Electroconvulsive therapy for the acute management of severe agitation in dementia (ECT-AD): A modified study protocol.

OBJECTIVE: This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe treatment-refractory agitation in advanced dementia. The aims are to assess agitation reduction using the Cohen-Mansfield Agitation Inventory (CMAI), evaluate tolerability and safety outcomes, and explore the long-term stability of agitation reduction and global functioning. Due to challenges encountered during implementation, including recruitment obstacles and operational difficulties, the study design was modified to an open-label format and other protocol amendments were implemented. METHODS: Initially, the RCT randomized participants 1:1 to either ECT plus usual care or simulated ECT plus usual care (S-ECT) groups. As patients were enrolled, data were collected from both ECT and simulated ECT (S-ECT) patients. The study now continues in an open-label study design where all patients receive actual ECT, reducing the targeted sample size from 200 to 50 participants. RESULTS: Study is ongoing and open to enrollment. CONCLUSION: The transition of the ECT-AD study design from an RCT to open-label design exemplifies adaptive research methodologies in response to real-world challenges. Data from both the RCT and open-label phases of the study will provide a unique perspective on the role of ECT in managing severe treatment-refractory agitation in dementia, potentially influencing future clinical practices and research approaches.

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.

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 Impact of COVID-19 on Brain Stimulation Therapy.

Among the far-reaching effects of the COVID-19 pandemic has been restricted access to safe and effective forms of psychiatric treatment. Focusing on electroconvulsive therapy and transcranial magnetic stimulation, we review the pandemic's impact on brain stimulation therapy by asking 3 fundamental questions-Where have we been? How are we doing? And where are we going?

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.

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.

Electric field causes volumetric changes in the human brain.

Recent longitudinal neuroimaging studies in patients with electroconvulsive therapy (ECT) suggest local effects of electric stimulation (lateralized) occur in tandem with global seizure activity (generalized). We used electric field (EF) modeling in 151 ECT treated patients with depression to determine the regional relationships between EF, unbiased longitudinal volume change, and antidepressant response across 85 brain regions. The majority of regional volumes increased significantly, and volumetric changes correlated with regional electric field (t = 3.77, df = 83, r = 0.38, p=0.0003). After controlling for nuisance variables (age, treatment number, and study site), we identified two regions (left amygdala and left hippocampus) with a strong relationship between EF and volume change (FDR corrected p<0.01). However, neither structural volume changes nor electric field was associated with antidepressant response. In summary, we showed that high electrical fields are strongly associated with robust volume changes in a dose-dependent fashion.

Electroconvulsive Therapy Augmentation in Clozapine-Resistant Schizophrenia: A Prospective, Randomized Study.

(Reprinted with permission from Am J Psychiatry 2015; 172:52-58).

Electroconvulsive therapy (ECT) in schizophrenia: a review of recent literature.

PURPOSE OF REVIEW: ECT remains an important, yet underutilized, treatment for schizophrenia. Recent research shows that medication-resistant patients with schizophrenia, including those resistant to clozapine, respond well to ECT augmentation. The purpose of this article is to review recent studies of the use of ECT in the treatment of schizophrenia. RECENT FINDINGS: We performed an electronic database search for articles on ECT and schizophrenia, published in 2017. The main themes of these articles are: epidemiological data on ECT use from various countries; retrospective studies, prospective studies and meta-analyses focusing on efficacy and cognitive side-effects of ECT in schizophrenia; ECT technical parameters and potential biomarkers. SUMMARY: There is growing evidence to support the use of ECT for augmentation of antipsychotic response in the treatment of schizophrenia. Cognitive side-effects are generally mild and transient. In fact, many studies show improvement in cognition, possibly related to the improvement in symptoms. There is wide variation among countries in the use of ECT for the treatment of schizophrenia. There are also variations in the choice of ECT electrode placement, parameters and schedules. These technical differences are likely minor and should not interfere with the treatment being offered to patients. Further, long-term studies are needed to optimize ECT treatment parameters, to examine the effect of maintenance ECT and to investigate neuroimaging/biomarkers to understand the mechanism of action and identify potential response predictors to ECT.

Characteristics of Patients Involved in Physical Assault in an Acute Inpatient Psychiatric Setting.

BACKGROUND: Although aggressive behavior in psychiatric settings is a major concern, very few studies have focused exclusively on physical assault in a general inpatient psychiatric population. OBJECTIVES: This study had 3 main goals: (1) to evaluate the prevalence of assaultive behavior in an acute psychiatric hospital; (2) to identify the clinical and socio-demographic factors associated with assaultive behavior during hospitalization; and (3) to explore whether a diagnosis of schizophrenia spectrum disorder increases the risk of assaultive behavior. METHODS: We conducted a retrospective chart review of patients admitted to acute units in a psychiatric hospital between 2009 and 2012. A subset of occurrence reports identified by a multidisciplinary team as "physical assault" was included in the analysis. Using logistic multivariate regression analysis, these patients were compared with a randomly selected nonassaultive control group, matched for length of stay to identify factors associated with assaultive behavior. RESULTS: Of 757 occurrence reports, 613 met criteria for significant assault committed by 356 patients over 309,552 patient days. The assault incident density was 1.98 per 1000 patient days. In the logistic regression model of best fit, the factors significantly associated with assaultive behavior were age, legal status, and substance use. A diagnosis of schizophrenia spectrum disorder was not significantly associated with assaultive behavior. CONCLUSIONS: Clinicians should take extra precautions for involuntarily admitted young patients with a history of substance use, as they are more likely to exhibit assaultive behavior. A diagnosis of schizophrenia spectrum disorder in itself is not significantly associated with assaultive behavior. Screening instruments such as the Dynamic Appraisal of Situational Aggression may be useful in assessing risk of assault.

Indications for and use of long-acting injectable antipsychotics: consideration from an inpatient setting.

Studies have examined the differences in sociodemographic/clinical characteristics between patients on long-acting injectable (LAI) versus oral medications. However, most studies did not focus specifically on patients for whom LAIs would clearly be indicated. We performed a chart review of patients with schizophrenia or schizoaffective disorder. Patients were categorized as having an 'indication for an LAI' or not on the basis of their adherence history. Patients for whom an LAI was indicated and prescribed on discharge were then compared with similar patients for whom an LAI was not prescribed. Of 305 charts reviewed, consisting of 279 unique patients, 27.2% were judged to have an indication for an LAI (n=76), but only 32.9% of these (n=25) were discharged on an LAI. In the multiregression model, being African American, residing in a psychiatric residence, having a previous history of an LAI trial, and being treated with a higher antipsychotic dose were predictive of LAI prescription. It is important to focus on the population who are not likely to receive an LAI, but who have such indications for treatment.

Electroconvulsive therapy augmentation in clozapine-resistant schizophrenia: a prospective, randomized study.

OBJECTIVE: Up to 70% of patients with treatment-resistant schizophrenia do not respond to clozapine. Pharmacological augmentation to clozapine has been studied with unimpressive results. The authors examined the use of ECT as an augmentation to clozapine for treatment-refractory schizophrenia. METHOD: In a randomized single-blind 8-week study, patients with clozapine-resistant schizophrenia were assigned to treatment as usual (clozapine group) or a course of bilateral ECT plus clozapine (ECT plus clozapine group). Nonresponders from the clozapine group received an 8-week open trial of ECT (crossover phase). ECT was performed three times per week for the first 4 weeks and twice weekly for the last 4 weeks. Clozapine dosages remained constant. Response was defined as ≥40% reduction in symptoms based on the psychotic symptom subscale of the Brief Psychiatric Rating Scale, a Clinical Global Impressions (CGI)-severity rating <3, and a CGI-improvement rating ≤2. RESULTS: The intent-to-treat sample included 39 participants (ECT plus clozapine group, N=20; clozapine group, N=19). All 19 patients from the clozapine group received ECT in the crossover phase. Fifty percent of the ECT plus clozapine patients met the response criterion. None of the patients in the clozapine group met the criterion. In the crossover phase, response was 47%. There were no discernible differences between groups on global cognition. Two patients required the postponement of an ECT session because of mild confusion. CONCLUSIONS: The augmentation of clozapine with ECT is a safe and effective treatment option. Further research is required to determine the persistence of the improvement and the potential need for maintenance treatments.