responders (R-CB-p = .001; R-SLF-p = 0.008). Our results suggest that response to ECT in TRD may be mediated by IL-8 and WM microstructure.

P336. No Evidence for Changes in Brain Function After Electroconvulsive Therapy in Treatment-Resistant Depression: A Multicenter Study

With electroconvulsive therapy, induced epileptic seizures are known to be an effective treatment for major depressive episodes and to cause (temporary) structural grey matter increases in the brain. Small-sample study findings have been inconsistent in whether these structural increases relate to clinical improvement and/or functional brain changes that in turn may explain clinical outcome.

Ketamine for Adults With Treatment-Resistant Depression or Post-Traumatic Stress Disorder


 Two randomized controlled trials reported mixed evidence on the efficacy of repeated IV ketamine infusions for improving post-traumatic stress disorder. One randomized controlled trial with small sample size found that repeated IV ketamine infusions significantly improved post-traumatic stress disorder symptoms compared with midazolam in civilian population, while the other randomized controlled trial with larger sample size could not demonstrate a significant efficacy on post-traumatic stress disorder symptoms compared with placebo in military population. The antidepressant effects of ketamine were rapid, but the effects were not sustained after few weeks of post-treatment follow-up.
 One randomized controlled trial comparing IV ketamine with IV esketamine found both treatments had comparable acute antidepressant effects for treatment-resistant depression 24 hours following infusion.
 Two randomized controlled trials provided mixed evidence on the efficacy of single infusion of IV ketamine that was used as anesthetic agent for electroconvulsive therapy for treatment-resistant depression. One randomized controlled trial involving military population showed that patients undergoing electroconvulsive therapy for treatment-resistant depression with ketamine anesthesia had similar improvement of depression when compared with patients undergoing electroconvulsive therapy with methohexital anesthesia. However, in other randomized controlled trial comparing with propofol-based anesthesia in a civilian population, ketamine-based anesthesia provided faster improvement in depressive symptoms and fewer electroconvulsive therapy treatments to achieve disease remission.
 In a small randomized controlled trial, alternate infusions of subanesthetic dose of ketamine or midazolam with alternate electroconvulsive therapy showed no significant difference in antidepressant effects between groups.
 The efficacy of oral ketamine was demonstrated in 1 randomized controlled trial that repeated administration of oral ketamine significantly reduced depressive symptoms compared with placebo.
 A small retrospective chart review study showed that repeated administration of intramuscular ketamine had no significant differences in the improvement of depressive and anxiety symptoms compared with repeated transcranial magnetic stimulation.
 Findings suggest overall safety and tolerability of ketamine for treatment of post-traumatic stress disorder or treatment-resistant depression. Most frequent side effects associated with ketamine were dissociative symptoms and cardiovascular changes such as increased blood pressure and heart rate, but these effects were transient.
 The Danish guideline recommend against the use of IV ketamine in patients with treatment-resistant depression, due to low quality and insufficient evidence regarding the lack of long-term efficacy and the risk of abuse of ketamine. Likewise, the Canadian guideline recommends IV ketamine be considered as third-line treatment for adults with TRD, because of the short-lived efficacy of ketamine, its side effects, and the lack of strategies for relapse prevention after ketamine infusions.

The anticholinergic burden is not associated with cognitive impairments in patients treated by electroconvulsive therapy for treatment-resistant depression

Electroconvulsive therapy (ECT) is the most effective non-pharmacological treatment for treatment-resistant depression (TRD) but can expose to transient cognitive impairments. Understanding factors underlying these cognitive side effects is important. This study investigated the impact of anticholinergic treatments on cognitive performances after ECT courses for TRD in naturalistic condition. Impact of anticholinergic burden (Anticholinergic Impregnation Scale, AIS) on cognitive changes (Montreal Cognitive Assessment, MoCA) adjusted on depression level (Montgomery and Asberg Depression Scale, MADRS) was investigated in 42 patients who received an ECT course between 2017 and 2020 for unipolar or bipolar TRD. Collection of daily treatments given during ECT was carried out via the computerized traceability of treatments validated by nurses. Among the 31 treatments identified with an anticholinergic score, which represent only 38% of total treatments, the three most frequently given treatments were Lorazepam (47%), Venlafaxine (36%) and Cyamemazine (26%). Delayed recall was the most frequently impaired cognitive function after ECT courses. Using logistic regression, we found no association between the anticholinergic burden and the decrease in cognitive scores after ECT courses, adjusted on MADRS score evolution (p>0.1). Conversely, improvement in MADRS scores were correlated with improvement in attention MoCA subscores. This is a retrospective monocentric study with a moderate sample size using anticholinergic scales to calculate the anticholinergic burden without plasma dosage. Anticholinergic treatments did not seem to explain ECT-related cognitive impairments. This warrants further large prospective investigations including different measures of anticholinergic burden.

Serum Mature BDNF Level Is Associated with Remission Following ECT in Treatment-Resistant Depression.

The search for a biological marker predicting the future failure or success of electroconvulsive therapy (ECT) remains highly challenging for patients with treatment-resistant depression. Evidence suggests that Brain-Derived Neurotrophic Factor (BDNF), a protein known to be involved in brain plasticity mechanisms, can play a key role in both the clinical efficacy of ECT and the pathophysiology of depressive disorders. We hypothesized that mature BDNF (mBDNF), an isoform of BDNF involved in the neural plasticity and survival of neural networks, might be a good candidate for predicting the efficacy of ECT. Total BDNF (tBDNF) and mBDNF levels were measured in 23 patients with severe treatment-resistant depression before (baseline) they received a course of ECT. More precisely, tBDNF and mBDNF measured before ECT were compared between patients who achieved the criteria of remission after the ECT course (remitters, n = 7) and those who did not (non-remitters, n = 16). We found that at baseline, future remitters displayed significantly higher mBDNF levels than future non-remitters (p = 0.04). No differences were observed regarding tBDNF levels at baseline. The multiple logistic regression model controlled for age and sex revealed that having a higher baseline mBDNF level was significantly associated with future remission after ECT sessions (odd ratio = 1.38; 95% confidence interval = 1.07–2.02, p = 0.04). Despite the limitations of the study, current findings provide additional elements regarding the major role of BDNF and especially the mBDNF isoform in the clinical response to ECT in major depression.

Recent Updates on Electro-Convulsive Therapy in Patients with Depression

Objective Electro-convulsive therapy (ECT) has been established as a treatment modality for patients with treatment-resistant depression and with some specific subtypes of depression. This narrative review intends to provide psychiatrists with the latest findings on the use of ECT in depression, devided into total eight sub-topics. Methods We searched PubMed for English-language articles using combined keywords and tried to analyze journals published from 1995–2020. Results Pharmacotherapy such as antidepressants or maintenance ECT is more effective than a placebo as prevention of recurrence after ECT. The use of ECT in treatment-resistant depression, depressed patients with suicidal risks, elderly depression, bipolar depression, psychotic depression, and depression during pregnancy or postpartum have therapeutic benefits. As possible mechanisms of ECT, the role of neurotransmitters such as serotonin, dopamine, gamma-aminobutyric acid (GABA), and other findings in the field of neurophysiology, neuro-immunology, and neurogenesis are also supported. Conclusion ECT is evolving toward reducing cognitive side effects and maximizing therapeutic effects. If robust evidence for ECT through randomized controlled studies are more established and the mechanism of ECT gets further clarified, the scope of its use in the treatment of depression will be more expanded in the future.

Structural changes in amygdala nuclei, hippocampal subfields and cortical thickness following electroconvulsive therapy in treatment-resistant depression: longitudinal analysis.

Electroconvulsive therapy (ECT) is the treatment of choice for severe mental illness including treatment-resistant depression (TRD). Increases in volume of the hippocampus and amygdala following ECT have consistently been reported.AimsTo investigate neuroplastic changes after ECT in specific hippocampal subfields and amygdala nuclei using high-resolution structural magnetic resonance imaging (MRI) (trial registration: clinicaltrials.gov - NCT02379767). MRI scans were carried out in 14 patients (11 women, 46.9 years (s.d. = 8.1)) with unipolar TRD twice before and once after a series of right unilateral ECT in a pre-post study design. Volumes of subcortical structures, including subfields of the hippocampus and amygdala, and cortical thickness were extracted using FreeSurfer. The effect of ECT was tested using repeated-measures ANOVA. Correlations of imaging and clinical parameters were explored. Increases in volume of the right hippocampus by 139.4 mm3 (s.d. = 34.9), right amygdala by 82.3 mm3 (s.d. = 43.9) and right putamen by 73.9 mm3 (s.d. = 77.0) were observed. These changes were localised in the basal and lateral nuclei, and the corticoamygdaloid transition area of the amygdala, the hippocampal-amygdaloid transition area and the granule cell and molecular layer of the dentate gyrus. Cortical thickness increased in the temporal, parietal and insular cortices of the right hemisphere. Following ECT structural changes were observed in hippocampal subfields and amygdala nuclei that are specifically implicated in the pathophysiology of depression and stress-related disorders and retain a high potential for neuroplasticity in adulthood.Declaration of interestS.K. has received grants/research support, consulting fees and/or honoraria within the past 3 years from Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Celegne GmbH, Eli Lilly, Janssen-Cilag Pharma GmbH, KRKA-Pharma, Lundbeck A/S, Neuraxpharm, Pfizer, Pierre Fabre, Schwabe and Servier. R.L. received travel grants and/or conference speaker honoraria from Shire, AstraZeneca, Lundbeck A/S, Dr. Willmar Schwabe GmbH, Orphan Pharmaceuticals AG, Janssen-Cilag Pharma GmbH, and Roche Austria GmbH.

Cost-effectiveness modeling of repetitive transcranial magnetic stimulation compared to electroconvulsive therapy for treatment-resistant depression in Singapore

Background Compared to electroconvulsive therapy (ECT), the cost-effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the management of treatment-resistant depression (TRD) remains unclear. Objective/hypothesis This study evaluated the cost-effectiveness of rTMS vs. ECT for TRD from Singapore societal perspective. Methods We constructed a Markov model to project the cost and benefit of rTMS compared with ECT over one year in patients with TRD. The relative treatment effects between rTMS and ECT were obtained from meta-analyses of published trials. The effectiveness and quality of life data for patients using ECT, resource use for TRD and their associated costs were derived from the national tertiary mental institution in Singapore. Results At one year, rTMS was cost-effective relative to ECT. The incremental cost-effectiveness ratio (ICER) associated with ECT was Singapore dollars (SGD) 311,024 per quality-adjusted life-year (QALY) gained. This exceeded the willingness-to-pay threshold of SGD 70,000 per QALY gained. A similar trend was observed for ICER per remission achieved (i.e., SGD 143,811 per remission achieved with ECT). In the subgroup analysis, rTMS was found to be less costly and more effective than ECT in nonpsychotic depressive patients. In the scenario analysis, ECT employed as an ambulatory service yielded a much smaller ICER (i.e., SGD 78,819 per QALY gained) compared to the standard inpatient setting. Conclusions rTMS was a cost-effective treatment compared to ECT in TRD over one year. The cost-effectiveness of rTMS was attenuated when ECT was used in the outpatient setting.

Cost-Effectiveness Modeling of Repetitive Transcranial Magnetic Stimulation Compared to Electroconvulsive Therapy for Treatment-Resistant Depression in Singapore

Compared to electroconvulsive therapy (ECT), the cost-effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the management of treatment-resistant depression (TRD) remains unclear. This study evaluated the cost-effectiveness of rTMS vs. ECT for TRD from Singapore societal perspective. We constructed a Markov model to project the cost and benefit of rTMS compared with ECT over one year in patients with TRD. The relative treatment effects between rTMS and ECT were obtained from meta-analyses of published trials. The effectiveness and quality of life data for patients using ECT, resource use for TRD and their associated costs were derived from the national tertiary mental institution in Singapore. At one year, rTMS was cost-effective relative to ECT. The incremental cost-effectiveness ratio (ICER) associated with ECT was Singapore dollars (SGD) 311,024 per quality-adjusted life-year (QALY) gained. This exceeded the willingness-to-pay threshold of SGD 70,000 per QALY gained. A similar trend was observed for ICER per remission achieved (i.e., SGD 143,811 per remission achieved with ECT). In the subgroup analysis, rTMS was found to be less costly and more effective than ECT in nonpsychotic depressive patients. In the scenario analysis, ECT employed as an ambulatory service yielded a much smaller ICER (i.e., SGD 78,819 per QALY gained) compared to the standard inpatient setting. rTMS was a cost-effective treatment compared to ECT in TRD over one year. The cost-effectiveness of rTMS was attenuated when ECT was used in the outpatient setting.

Inflammation and Improvement of Depression Following Electroconvulsive Therapy in Treatment-Resistant Depression

Electroconvulsive therapy (ECT) is the most robust acute treatment for severe major depressive disorder, yet clinical response is variable. Inflammation is associated with depression, especially in women, and levels of C-reactive protein (CRP) and interleukin (IL)-6 predict response to antidepressant medications. This study evaluated whether markers of inflammation predicted response to electroconvulsive therapy (ECT) in patients with treatment-resistant depression and to what extent this association differed between men and women. In patients (N = 29) who had a current major depressive episode diagnosed using DSM-IV-TR criteria and were scheduled to undergo ECT at an academic referral center, levels of CRP, IL-6, IL-8, and tumor necrosis factor-α and severity of depressive symptoms (Montgomery-Asberg Depression Rating Scale [MADRS]) were prospectively evaluated before ECT treatment, after the second ECT session, and again at the completion of the index treatment series. Data were collected between December 2011 and December 2014. The primary outcome was end-of-treatment MADRS score. In multivariate analyses, higher levels of IL-6 at baseline, but not other inflammatory markers or clinical variables, were associated with lower end-of-treatment MADRS score (P = .01). When stratified by sex, IL-6 remained a significant predictor of end-of-treatment MADRS for women (P = .02) but not men (P = .1), and CRP emerged as a significant predictor for women (P = .04) but not men (P = .66). CRP and IL-6 increased from baseline to the second ECT session (P values < .01) and returned to baseline levels at end of treatment; these changes did not relate to MADRS score over the course of ECT. Levels of IL-6 prior to ECT treatment may be useful in identifying those depressed patients most likely to benefit from ECT treatment. In contrast, acute changes in IL-6 and CRP may reflect spikes in inflammatory response related to the initiation of seizure therapy, but not mood. Assessment of pretreatment inflammatory biomarkers, especially in women, might be useful in guiding treatment decision-making in treatment-resistant depression.

Manic switch in bipolar patients treated with electroconvulsive therapy for treatment-resistant depression: The experience at the mood disorder unit of Milan (Italy)

IntroductionDespite appropriate treatment, 30–40% of depressed patients, both unipolar and bipolar, do not achieve improvement, with high morbidity and mortality. For bipolar patients another risk is the switch into mania due to antidepressant treatment. The concern about the switch, suggests to administer antidepressants at lower doses, in combination with mood stabilizers and second generation anti-psychotics.ObjectivesWe performed an observational study on a sample of 23 bipolar patients treated with ECT for severe TRD in last 3 years, in order to evaluate the risk of switch.MethodsTwenty-three bipolar inpatients, undergoing bitemporal ECT twice/week, with MECTA spectrum device. Main demographic and clinical data collected. Hamilton rating scale for depression (HAM-D). Clinical response defined as 50% reduction of HAM-D score at the endpoint from baseline; remission as HAM-D score at the endpoint &lt; 8. Young Mania rating scale (YMRS) weekly in order to assess switch into mania.ResultsThirteen (56.5%) females, 10 (43.5%) males, mean age 60.1 ± 10.3 years. Mean age at onset 35.5 ± 13.6 years. Mean number of episodes: 7.1 ± 3.6. Mean duration of current episode: 33.4 ± 24.9 weeks. Mean HAM-D basal score: 30.0 ± 5. Each patient underwent a cycle of ECT (mean No. 6.7 ± 3.3). Pharmacological treatment was administered upon clinical need. Response rate 87%, remission rate 43.5%. Three out of 23 (13.04%) patients had transient hypomanic switch, spontaneous recovery within 7 days after the last ECT.ConclusionsOur experience confirms that ECT is a powerful antidepressant, especially in patients with severe long-lasting depression, refractory to treatment. ECT is also a safe procedure: no adverse effects were reported. The manic switch rate is comparable with antidepressant drugs.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Changes in dorsolateral prefrontal connectivity after rTMS in treatment-resistant depression: a brain perfusion SPECT study.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and safe alternative to electroconvulsive therapy for treatment-resistant depression (TRD). After rTMS, changes in brain SPECT perfusion have been remotely identified within medial temporal limbic areas, while no local effects have been found within the left dorsolateral prefrontal cortex (DLPFC)-i.e. under the coil. Functional changes in connectivity may underlie these remote effects. Interestingly, functional connectivity has been recently investigated using perfusion SPECT, and abnormalities identified in TRD patients. The aim of the present study is to evaluate perfusion and connectivity SPECT changes in TRD patients after rTMS of the left DLPFC. We hypothesize that changes in DLPFC networks may explain remote hypoperfusions found after rTMS. Fifty-eight TRD patients underwent a brain SPECT before and after high-frequency rTMS of the left DLPFC. Whole-brain voxel-based changes in perfusion were evaluated with SPM8, and inter-regional correlation analysis performed to study left DLPFC functional connectivity (p < 0.005, corrected for cluster volume). After rTMS, patients were significantly improved on Beck Depression Inventory score (p < 0.0001). Considering a 50% reduction threshold, 27 patients were identified as responders (47%). After rTMS, perfusion changes were not found locally within the left DLPFC, but remotely within the bilateral temporal lobes, including limbic areas. Inter-regional correlation SPECT analysis brings out a decrease of connectivity between the left DLPFC and both the cingulate/medial frontal cortex and bilateral medial temporal limbic areas, in relation with the clinical response. rTMS of DLPFC in TRD patients leads to remote temporal hypoperfusions in relation with changes in functional connectivity between the DLPFC and the default mode network, especially including medial temporal limbic areas.