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.

Outcomes of electroconvulsive therapy in patients with depressive symptoms with versus without comorbid personality disorders/traits: A systematic review and meta-analysis.

AIMS: To assess electroconvulsive therapy (ECT) outcomes in patients affected by depressive symptoms with versus without additional comorbid personality disorders/traits. METHODS: We identified observational studies investigating ECT clinical outcomes in patients affected by depressive symptoms with versus without comorbid personality disorders/traits in Embase/Medline in 11/2022. Our protocol was registered with PROSPERO (CRD42023390833). Study quality was evaluated using the Newcastle-Ottawa-Scale. Our primary outcomes were ECT response and remission rates. Meta-regression analyses included effects of in/outpatient percentages, age, number of ECT sessions, and electrode placement; subgroup analyses included the assessment methods for personality disorders/traits. We performed sensitivity analyses after excluding poor-quality studies. RESULTS: A total of 20 studies (n = 11,390) were included in our analysis. Patients with comorbid personality disorders/traits had lower remission rates (OR = 0.42, 95% CI = 0.31, 0.58, p < 0.001) with substantial heterogeneity (I2 = 93.0%) as well as lower response rates (OR = 0.35, 95% CI = 0.24, 0.51, n = 5129, p < 0.001) with substantial heterogeneity (I2 = 93.0%) compared with patients without comorbid personality disorders/traits. Relapse rates were higher in patients with versus without comorbid personality disorders/traits (OR = 3.23, 95% CI = 1.40, 7.45, k = 4, n = 239, p = 0.006) with moderate heterogeneity (I2 = 75.0%) and post-ECT memory impairment was more frequent in patients with versus without comorbid personality disorders/traits (OR = 1.41, 95% CI = 1.36, 1.46, k = 4, n = 471, p < 0.001) with minimal heterogeneity (I2 = 0.0%). Dropout rates were higher in patients with versus without comorbid personality disorders/traits (OR = 1.58, 95% CI = 1.13, 2.21, k = 3, n = 6145, p = 0.008). CONCLUSIONS: Patients with comorbid personality disorders/traits treated with ECT are reported to have lower response and remission rates and higher rates of side effects and relapse rates compared with patients without personality disorders/traits.

Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression.

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this causal depression network (CDN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis Principal Component Analysis (PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CDN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CDN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes (t = -2.35, p = 0.019). This evidence further supports that treatment interventions converge on a CDN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.

Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression.

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this common causal network (CCN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis (Principal Component Analysis, PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CCN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CCN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes. This evidence further supports that treatment interventions converge on a CCN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.

Consultation-Liaison Case Conference: Malignantly Catatonic and Unable to Receive Electroconvulsive Therapy.

We present the case of a 65-year-old female with a past psychiatric history of obsessive-compulsive disorder and anxiety who recently underwent diagnostic laparoscopy in the setting of a recent computerized tomography scan revealing a peritoneal mass. Postoperatively, she was delirious and soon found to be malignantly catatonic. This patient's treatment was complicated by an acute stroke, which was a relative contraindication for electroconvulsive therapy. Top experts in the consultation-liaison psychiatry and electroconvulsive therapy fields provide guidance for this clinical scenario based on their experience and a review of the available literature. Key teaching points include a review of diagnosing and treating catatonia, a review of electroconvulsive therapy for the treatment of catatonia, as well as a review of the role of the consultation-liaison psychiatrist in medically complex cases. Specifically, we offer guidance in treating patients that have malignant catatonia when electroconvulsive therapy is unavailable.

Adolescents and Young Adults With Anti-N-methyl-D-aspartate Receptor Encephalitis With Excited Catatonia: Literature Review and 2 Illustrative Cases.

BACKGROUND: Catatonia is a complex neuropsychiatric syndrome that can be associated with several underlying etiologies including primary psychiatric and autoimmune disorders. Anti-N-methyl-D-aspartate receptor encephalitis is an autoimmune disorder typically characterized by seizures, movement abnormalities, and behavioral changes. Anti-N-methyl-D-aspartate can present with complex neuropsychiatric symptoms including catatonia which can be challenging for clinicians to identify as excited catatonia can mimic delirium and psychiatric disorders such as psychosis and mania. OBJECTIVES: To identify and present cases of anti-N-methyl-D-aspartate receptor encephalitis where excited catatonia is the presenting symptom. METHODS: We present 2 case studies of agitation and disinhibition in an adolescent and young adult that were ultimately found to be secondary to autoimmune receptor encephalitis, in both cases, confirmed by cerebrospinal fluid analysis to be due to anti-N-methyl-D-aspartate receptor antibodies. RESULTS: Excited catatonia was suspected and initially treated with immunological therapy and high doses of lorazepam. As the severity of catatonia progressed with limited improvement with lorazepam, both cases were ultimately effectively treated with electroconvulsive therapy. CONCLUSIONS: Excited catatonia should be considered with presentations of bizarre behavior, agitation, disinhibition, and other psychotic symptoms in patients with no prior psychiatric history. Although the primary treatment for catatonia associated with anti-N-methyl-D-aspartate receptor encephalitis is immunomodulatory therapy paired with benzodiazepines, electroconvulsive therapy has been shown to be an effective and safe adjuvant treatment that is especially useful for management of excited catatonia.

Brain stimulation and other biological non-pharmacological interventions in mental disorders: An umbrella review.

BACKGROUND: The degree of efficacy, safety, quality, and certainty of meta-analytic evidence of biological non-pharmacological treatments in mental disorders is unclear. METHODS: We conducted an umbrella review (PubMed/Cochrane Library/PsycINFO-04-Jul-2021, PROSPERO/CRD42020158827) for meta-analyses of randomized controlled trials (RCTs) on deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), electro-convulsive therapy (ECT), and others. Co-primary outcomes were standardized mean differences (SMD) of disease-specific symptoms, and acceptability (for all-cause discontinuation). Evidence was assessed with AMSTAR/AMSTAR-Content/GRADE. RESULTS: We selected 102 meta-analyses. Effective interventions compared to sham were in depressive disorders: ECT (SMD=0.91/GRADE=moderate), TMS (SMD=0.51/GRADE=moderate), tDCS (SMD=0.46/GRADE=low), DBS (SMD=0.42/GRADE=very low), light therapy (SMD=0.41/GRADE=low); schizophrenia: ECT (SMD=0.88/GRADE=moderate), tDCS (SMD=0.45/GRADE=very low), TMS (prefrontal theta-burst, SMD=0.58/GRADE=low; left-temporoparietal, SMD=0.42/GRADE=low); substance use disorder: TMS (high frequency-dorsolateral-prefrontal-deep (SMD=1.16/GRADE=moderate), high frequency-left dorsolateral-prefrontal (SMD=0.77/GRADE=very low); OCD: DBS (SMD=0.89/GRADE=moderate), TMS (SMD=0.64/GRADE=very low); PTSD: TMS (SMD=0.46/GRADE=moderate); generalized anxiety disorder: TMS (SMD=0.68/GRADE=low); ADHD: tDCS (SMD=0.23/GRADE=moderate); autism: tDCS (SMD=0.97/GRADE=very low). No significant differences for acceptability emerged. Median AMSTAR/AMSTAR-Content was 8/2 (suggesting high-quality meta-analyses/low-quality RCTs), GRADE low. DISCUSSION: Despite limited certainty, biological non-pharmacological interventions are effective and safe for numerous mental conditions. Results inform future research, and guidelines. FUNDING: None.

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.

Longitudinal Neurocognitive Effects of Combined Electroconvulsive Therapy (ECT) and Pharmacotherapy in Major Depressive Disorder in Older Adults: Phase 2 of the PRIDE Study.

OBJECTIVE: There is limited information regarding neurocognitive outcomes of right unilateral ultrabrief pulse width electroconvulsive therapy (RUL-UB ECT) combined with pharmacotherapy in older adults with major depressive disorder. We report longitudinal neurocognitive outcomes from Phase 2 of the Prolonging Remission in Depressed Elderly (PRIDE) study. METHOD: After achieving remission with RUL-UB ECT and venlafaxine, older adults (≥60 years old) were randomized to receive symptom-titrated, algorithm-based longitudinal ECT (STABLE) plus pharmacotherapy (venlafaxine and lithium) or pharmacotherapy-only. A comprehensive neuropsychological battery was administered at baseline and throughout the 6-month treatment period. Statistical significance was defined as a p-value of less than 0.05 (two-sided test). RESULTS: With the exception of processing speed, there was statistically significant improvement across most neurocognitive measures from baseline to 6-month follow-up. There were no significant differences between the two treatment groups at 6 months on measures of psychomotor processing speed, autobiographical memory consistency, short-term and long-term verbal memory, phonemic fluency, inhibition, and complex visual scanning and cognitive flexibility. CONCLUSION: To our knowledge, this is the first report of neurocognitive outcomes over a 6-month period of an acute course of RUL-UB ECT followed by one of 2 strategies to prolong remission in older adults with major depression. Neurocognitive outcome did not differ between STABLE plus pharmacotherapy versus pharmacotherapy alone over the 6-month continuation treatment phase. These findings support the safety of RUL-UB ECT in combination with pharmacotherapy in the prolonging of remission in late-life depression.

A Role for Electroconvulsive Therapy in the Management of New Onset Refractory Status Epilepticus (NORSE) in a Young Child.

New-onset refractory status epilepticus (NORSE) describes prolonged or recurring new onset seizures which fail to respond to antiseizure medications. NORSE poses a challenge in diagnosis and treatment, and limited high-quality evidence exists to guide management. The efficacy of Electroconvulsive therapy (ECT) in aborting refractory status epilepticus has been described in case reports, but its application remains uncommon, particularly in young children. We describe a case of NORSE in a 3-year old child in which ECT played an important role in aborting status epilepticus, facilitating the diagnosis and surgical excision of an underlying focal cortical dysplasia. Although further research is needed, our case suggests that ECT can be a valuable tool in the treatment of refractory status epilepticus in children.

ECT-induced cognitive side effects are associated with hippocampal enlargement.

Electroconvulsive therapy (ECT) is of the most effective treatments available for treatment-resistant depression, yet it is underutilized in part due to its reputation of causing cognitive side effects in a significant number of patients. Despite intensive neuroimaging research on ECT in the past two decades, the underlying neurobiological correlates of cognitive side effects remain elusive. Because the primary ECT-related cognitive deficit is memory impairment, it has been suggested that the hippocampus may play a crucial role. In the current study, we investigated 29 subjects with longitudinal MRI and detailed neuropsychological testing in two independent cohorts (N = 15/14) to test if volume changes were associated with cognitive side effects. The two cohorts underwent somewhat different ECT study protocols reflected in electrode placements and the number of treatments. We used longitudinal freesurfer algorithms (6.0) to obtain a bias-free estimate of volume changes in the hippocampus and tested its relationship with neurocognitive score changes. As an exploratory analysis and to evaluate how specific the effects were to the hippocampus, we also calculated this relationship in 41 other areas. In addition, we also analyzed cognitive data from a group of healthy volunteers (N = 29) to assess practice effects. Our results supported the hypothesis that hippocampus enlargement was associated with worse cognitive outcomes, and this result was generalizable across two independent cohorts with different diagnoses, different electrode placements, and a different number of ECT sessions. We found, in both cohorts, that treatment robustly increased the volume size of the hippocampus (Cohort 1: t = 5.07, Cohort 2: t = 4.82; p < 0.001), and the volume increase correlated with the neurocognitive T-score change. (Cohort 1: r = -0.68, p = 0.005; Cohort 2: r = -0.58; p = 0.04). Overall, our research indicates that novel treatment methods serving to avoid hippocampal volume increase may result in a better side effect profile.

Electroconvulsive Therapy Practice Changes in Older Individuals Due to COVID-19: Expert Consensus Statement.

The ubiquitous coronavirus 2019 (COVID-19) pandemic has required healthcare providers across all disciplines to rapidly adapt to public health guidelines to reduce risk while maintaining quality of care. Electroconvulsive therapy (ECT), which involves an aerosol-generating procedure from manual ventilation with a bag mask valve while under anesthesia, has undergone drastic practice changes in order to minimize disruption of treatment in the midst of COVID-19. In this paper, we provide a consensus statement on the clinical practice changes in ECT specific to older adults based on expert group discussions of ECT practitioners across the country and a systematic review of the literature. There is a universal consensus that ECT is an essential treatment of severe mental illness. In addition, there is a clear consensus on what modifications are imperative to ensure continued delivery of ECT in a manner that is safe for patients and staff, while maintaining the viability of ECT services. Approaches to modifications in ECT to address infection control, altered ECT procedures, and adjusting ECT operations are almost uniform across the globe. With modified ECT procedures, it is possible to continue to meet the needs of older patients while mitigating risk of transmission to this vulnerable population.

Electroconvulsive therapy (ECT) for moderate-severity major depression among the elderly: Data from the pride study.

BACKGROUND: Electroconvulsive therapy (ECT) is usually reserved for treatment of severe major depressive disorder (MDD), but may be equally effective in the treatment of moderate-severity MDD. This possibility, however, has only been studied to a very limited extent. We therefore investigated the efficacy of ECT after stratifying patients into severe MDD and moderate-severity MDD. METHODS: We used data from the Prolonging Remission in Depressed Elderly (PRIDE) study, in which 240 patients (≥60 years) with MDD were treated with right unilateral ultrabrief pulse ECT, combined with venlafaxine. We used the six-item core depression subscale (HAM-D6) of the Hamilton Depression Rating Scale to define depression severity. Participants with baseline total scores ≥12 on the HAM-D6 were considered to have severe MDD, while those with HAM-D6 total scores <12 were considered to have moderate-severity MDD. RESULTS: Among the participants with severe MDD and moderate-severity MDD, the mean change in the HAM-D6 total score from baseline to endpoint was -8.2 (95% confidence interval (95%CI) = -7.5; -9.0, paired t-test: p < 0.001) and -5.9 (95%CI = -5.1; -6.6, paired t-test: p < 0.001), respectively. A total of 63% of those with severe MDD and 75% of those with moderate-severity MDD achieved remission (HAM-D6 total score ≤4) (Pearson's 2-sample chi-squared test of difference between groups: p = 0.27). LIMITATIONS: The PRIDE study was not designed to address this research question. CONCLUSIONS: ECT combined with venlafaxine appears to be an effective treatment for moderate-severity MDD. It may be appropriate to expand the indications for ECT to include patients with moderate-severity MDD.

Prolactin changes during electroconvulsive therapy: A systematic review and meta-analysis.

BACKGROUND: Early studies reported a prolactin surge during electroconvulsive therapy (ECT). The aim of this study is to review and meta-analyze data on ECT-related prolactin changes. METHOD: A systematic review and meta-analysis was conducted for trials investigating prolactin changes in ECT-treated patients using standard mean differences (SMD, 95% confidence intervals). Subgroup analyses included comparisons of ECT-related prolactin changes in women vs. men, patients receiving different anesthetics, bilateral vs. unilateral and high-vs. low-dose ECT. RESULTS: In six trials including 109 ECT-treated patients and 74 controls, prolactin changes were larger in ECT-treated patients than in controls (SMD = 0.89, 95%CI = 0.55, 1.23, p < 0.001 and 1.03, 95%CI = 0.31, 1.75, p = 0.005 for the fixed and random-effect model respectively), despite heterogeneity in the samples (I2 = 72%, τ2 = 0.62). Effects were led by differences in patients premedicated with methohexital (SMD = 1.14, 95%CI = 0.7, 1.57, p < 0.001 for both fixed and random-effect model). A meta-regression reported significant age effects (coefficient estimate 2.32, 95%CI = -0.73, 3.91, p < 0.01). Additionally, prolactin changes were larger in ECT-treated women than men (SMD = 0.88, 95%CI = 0.58, 1.18, p < 0.001 and 0.99, 95%CI = 0.22, 1.75, p = 0.012 for the fixed and random effect model). Bilateral ECT-treated patients had larger increase than unilateral ECT-treated patients (SMD = -0.81, 95%CI = -1.35, -0.27, p = 0.003 and -0.86, 95%CI = -1.46, -0.25, p = 0.006 for the fixed and random-effect model). Comparisons between high- and low-dose ECT-treated patients could not be conducted. The quality of the studies was overall poor, with four exceptions. DISCUSSION: Patients receiving ECT had larger prolactin increases than controls. Increases were larger in methohexital-premedicated patients, women vs. men and patients with bilateral vs. unilateral ECT.

Structural changes induced by electroconvulsive therapy are associated with clinical outcome.

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment option for major depressive disorder, so understanding whether its clinical effect relates to structural brain changes is vital for current and future antidepressant research. OBJECTIVE: To determine whether clinical response to ECT is related to structural volumetric changes in the brain as measured by structural magnetic resonance imaging (MRI) and, if so, which regions are related to this clinical effect. We also determine whether a similar model can be used to identify regions associated with electrode placement (unilateral versus bilateral ECT). METHODS: Longitudinal MRI and clinical data (Hamilton Depression Rating Scale) was collected from 10 sites as part of the Global ECT-MRI research collaboration (GEMRIC). From 192 subjects, relative changes in 80 (sub)cortical areas were used as potential features for classifying treatment response. We used recursive feature elimination to extract relevant features, which were subsequently used to train a linear classifier. As a validation, the same was done for electrode placement. We report accuracy as well as the structural coefficients of regions included in the discriminative spatial patterns obtained. RESULTS: A pattern of structural changes in cortical midline, striatal and lateral prefrontal areas discriminates responders from non-responders (75% accuracy, p < 0.001) while left-sided mediotemporal changes discriminate unilateral from bilateral electrode placement (81% accuracy, p < 0.001). CONCLUSIONS: The identification of a multivariate discriminative pattern shows that structural change is relevant for clinical response to ECT, but this pattern does not include mediotemporal regions that have been the focus of electroconvulsive therapy research so far.

Neurocognitive Effects of Combined Electroconvulsive Therapy (ECT) and Venlafaxine in Geriatric Depression: Phase 1 of the PRIDE Study.

OBJECTIVE: There is limited information regarding the tolerability of electroconvulsive therapy (ECT) combined with pharmacotherapy in elderly adults with major depressive disorder (MDD). Addressing this gap, we report acute neurocognitive outcomes from Phase 1 of the Prolonging Remission in Depressed Elderly (PRIDE) study. METHODS: Elderly adults (age ≥60) with MDD received an acute course of 6 times seizure threshold right unilateral ultrabrief pulse (RUL-UB) ECT. Venlafaxine was initiated during the first treatment week and continued throughout the study. A comprehensive neurocognitive battery was administered at baseline and 72 hours following the last ECT session. Statistical significance was defined as a two-sided p-value of less than 0.05. RESULTS: A total of 240 elderly adults were enrolled. Neurocognitive performance acutely declined post ECT on measures of psychomotor and verbal processing speed, autobiographical memory consistency, short-term verbal recall and recognition of learned words, phonemic fluency, and complex visual scanning/cognitive flexibility. The magnitude of change from baseline to end for most neurocognitive measures was modest. CONCLUSION: This is the first study to characterize the neurocognitive effects of combined RUL-UB ECT and venlafaxine in elderly adults with MDD and provides new evidence for the tolerability of RUL-UB ECT in an elderly sample. Of the cognitive domains assessed, only phonemic fluency, complex visual scanning, and cognitive flexibility qualitatively declined from low average to mildly impaired. While some acute changes in neurocognitive performance were statistically significant, the majority of the indices as based on the effect sizes remained relatively stable.