Older age associated with better antidepressant response to H1-coil transcranial magnetic stimulation in female patients.

BACKGROUND: TMS is increasingly used to treat depression, but predictors of treatment outcomes remain unclear. We assessed the association between age and TMS response given inconsistent prior reports limited by small sample size, heterogeneity, outdated TMS parameters, lack of assessment of H1-coil TMS, and lack of an a priori hypothesis. We hypothesized that older age would be associated with better treatment response based on trends in recent large exploratory analyses. METHODS: We conducted a naturalistic retrospective analysis of patients (n = 378) ages 18-80 with depression (baseline Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) > 5) who received 29-35 sessions of TMS between 2014 and 2021. Response was assessed using percent reduction of QIDS-SR. The relationship between percent response or remission and age group was assessed using the chi-square test. RESULTS: 85 % of patients received the standard protocol of H1-coil TMS to the left DLPFC. Percent response and remission rates for the entire study sample increased with age (response: p = .026; remission: p = .0023). This finding was stronger in female patients (response: p = .0033; remission: p = .00098) and was not observed in male patients (response: p = .73; remission: p = .26). This was confirmed in a sub-analysis of patients who only received the standard protocol with the H1-coil for the entire treatment course. LIMITATIONS: Naturalistic retrospective analysis from one academic center. CONCLUSIONS: Older age is associated with a better antidepressant response to H1-coil TMS in female patients. This was demonstrated in a hypothesis-driven confirmation of prior exploratory findings in a large sample size with a homogeneous data collection protocol across all participants.

A Novel Approach to Monitoring Cognitive Adverse Events for Interventional Studies Involving Advanced Dementia Patients: Insights From the Electroconvulsive Therapy for Agitation in Dementia Study.

OBJECTIVE: To develop an individualized method for detecting cognitive adverse events (CAEs) in the context of an ongoing trial of electroconvulsive therapy for refractory agitation and aggression for advanced dementia (ECT-AD study). METHODS: Literature search aimed at identifying (a) cognitive measures appropriate for patients with advanced dementia, (b) functional scales to use as a proxy for cognitive status in patients with floor effects on baseline cognitive testing, and (c) statistical approaches for defining a CAE, to develop CAEs monitoring plan specifically for the ECT-AD study. RESULTS: Using the Severe Impairment Battery-8 (SIB-8), baseline floor effects are defined as a score of ≤5/16. For patients without floor effects, a decline of ≥6 points is considered a CAE. For patients with floor effects, a decline of ≥30 points from baseline on the Barthel Index is considered a CAE. These values were derived using the standard deviation index (SDI) approach to measuring reliable change. CONCLUSIONS: The proposed plan accounts for practical and statistical challenges in detecting CAEs in patients with advanced dementia. While this protocol was developed in the context of the ECT-AD study, the general approach can potentially be applied to other interventional neuropsychiatric studies that carry the risk of CAEs in patients with advanced dementia.

Efficacy and safety of ketamine-assisted electroconvulsive therapy in major depressive episode: a systematic review and network meta-analysis.

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

Residual symptoms following electroconvulsive therapy: A retrospective cohort study.

BACKGROUND: Residual depressive symptoms following treatment are a burden for patients and are associated with increased risk of relapse. While this phenomenon has been explored following pharmacotherapy, there is little research into residual symptoms following electroconvulsive therapy (ECT). This study quantifies the frequency and type of residual symptoms following ECT treatment. METHODS: This study used retrospective data from patients receiving ECT as part of routine clinical care. Depressive symptomatology was assessed using the Quick Inventory of Depressive Symptomatology - Self-Report 16 item scale (QIDS), which includes 9 symptom domains graded from 0 to 3. We quantified the frequency of mild or greater (QIDS≥1) and moderate or greater (QIDS ≥ 2) residual symptoms following treatment among patients responding to ECT (QIDS decrease ≥50 % from baseline) and non-responders (QIDS decrease <50 %). RESULTS: Among 1799 patients, 1015 (56.4 %) responded to ECT and 784 (43.6 %) did not. Among responders, 99.5 % had at least one residual symptom of mild severity or greater (median = 5, IQR = 3-6) and 83.3 % had at least one residual symptom of moderate severity or greater (median = 1, IQR = 1-2). Among non-responders, 100 % had residual symptoms of mild severity or greater (median = 8, IQR = 7-9), and 99.2 % had a residual symptom of moderate severity or greater (median = 4, IQR = 3-5). The most common residual symptoms among both responders and non-responders were sleep disturbances (93.1 % and 98.7 %, respectively) and sadness (68.9 % and 96.4 %, respectively). LIMITATIONS: Retrospective data from a single freestanding psychiatric hospital. CONCLUSION: Among patients with depression receiving ECT, there were high rates of residual symptoms even among patients responding to treatment.

Changes in self-reported suicidal ideation during treatment with electroconvulsive therapy: A retrospective cohort study.

OBJECTIVE: Suicidal ideation (SI) is common in patients with depressive symptoms, who are the most common recipients of electroconvulsive therapy (ECT). We sought to quantify changes in self-reported SI occurring during treatment with ECT, and to identify factors associated with persistence of SI in patients beginning treatment with SI. METHOD: Retrospective, single-center cohort study of patients receiving ECT and who self-reported symptoms using Quick Inventory of Depressive Symptomatology (QIDS) prior to ECT and after treatment #5 or #10. Changes in QIDS-reported SI over the course of ECT were calculated, and logistic regression models were performed to assess factors associated with reporting SI at the end of treatment. RESULTS: 2554 provided baseline and follow-up SI scores, of whom, 1931 (75.6%) endorsed SI at baseline. There was a reduction in SI with ECT treatment (McNemar's test; df = 1, Χ2 = 803.7; p < 0.001), and in adjusted models 64.0% of individuals with baseline SI reported resolution of SI with ECT treatment, while 3.3% without baseline SI reported SI at the end of treatment. Higher baseline SI severity and outpatient treatment were associated with a higher odds of persistent SI among individuals beginning treatment with SI. CONCLUSION: Electroconvulsive therapy treatment was associated with reductions in self-reported SI. These results support the use of ECT in the treatment of patients with SI, but further research is needed to determine the effects of ECT on suicidal behavior.

A Pilot Study of Adjunctive Group Therapy to Enhance Coping With Cognitive Challenges and Support Cognitive Health After Electroconvulsive Therapy.

OBJECTIVES: Concerns about the cognitive adverse effects of electroconvulsive therapy (ECT) are common among recipients of the treatment despite its relatively small adverse effects on cognitive functioning. Interventions aimed at remediating or improving coping with cognitive adverse effects of ECT have not been developed. The Enhancing Cognitive Domains after ECT (ENCODE) program is a new group intervention aimed at teaching self-management strategies to cope with the cognitive challenges and associated anxiety that often accompanies ECT. METHODS: This pilot study used a pretest-posttest design to examine the feasibility and clinical utility of delivering ENCODE to 20 adults who had received ECT in a hospital-based ECT program. RESULTS: The program was found to be both feasible and acceptable as indicated by the attainment of recruitment targets, high rates of attendance (85% of participants attended at least 5 of the 6 group sessions), and high participant satisfaction ratings (88% reported that ENCODE helped or helped very much to manage their cognitive challenges). The clinical utility of the program was suggested by reductions in depressive symptom severity and subjective memory complaints. Nonsignificant improvements were observed in global cognitive function and cognitive self-efficacy. CONCLUSIONS: This study provides preliminary evidence for the feasibility and clinical utility of ENCODE based on program demand, strong participant satisfaction, and postgroup reductions in distress and subjective memory complaints.

Factors associated with early and late response to electroconvulsive therapy.

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective treatment for severe depressive symptoms, yet more research is needed to examine predictors of treatment response, and factors associated with response in patients not initially improving with treatment. This study reports factors associated with time to response (early vs. late) to ECT in a real-world setting. METHODS: This was a retrospective, single-center cohort study of patients endorsing moderate to severe depressive symptoms using the Quick Inventory of Depressive Symptomatology (QIDS; QIDS>10). Response was defined as 50% or greater decrease in QIDS score from baseline. We used logistic regression to predict response at treatment #5 (early response) as well as after treatment #5 (late response) and followed patients through ECT discontinuation or through treatment #20. RESULTS: Of the 1699 patients included in this study, 555 patients (32.7%) responded to ECT treatment at treatment #5 and 397 (23.4%) responded after treatment #5. Among patients who did not respond by treatment #5, those who switched to brief pulse width ECT from ultrabrief pulse ECT had increased odds of response after treatment #5 compared with patients only receiving ultrabrief pulse (aOR = 1.55, 95% CI: 1.16-2.07). Additionally, patients with less improvement in QIDS from baseline to treatment #5 had decreased odds of response after treatment #5 (aOR = 0.97, 95% CI = 0.97-0.98). CONCLUSION: Among depressed patients treated with ECT, response occurred in 56.0% of patients by treatment #20. Patient receiving ultrabrief pulse ECT at baseline and who did not respond by treatment #5 had greater odds of subsequent response if switched to brief pulse ECT than if continued with ultrabrief pulse.

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

ABSTRACT: 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 Duration in Treatment With Electroconvulsive Therapy Among Patients Screening Positive or Negative for Borderline Personality Disorder Traits: A Retrospective Cohort Study.

OBJECTIVE: While emerging evidence suggests that electroconvulsive therapy (ECT) is an effective treatment for depressive symptoms in patients with co-occurring borderline personality disorder (BPD) traits, it is unclear whether the presence of BPD traits modulates the tolerability of ECT. This study estimates the association between BPD traits and retention in acute course ECT treatment. METHODS: This study used a retrospective cohort of patients receiving ECT between 2015 and 2020 and who were assessed using the McLean Screening Instrument for BPD, the Quick Inventory of Depressive Symptomatology Self-Report 16-item scale, and the Montreal Cognitive Assessment before initiating treatment. RESULTS: One thousand five hundred eight patients received ECT during the study period, of whom 277 (18.4%) screened positive for BPD traits. Borderline personality disorder traits were associated with a higher odds of remaining in ECT for at least 10 treatments (adjusted odds ratio, 1.502; 95% confidence interval, 1.11-2.02; P = 0.007). Among individual symptom domains, only endorsing chronically feeling empty was associated with duration in ECT treatment. CONCLUSIONS: Among patients receiving ECT, screening positive for BPD traits was associated with a higher odds of receiving at least 10 ECT treatments. These results support the overall tolerability of ECT in patients with BPD traits.

Simulated Electroconvulsive Therapy: A Novel Approach to a Control Group in Clinical Trials.

OBJECTIVES: Agitation is the most common behavioral symptom of Alzheimer disease (AD) affecting approximately 40% to 60% of the AD population, yet there are no Food and Drug Administration-approved therapies for the myriad of behavioral or psychological symptoms of dementia. There is growing evidence from naturalistic studies that electroconvulsive therapy (ECT) is a safe and effective treatment for agitation in AD patients who are refractory to pharmacotherapy and behavioral interventions. Despite the existing evidence, ECT remains underused because of stigma, lack of education, and concerns regarding adverse cognitive effects. Randomized controlled clinical trials of ECT are an opportunity to provide high-quality evidence of ECT as a safe and efficacious treatment for agitation in the AD population. We describe the methods for the Electroconvulsive Therapy in Alzheimer's Dementia study, which uses a novel, simulated ECT (S-ECT) control group to conduct a single-blind efficacy study of ECT for the treatment of agitation and aggression in individuals with moderate to severe AD. METHODS: We discuss the rationale, study design, methodology, ethical and practical challenges, and management strategies in using an S-ECT group as the comparator arm in this randomized controlled trial of ECT in AD-related treatment refractory agitation and aggression. CONCLUSIONS: Validation of the safety and efficacy of ECT in patients with advanced AD with refractory agitation and aggression is necessary. This can be accomplished through creative formulation of S-ECT groups that effectively maintain the blind while providing scientific integrity.

The Effects of Baseline Impaired Global Cognitive Function on the Efficacy and Cognitive Effects of Electroconvulsive Therapy in Geriatric Patients: A Retrospective Cohort Study.

OBJECTIVES: This study explores the association between baseline impaired global cognitive function and changes in global cognitive function and depression among geriatric patients undergoing acute course electroconvulsive therapy (ECT). DESIGN: Retrospective cohort study. SETTING: Single freestanding psychiatric hospital. PARTICIPANTS: Patients aged 50 and older receiving ECT. INTERVENTIONS: 10 ECT treatments. MEASUREMENTS: Cognitive assessments with the Montreal Cognitive Assessment (MoCA). Depression assessment with the Quick Inventory of Depressive Symptomatology Self Report 16 item scale (QIDS). RESULTS: Baseline and follow-up data were available for 684 patients. On average, patients with baseline normal cognition (MoCA ≥26; N = 371) had a decrease in MoCA of -1.44±0.26 points over the course of treatment, while those with baseline impaired global cognitive function (MoCA <26; N = 313) had an increase in MoCA of 1.72±0.25 points. Baseline cognitive status was not associated with a differential response on the QIDS. CONCLUSIONS: Patients with baseline impaired global cognitive function did not demonstrate a worsening in cognition following ECT, and baseline global cognitive function was not associated with a differential change in depression with ECT. These results suggest that impaired global cognitive function should not be viewed as a contraindication to ECT in geriatric patients.

First Acute-Course Electroconvulsive Therapy for Moderate-to-Severe Depression Benefits Patients With or Without Accompanying Baseline Cognitive Impairment.

BACKGROUND: Researchers are increasingly investigating therapeutic response associated with new patient subgroups as a way to improve electroconvulsive therapy (ECT) treatment outcomes and reduce adverse events. This study is the first to examine baseline cognitive impairment status as a predictor of clinical outcome in first acute-course ECT patients. METHODS: Baseline cognitive function at various thresholds and serial depressive symptom severity data from first-time ECT patients were examined using generalized linear mixed-effects models. RESULTS: Of 1345 patients who met the inclusion criteria, 617 had available data at their third assessment visit (~15th treatment visit). There was a robust improvement in depression symptoms over time (P < 0.0001), and cognitive function was not associated with baseline levels of depressive symptoms or serially measured change in self-reported symptom severity during acute-phase ECT. CONCLUSIONS: These results indicate that an acute course of ECT for the treatment of moderate-to-severe depression benefits patients with or without accompanying baseline cognitive impairment. These findings may be useful in informing shared decision-making discussions about ECT risks and expected benefits.

Real-world evidence of age-independent electroconvulsive therapy efficacy: A retrospective cohort study.

OBJECTIVES: Electroconvulsive therapy (ECT) is an effective treatment for depressive disorders and approved for use in adolescents and adults, but it is unclear whether efficacy or cognitive side effect burden differs with age or if effectiveness in usual clinical practice matches that in prospective studies. We examined the effects of ECT on depression and cognition in a large clinical cohort. METHODS: A retrospective cohort study of patients ages 16 and older receiving ECT between 2011 and 2020 and who were evaluated with the Quick Inventory of Depressive Symptomatology (QIDS), the Behavior and Symptom Identification Scale-24 (BASIS-24), and the Montreal Cognitive Assessment (MoCA) at baseline and after treatment #10. RESULTS: Among 1698 patients, ECT was associated with a decrease in depression symptoms (QIDS reduction from 17.1 ± 4.9 to 10.1 ± 5.2) and improvement in self-reported mental health (BASIS-24 scores improved from 1.92 ± 0.55 to 1.17 ± 0.60). There was a reduction in MoCA scores from 25.8 ± 3.1 to 25.4 ± 3.1. In multivariate models, age was not associated with a differential QIDS or BASIS-24 response, but older age was associated with a lesser reduction in MoCA. CONCLUSION: Among 1698 patients aged 16 and older, ECT was associated with improvement in depression and overall self-reported mental health, with a slight decrease in cognition. Age was not associated with changes in efficacy, but older age was associated with a lesser cognitive change as measured by the MoCA. These results provide normative data of real-world effectiveness of ECT, and add further support to its utility in patients with severe psychiatric illness.

Individual response to electroconvulsive therapy is not correlated between multiple treatment courses.

OBJECTIVES: Electroconvulsive therapy (ECT) effectively treats depressive disorders, but many patients will have subsequent relapses. While some guidelines suggest prior response to ECT is an indication for ECT in a subsequent mood episode, it is unknown whether response to ECT is correlated between treatment courses. This study explores whether response to ECT at a first treatment correlates with response to treatment in a second independent ECT course. METHODS: Single-center retrospective cohort of patients receiving two different ECT treatment courses between 2011 and 2020 and who self-reported depression symptoms using the Quick Inventory of Depressive Symptomatology (QIDS) at baseline and following treatment #5. RESULTS: 286 patients received two independent ECT series during the study period, of whom 153 received at least 5 treatments in both series. Patients had similar QIDS scores at the start of each treatment series (Pearson's correlation, r = 0.58, p <0.001), but the change in QIDS following 5 ECT treatments was not correlated between series for individual patients (Pearson's correlation, r = 0.083, p = 0.31). In multivariate analyses, change in QIDS was similar for both treatment series, but patients were less likely to receive 5 treatments in the second treatment series. LIMITATIONS: retrospective cohort cannot control for factors influencing access to repeat ECT treatment CONCLUSIONS: While on average final QIDS score was the same following two independent treatment courses, for individual patients the change in depression symptoms was not correlated between treatment series. Further research is needed to identify factors that may predict longitudinal ECT response.

Treatment of Electroconvulsive Therapy-Emergent Hypomania and Mania: A Systematic Review of the Literature.

Objective: Electroconvulsive therapy (ECT)-emergent hypomania/mania is a clinically significant problem that has lacked evidence-based guidelines for effective management. The aim of this systematic literature review is to compile the current published literature on treating ECT-emergent hypomania/mania to help guide treatment course in patients with unipolar and bipolar depression.Data Sources: MEDLINE/PubMed was searched for studies published from 1980 through August 2020 that evaluated the treatment of ECT-emergent hypomania/mania. Search terms included Boolean combinations of the following: mania, hypomania, ECT, ECT induced mania, and ECT induced hypomania.Study Selection: There were 1,662 articles reviewed, and all published studies detailing the treatment of ECT-emergent hypomania/mania written in English that met inclusion criteria were included. Due to the limited number of articles, there were no restrictions.Data Extraction: Two reviewers extracted relevant articles and assessed each study based on inclusion criteria.Results: The literature review identified 12 articles that described the treatment course of ECT-emergent hypomania/mania in 17 patients. There were 9 patients who had no known history of manic or hypomanic episodes and were diagnosed with unipolar depression and 8 patients diagnosed with bipolar disorder. There were 4 primary treatment courses identified: continuing ECT alone, continuing ECT in conjunction with lithium, discontinuing ECT with no medication treatment, or discontinuing ECT and starting a medication.Conclusions: The available data are insufficient to support definitive conclusions; however, potential treatment guidelines are suggested within the review to providers based on the limited data available.

The Efficacy and Cognitive Effects of Acute Course Electroconvulsive Therapy Are Equal in Adolescents, Transitional Age Youth, and Young Adults.

Objective: Electroconvulsive therapy (ECT) is the most effective acute treatment for depression, but its use in younger patients is rare and heavily regulated in many U.S. states. It is unclear whether age modifies treatment response or tolerability in adolescents, transitional age youth, and young adults. We examined the effects of ECT on depression and cognition in patients aged 16-30 years. Methods: A retrospective cohort study of patients aged 16-30 years receiving ECT between 2011 and 2020 who were evaluated with the Quick Inventory of Depressive Symptomatology (QIDS), the Behavior and Symptom Identification Scale-24 (BASIS-24), and the Montreal Cognitive Assessment (MoCA) at baseline and following treatment #10. Results: Among the 424 patients who met the inclusion criteria, ECT was associated with a decrease in depression symptoms (ΔQIDS -6.7; Kruskal-Wallis rank sum test; χ2 = 293.37; df = 2; p < 0.0001) and improvement in overall self-reported mental health status (ΔBASIS-24 - 0.70; Kruskal-Wallis rank sum test; χ2 = 258.5; df = 2; p < 0.0001) during the first 10 treatments, with a slight reduction in cognition as measured by the MoCA (ΔMoCA -1.1; Kruskal-Wallis rank sum test; χ2 = 33.7; df = 1; p < 0.0001). Age was not a significant predictor of QIDS, BASIS-24, or MoCA changes. Conclusions: Among 424 patients aged 16-30 years receiving acute course ECT, age was not a significant predictor of improvement in depression, change in overall self-reported mental health status, or change in cognition. These results support the utility of ECT in the treatment of adolescents and young adults.