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.
CONCLUSIONS: 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.

Background and Objectives: Options for treatment-resistant bipolar depression (TRBPD) are limited. Electroconvulsive therapy (ECT) has shown efficacy in TRBPD. However, the cognitive deficits and memory concerns associated with ECT are problematic for a significant number of patients. It remains unclear what the next step is for patients with TRBPD who fail ECT. Materials and Methods: In this case report, we present a patient with TRBPD who sequentially received 12 sessions of brief-pulse right unilateral ECT, 22 sessions of ketamine infusion at 0.5-0.75 mg/kg for 40 min, and 39 sessions of deep repetitive transcranial magnetic stimulation (dTMS). Results: The patient had some benefit from ECT, but declined continuation of ECT due to memory concerns. The patient tolerated ketamine infusion well but had limited benefit. However, the patient responded well to acute treatment with dTMS and maintained relative stability for more than 2 years. Conclusions: This case suggests that patients with TRBPD who fail ECT and/or ketamine infusion might benefit from dTMS.

UNASSIGNED: 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.
UNASSIGNED: To evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT.
UNASSIGNED: 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.
UNASSIGNED: Eligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

BACKGROUND: Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia.
METHODS: We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel-Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach.
CONCLUSIONS: Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients.
BACKGROUND: PROSPERO-ID CRD42023410645.

Background: Attachment-based interventions have been extensively studied in neurotypical patient populations. In neurodivergent patient populations, however, emphasis on and current research into attachment-based interventions are centered on early childhood. Minimal research has been conducted in school-aged children with autism spectrum disorder (ASD), and even less research has focused on attachment-based interventions for children with significant comorbidities such as catatonia. Case Report: We present the case of a 12-year-old female that involved dyadic work in conjunction with biologic interventions for the treatment of ASD and catatonia. Psychosocial interventions were centered on an attachment-based framework and behavioral skills training that incorporated elements of parent management training. We observed and tracked the patient\'s uncooperativeness, underproductive speech, emotional withdrawal, and anxiety via the Brief Psychiatric Rating Scale for Children. Attachment- and behavioral-based interventions in conjunction with psychotropic medications and electroconvulsive therapy resulted in improvements. Conclusion: This case illustrates the potential advantages that attachment- and behavioral-based psychotherapeutic interventions can confer in complex cases involving neurodivergent patients. The case also highlights the lack of current research into and understanding of attachment theory in children and adolescents with ASD. Research is needed into the role of attachment-based interventions in patients with ASD and other psychiatric comorbidities, particularly in patient populations beyond preschool age. Initiating nonbiologic interventions in conjunction with biologic interventions may also enhance outcomes and warrants further investigation.

The aim of this short narrative review was to evaluate the existing literature regarding the clinical use of ketamine among individuals with dementia, especially those with behavioral disturbances. PubMed, Cochrane, and Ovid (Embase, APA PsycINFO, and MEDLINE) databases were searched for abstracts using the search terms \"ketamine\" AND \"dementia.\" Only articles describing the use of ketamine in individuals with dementia were included. Articles that did not include individuals with dementia, did not use ketamine, were published in a non-English language, primarily described animal studies, or were reviews were excluded. Three case reports met the inclusion criteria. One described the use of subcutaneous ketamine for depression, one described the use of intramuscular ketamine for acute agitation, and one described the use of S-ketamine as anesthesia during electroconvulsive therapy for depression and catatonia. No significant adverse effects were reported in any of the cases. Although the use of ketamine in the treatment of depression and agitation associated with dementia has potential, the current evidence remains limited. High-quality prospective studies are needed to confirm the observations of these case reports before ketamine can be used to treat behavioral disturbances in individuals with dementia.

UNASSIGNED: Electroconvulsive therapy (ECT) is an effective intervention for psychiatric patients. Succinylcholine is considered the drug of choice for muscle relaxation for ECT. Significant adverse effects of succinylcholine include fasciculation and myalgia. Dexmedetomidine is a highly selective α-2 adrenergic agonist. This study aims to determine the efficacy of a low dose of dexmedetomidine in reducing succinylcholine-induced myalgia in patients receiving ECT.
UNASSIGNED: This randomised controlled trial was conducted on 100 patients, aged 18-65 years, undergoing ECT, who were randomly allocated into two groups with an allocation ratio of 1:1. Group D received intravenous (IV) dexmedetomidine 0.25 µg/kg, and Group C received IV normal saline (0.9%). Patients\' self-reported myalgia scores were measured after 60 min of the procedure. Fasciculations were noted after IV succinylcholine administration. Heart rate (HR) and mean blood pressure (MBP) were measured at baseline, after infusion (5 min) and after ECT (0, 2.5, 5, 10, 15, 30 min). Continuous data were analysed using a Student\'s t-test for two-group comparisons, a mixed model analysis of variance for group comparisons and various time point analyses. Categorical data were analysed using the Chi-square/Fisher\'s exact test.
UNASSIGNED: There were no differences between the groups regarding demographics. Myalgia and fasciculations were less in Group D than in Group C (P < 0.001). MBP and HR changes were comparable (P > 0.05).
UNASSIGNED: A low dose of dexmedetomidine (0.25 µg/kg) effectively reduces myalgia and fasciculations due to succinylcholine in patients undergoing electroconvulsive therapy.

BACKGROUND: Numerous studies show that electroconvulsive therapy (ECT) induces hippocampal neuroplasticity, but findings are inconsistent regarding its clinical relevance. This study aims to investigate ECT-induced plasticity of anterior and posterior hippocampi using mathematical complexity measures in neuroimaging, namely Higuchi\'s fractal dimension (HFD) for fMRI time series and the fractal dimension of cortical morphology (FD-CM). Furthermore, we explore the potential of these complexity measures to predict ECT treatment response.
METHODS: Twenty patients with a current depressive episode (16 with major depressive disorder and 4 with bipolar disorder) underwent MRI-scans before and after an ECT-series. Twenty healthy controls matched for age and sex were also scanned twice for comparison purposes. Resting-state fMRI data were processed, and HFD was computed for anterior and posterior hippocampi. Group-by-time effects for HFD in anterior and posterior hippocampi were calculated and correlations between HFD changes and improvement in depression severity were examined. For FD-CM analyses, we preprocessed structural MRI with CAT12\'s surface-based methods. We explored group-by-time effects for FD-CM and the predictive value of baseline HFD and FD-CM for treatment outcome.
RESULTS: Patients exhibited a significant increase in bilateral hippocampal HFD from baseline to follow-up scans. Right anterior hippocampal HFD increase was associated with reductions in depression severity. We found no group differences and group-by-time effects in FD-CM. After applying a whole-brain regression analysis, we found that baseline FD-CM in the left temporal pole predicted reduction of overall depression severity after ECT. Baseline hippocampal HFD did not predict treatment outcome.
CONCLUSIONS: This study suggests that HFD and FD-CM are promising imaging markers to investigate ECT-induced neuroplasticity associated with treatment response.

BACKGROUND: Psychotic bipolar depression (PBD) is a prevalent yet understudied psychiatric illness, and there are no specific guidelines or Food and Drug Administration-approved medications for its treatment. Recent studies suggest that some antipsychotics and mood stabilizers may be effective in managing bipolar depression; however, their effectiveness for PBD remains unclear. Given the urgent need for more focused research for managing PBD, we conducted a literature review to summarize the existing literature on PBD.
METHODS: We conducted an electronic literature search from the 1960s to 2023, utilizing PubMed, MEDLINE, EMBASE, and Google, and selected studies based on their relevance to PBD.
RESULTS: PBD is a complex disorder, with 50%-75% of patients with bipolar disorder exhibiting psychotic features. This likelihood increases among those with a history of psychotic mania. Treatment guidelines often recommend a combination of mood stabilizers, antipsychotics, or electroconvulsive therapy, but they do not specify a first-line treatment. PBD symptoms can be masked by mixed high mood and energy feelings, potentially delaying diagnosis and treatment while increasing suicide risk. Limited research has evaluated outcomes of various treatments for PBD, and despite the lack of evidence for superior efficacy, in clinical practice, antipsychotics are frequently prescribed. Notably, combining an antipsychotic with selective noradrenaline reuptake inhibitors or tricyclic antidepressants may be effective, but including a mood stabilizer is necessary.
CONCLUSIONS: PBD poses a significant challenge in mental health due to its severity and the lack of consensus on optimal treatment approaches. There is a critical need for more dedicated clinical trials and research to answer key questions about the effective treatment of acute PBD, ideal follow-up care, traits of responders to different therapies, and decision models for subsequent treatments.

Transnasal humidified rapid-insufflation ventilator exchange (THRIVE) has been reported to have better efficacy during anesthesia induction compared to conventional mask ventilation, including improved oxygenation and prolonged safe apnea time. This study reports on the effectiveness of the THRIVE system during modified electroconvulsive therapy (mECT) for a patient experiencing severe hypoxia. A 78-year-old female patient with bipolar disorder received maintenance mECT every four weeks. She previously experienced a significant hypoxic event, with oxygen saturation (SpO2) dropping to 50% following electrical stimulation. In response, we employed the THRIVE system, designed to deliver high-flow, 100% oxygen, thereby extending apnea tolerance. The implementation of THRIVE ensured a stable oxygen supply, maintaining oxygen saturation levels above 95% throughout the mECT procedure. THRIVE is useful for treating hypoxia that occurs due to the unavoidable lack of ventilation during mECT.