Adherence to clinical practice guidelines for using electroconvulsive therapy in elderly depressive patients.

OBJECTIVES: Electroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines. METHODS: In this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. RESULTS: We identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT. CONCLUSION: Even if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long.

Unraveling epigenomic signatures and effectiveness of electroconvulsive therapy in treatment-resistant depression patients: a prospective longitudinal study.

BACKGROUND: Electroconvulsive therapy (ECT) benefits patients with treatment-resistant depression (TRD), but the underlying biological processes are unclear. We conducted an epigenome-wide association study in 32 TRD patients undergoing ECT to depict ECT-associated methylation changes. Illness severity and ECT outcomes were assessed with the Montgomery-Åsberg Depression Rating Scale at baseline (T0) and 1 month after its end (T1). Methylation was profiled at T0 and T1 with the Illumina Infinium Methylation EPIC BeadChip array. RESULTS: Longitudinal T0-T1 analyses showed 3 differentially methylated probes (DMPs) with nominal p values ≤ 10-5, with 2 annotated in the genes CYB5B and PVRL4. Including covariates, we found 4 DMPs for symptoms variation, annotated in FAM20C, EPB41, OTUB1 and ADARB1, and 3 DMPs for response status, with 2 annotated in IQCE and FAM20C. Regional analysis revealed 54 differentially methylated regions (DMRs) with nominal p value area ≤ 0.05, with 9 presenting adjusted p-value area ≤ 0.10, annotated in MCF2L, SLC25A24, RUNX3, MIR637, FOXK2, FAM180B, POU6F1, ALS2CL and CCRL2. Considering covariates, we found 21 DMRs for symptoms variation and 26 DMRs for response (nominal p value area ≤ 0.05), with 4 presenting adjusted p-value area ≤ 0.10 for response, annotated in SNORD34, NLRP6, GALNT2 and SFT2D3. None remained significant after false discovery rate correction. Notably, ADARB1 variants are associated with suicide attempt in patients with psychiatric disorders, and SLC25A24 relates to conduct disorder. Several DMPs and DMRs are annotated in genes associated with inflammatory/immune processes. Longitudinal analyses on females (n = 22) revealed statistically significant DMRs (adjusted p value area ≤ 0.05) and trend-significant DMRs (adjusted p value area ≤ 0.07) for symptoms variation and response status, annotated in genes related to psychiatric disorders (ZFP57, POLD4, TRIM10, GAS7, ADORA2A, TOLLIP), trauma exposure (RIPOR2) and inflammatory/immune responses (LAT, DLX4, POLD4, FAM30A, H19). Pathway analysis on females revealed enrichment for transcriptional activity, growth factors, DNA maintenance, and immune pathways including IRF7 and IRF2. CONCLUSION: Although no significant results were found for the whole cohort, the study provides insights into ECT-associated methylation changes, highlighting DMPs and DMRs related to ECT outcomes. Analyses on females revealed significant DMRs and pathways related to psychiatric disorders and inflammatory/immune processes.

Catatonia.

Catatonia is a neuropsychiatric disorder characterized by motor, affective and cognitive-behavioural signs, which lasts from hours to days. Intensive research over the past two decades has led to catatonia being recognized as an independent diagnosis in the International Classification of Diseases, 11th Revision (ICD-11) since 2022. Catatonia is found in 5-18% of inpatients on psychiatric units and 3.3% of inpatients on medical units. However, in an unknown number of patients, catatonia remains unrecognized and these patients are at risk of life-threatening complications. Hence, recognizing the symptoms of catatonia early is crucial to initiate appropriate treatment to achieve a favourable outcome. Benzodiazepines such as lorazepam and diazepam, electroconvulsive therapy, and N-methyl-D-aspartate antagonists such as amantadine and memantine, are the cornerstones of catatonia therapy. In addition, dopamine-modulating second-generation antipsychotics (for example, clozapine and aripiprazole) are effective in some patient populations. Early and appropriate treatment combined with new screening assessments has the potential to reduce the high morbidity and mortality associated with catatonia in psychiatric and non-psychiatric settings.

Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression: A Secondary Analysis of a Randomized Clinical Trial.

Importance: 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. Objective: To evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT. Design, Setting, and Participants: 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. Exposures: Eligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.

Caution for psychiatrists: malignant hyperthermia risks with the anesthetic agent succinylcholine (Suxamethonium) during electroconvulsive therapy.

BACKGROUND: Malignant hyperthermia is a potentially lethal condition triggered by specific anesthetic drugs, especially a depolarizing muscle relaxant of succinylcholine (Suxamethonium). Despite the frequent use of succinylcholine with electroconvulsive therapy (ECT), there has been no reported case of potentially lethal malignant hyperthermia following ECT. In addition, the time interval between the administration of succinylcholine and the onset of malignant hyperthermia has not been outlined in the context of ECT. CASE PRESENTATION: We present the case of a 79-year-old woman suffering from severe depression, who experienced severe malignant hyperthermia due to succinylcholine administration during an ECT session. She presented with a high fever of 40.2 °C, tachycardia of 140/min, hypertension with a blood pressure exceeding 200 mmHg, significant muscle rigidity, and impaired consciousness. These symptoms emerged two hours after ECT, which occurred in a psychiatric ward rather than an operating room, and reached their peak in less than 24 h. She was given 60 mg of dantrolene, which quickly reduced the muscular rigidity. Subsequently, she received two additional doses of 20 mg and 60 mg of dantrolene, which brought her fever down to 36.2 °C and completely eased her muscle rigidity within two days after ECT. CONCLUSIONS: This is the first reported case of potentially lethal malignant hyperthermia after ECT. In addition, it highlights the delayed onset of malignant hyperthermia following an ECT procedure, emphasizing the necessity for psychiatrists to recognize its onset even after the treatment. In the light of potentially lethal consequences of malignant hyperthermia, it is critically important for psychiatrists to closely monitor both intraoperative and postoperative patient's vital signs and characteristic physical presentations, promptly identify any symptomatic emergence, and treat it immediately with dantrolene.

Role of Electroconvulsive Therapy, Ketamine Infusion, and Deep Repetitive Transcranial Magnetic Stimulation in Treatment-Resistant Bipolar Depression: A Case Report.

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.

Electroconvulsive therapy in N-methyl-d-aspartate receptor encephalitis: A retrospective cohort and scoping review of literature.

Neuropsychiatric symptoms in N-methyl-d-aspartate receptor encephalitis (NMDARE) have led some to pursue empiric trials of electroconvulsive therapy (ECT). A scoping review identified 39 patients diagnosed with NMDARE undergoing ECT. Separately, a retrospective cohort was reviewed to characterize 21 patients. Clinical improvement was attributed to ECT in 49% of patients in the scoping review and 19% of patients in the retrospective cohort; timing of immunotherapies was a confounding factor. Worsening of clinical course following ECT was reported in 28% of patients in the scoping review and 38% of patient in the retrospective review. There is currently insufficient data supporting a beneficial effect of ECT in NMDARE.

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.

Is there evidence for using ketamine among individuals with dementia?

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.

Depression: Managing Resistance and Partial Response to Treatment.

Treatment-resistant depression is defined as absence of remission despite trials of two or more antidepressant medications and can occur in up to 31% of patients with major depressive disorder. Partial response to treatment is defined as less than 50% reduction in depression-rating scores. Before diagnosing treatment-resistant depression or partial response to treatment, adherence to adequate doses and duration of medications should be confirmed. Management strategies include adding psychotherapy, switching antidepressant medication class, or augmenting with additional medications. Current guidelines recommend augmentation with a second-generation antidepressant, an atypical antipsychotic, tricyclic antidepressants, lithium, or a triiodothyronine medication as pharmacologic options. Ketamine and esketamine can also be used as augmentation for treatment-resistant depression and may help reduce suicidal ideation. Electroconvulsive therapy and repetitive transcranial magnetic stimulation may be effective. Pharmacogenetic testing has limited evidence and is not recommended. Nonpharmacologic therapies include psychotherapy, exercise, and focused dietary changes.

Individual large-scale functional network mapping for major depressive disorder with electroconvulsive therapy.

Personalized functional connectivity mapping has been demonstrated to be promising in identifying underlying neurophysiological basis for brain disorders and treatment effects. Electroconvulsive therapy (ECT) has been proved to be an effective treatment for major depressive disorder (MDD) while its active mechanisms remain unclear. Here, 46 MDD patients before and after ECT as well as 46 demographically matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. A spatially regularized form of non-negative matrix factorization (NMF) was used to accurately identify functional networks (FNs) in individuals to map individual-level static and dynamic functional network connectivity (FNC) to reveal the underlying neurophysiological basis of therepetical effects of ECT for MDD. Moreover, these static and dynamic FNCs were used as features to predict the clinical treatment outcomes for MDD patients. We found that ECT could modulate both static and dynamic large-scale FNCs at individual level in MDD patients, and dynamic FNCs were closely associated with depression and anxiety symptoms. Importantly, we found that individual FNCs, particularly the individual dynamic FNCs could better predict the treatment outcomes of ECT suggesting that dynamic functional connectivity analysis may be better to link brain functional characteristics with clinical symptoms and treatment outcomes. Taken together, our findings provide new evidence for the active mechanisms and biomarkers for ECT to improve diagnostic accuracy and to guide individual treatment selection for MDD patients.

Response to electroconvulsive therapy in elderly patients with late-onset bipolar disorder: The impact of cerebral small vessel disease.

OBJECTIVES: Cerebral Small Vessel Disease (CSVD) is a chronic, progressive vascular disorder that confers increased vulnerability to psychiatric syndromes, including late-life mood disorders. In this study, we investigated the impact of CSVD on electroconvulsive therapy (ECT) outcomes in patients with late-onset bipolar disorder (BD). METHODS: A sample of 54 non-demented elderly patients (≥60 years) with late-onset BD and treatment-resistant major depression, mixed state, or catatonia who underwent bilateral ECT were included in this naturalistic observational study. A diagnosis of CSVD was established based on brain neuroimaging performed before ECT. All patients were evaluated before and after ECT using the Brief Psychiatric Rating Scale (BPRS), the Hamilton Rating Scale for Depression (HAM-D), and the Clinical Global Impression scale (CGI). RESULTS: Of the total sample, 19 patients were diagnosed with CSVD (35.2%). No significant differences were observed at baseline between patients with and without CSVD. Overall, a response was obtained in 66%-68.5% of patients, with remission in 56.2%. No significant differences in ECT outcomes were found between those with and without CSVD, and both groups exhibited substantial improvements in symptom severity following ECT. CONCLUSIONS: The outcome of ECT in late-onset BD was not influenced by the presence of CSVD. This finding aligns with previous research on unipolar depression. Accordingly, ECT should be considered for elderly patients with late-onset BD, regardless of the presence of CSVD.

Magnetic Seizure Therapy vs Modified Electroconvulsive Therapy in Patients With Bipolar Mania: A Randomized Clinical Trial.

Importance: Bipolar mania is a common disabling illness. Electroconvulsive therapy (ECT) is an effective treatment for patients with severe mania, though it is limited by the risk of cognitive adverse effects. Magnetic seizure therapy (MST) as an alternative treatment to ECT for bipolar mania has not yet been reported. Objective: To compare the effectiveness and cognitive adverse effects of MST and ECT in bipolar mania. Design, Setting, and Participants: This randomized clinical trial was conducted at the Shanghai Mental Health Center from July 1, 2017, through April 26, 2021. Forty-eight patients with bipolar mania were recruited and randomly allocated to receive MST or ECT. The data analysis was performed from June 5, 2021, through August 30, 2023. Interventions: Patients completed 2 or 3 sessions of MST or ECT per week for a total of 8 to 10 sessions. The MST was delivered at 100% device output with a frequency of 75 Hz over the vertex. Main Outcomes and Measures: The primary outcomes were reduction of total Young Manic Rating Scale (YMRS) score and response rate (more than 50% reduction of the total YMRS score compared with baseline). An intention-to-treat (ITT) analysis and repeated-measures analyses of variance were conducted for the primary outcomes. Results: Twenty patients in the ECT group (mean [SD] age, 31.6 [8.6] years; 12 male [60.0%]) and 22 patients in the MST group (mean [SD] age, 34.8 [9.8] years; 15 male [68.2%]) were included in the ITT analysis. The response rates were 95.0% (95% CI, 85.4%-100%) in the ECT group and 86.4% (95% CI, 72.1%-100%) in the MST group. The YMRS reduction rate (z = -0.82; 95% CI, -0.05 to 0.10; P = .41) and response rate (χ2 = 0.18; 95% CI, -0.13 to 0.31; P = .67) were not significantly different between the groups. The time-by-group interaction was significant for the language domain (F1,24 = 7.17; P = .01), which was well preserved in patients receiving MST but worsened in patients receiving ECT. No serious adverse effects were reported in either group. Conclusions and Relevance: These findings suggest that MST is associated with a high response rate and fewer cognitive impairments in bipolar mania and that it might be an alternative therapy for the treatment of bipolar mania. Trial Registration: ClinicalTrials.gov Identifier: NCT03160664.