The influence of concomitant antidepressant and antipsychotic medication on antidepressant effect and seizure duration of electroconvulsive therapy.

Background: A significant proportion of patients with a depressive disorder show resistance to pharmacological and psychotherapeutic antidepressant treatments. Electroconvulsive therapy (ECT) is still one of the most effective treatment methods, especially in the acute phase. In everyday clinical practice, this usually accompanies pharmacological treatment. It has been shown that pharmacological treatment following acute ECT treatment reduces the rate of relapses. However, the effect of various antidepressants (ADs) and antipsychotics (APs) on the effect during the course of ECT has rarely been investigated. Methods: In this retrospective chart review study, the data of 104 depressive patients treated with ECT were examined. We analyzed the influence of concomitant administration of AD and AP or no psychotropic medication on the effect of ECT using the Montgomery-Åsberg Depression Rating Scale (MADRS). We further analyzed the influence of the ADs Bupropion, Venlafaxine, and Sertraline or no AD and the influence of augmentation with Aripiprazole or Quetiapine or Olanzapine. Results/discussion: Psychotropic medication did not have an impact on antidepressant efficacy of ECT as measured with the MADRS scores. In addition, the comparison between the antidepressant or antipsychotic medications themselves did not show any significant difference. However, we found a significantly different seizure duration depending on the antidepressant substance that patients received during ECT (p = .008). ECT treatment itself led to a highly significant reduction of 13.3 points in the MADRS (p <.001). Conclusion: Taken together, our study underlines that concomitant psychotropic medication while doing electroconvulsive therapy does not bare the risk of prolonged seizure duration or does it reduce the effectiveness of ECT. To the best of our knowledge, this study is the first to examine the effect of treatment with antidepressants in combination with antipsychotics while doing ECT. In light of our results, this combination therapy is safe and effective. Bearing in mind the delay in onset of antidepressant action of medication and the importance of antidepressant medication for relapse prevention, this study further supports the recommendation that psychotropic medication should be given in adjunction to ECT.

Catatonia in patients with dementia: A descriptive study of clinical profiles and treatment response.

BACKGROUND: Catatonia is a highly prevalent syndrome in patients presenting with major neurocognitive disorders (dementia). In this study, we aim to provide a comprehensive description of the clinical and therapeutic aspects of catatonia in patients with dementia. METHOD: This descriptive study, conducted between September 2015 and June 2022, collected data from 25 patients diagnosed with dementia, out of 143 patients treated for catatonia in our specialized psychiatry department. We collected sociodemographic, clinical and treatment data for each patient. RESULTS: Dementia patients constituted 17% of the catatonic cases. Predominantly female, the cohort had a mean age of 65. Diagnoses included Alzheimer's (4 patients, 17%) and Parkinson's (1 patient, 4%) diseases, Lewy body dementia (5 patients, 21%), vascular dementia (4 patients, 17%) and frontotemporal lobar degeneration (10 patients, 41%). The mean Bush-Francis Catatonia Rating Scale score upon admission was 20/69. Overall, complete remission of catatonia was achieved in 75% of patients (n=18), with only 13% (n=3) responding to lorazepam alone, while others required additional interventions such as electroconvulsive therapy (ECT) and/or amantadine. Vascular dementia was predominantly observed in cases resistant to treatment. CONCLUSION: The findings indicate a frequent co-occurrence of catatonia and dementia, highlighting treatability yet suggesting a potential for resistance to lorazepam, which varies by dementia diagnosis. Investigating the mechanisms underlying this resistance and the variability in treatment response is crucial for developing more precise therapeutic strategies.

Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: A RECOVER trial report.

BACKGROUND: RECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention. OBJECTIVE: To describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine. METHODS: Medical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) versus not qualified (N = 228) for RECOVER, and among the qualified group as a function of exposure to INTs during the current major depressive episode (MDE). RESULTS: Unipolar MDD patients who qualified for RECOVER had marked TRD (median of 11.0 lifetime failed antidepressant treatments), severe disability (median WHODAS score of 50.0), and high rate of baseline suicidality (77% suicidal ideation, 40% previous suicide attempts). Overall, 71% had received at least one INT. Compared to the no INT group, INT recipients were younger and more severely depressed (QIDS-C, QIDS-SR), had greater suicidal ideation, earlier diagnosis of MDD, and failed more antidepressant medication trials. CONCLUSIONS: RECOVER-qualified unipolar patients had marked TRD and marked treatment resistance with most failing one or more prior INTs. Treatment with ≥1 INTs in the current MDE was associated with earlier age of MDD onset, more severe clinical presentation, and greater treatment resistance relative to patients without a history of INT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03887715.

Data on electroconvulsive seizure in mice, effects of anesthesia on immediate early gene expression.

Although electroconvulsive therapy (ECT) is one of the most effective treatments for severe mood and psychotic disorders, the mechanisms underlying its therapeutic effects remain unknown. Electroconvulsive stimulation (ECS), the animal model for ECT, can be used to investigate the potential therapeutic mechanisms of ECT in rodents. ECS produces numerous effects in the brain, such as increasing levels of growth factors, inducing dendritic sprouting, and stimulating neurogenesis. It also induces high-level expression of immediate early genes (IEGs) that have been implicated in the pathogenesis of schizophrenia, such as early growth response 3 (Egr3) and activity-regulated cytoskeleton-associated protein (Arc), a validated downstream target of Egr3 [1-3]. However, the effect of isoflurane anesthesia preceding ECS on IEG response in mice has not been well characterized. This article provides immunofluorescent data of the activity responsive IEG ARC in the dorsal and ventral dentate gyrus of wildtype (WT) mice following ECS with or without anesthesia, as well as following sham ECS. The data in this article relate to a published article that employed serial ECS in mice to investigate the requirement of Egr3 in the neurobiological effects of this model of ECT [4]. The ability to study the effects of serial ECS has been limited in mice due to high rates of mortality during seizure. Administration of isoflurane anesthesia prior to ECS significantly reduces rodent mortality, irrespective of the number of times ECS is applied [5]. Since general anesthesia is administered to patients prior to ECT, use of isoflurane prior to ECS also more closely models the clinical use of ECT [6].

Association between electroconvulsive therapy and time to readmission after a manic episode.

OBJECTIVE: The majority of patients hospitalized for treatment of a manic episode are readmitted within 2 years despite maintenance treatment. Electroconvulsive therapy (ECT) has been associated with lower rehospitalization rates in some psychiatric conditions, but its association with readmission after a manic episode has not been investigated. Therefore, the aim of this study was to determine whether the time to readmission in patients with mania treated with ECT was longer than in patients not treated with ECT and whether there were subgroups of patients that benefited more. METHODS: This was a nationwide register-based, observational study. All patients diagnosed with bipolar disorder, manic episode, admitted to any hospital in Sweden between 2012 and 2021 were included. Patients contributed data to the study for every admission. All admissions were followed up until psychiatric readmission, death, or the end of the study (December 31, 2021). Association between ECT and time to readmission was analyzed. A paired samples model was performed for 377 patients with at least two admissions for mania, treated with ECT at one admission and without ECT at the other admission. Times to readmission were analyzed. RESULTS: A total of 12,337 admissions were included; mean (SD) age 47.7 (17.2), 5443 (44.1%) men. Readmission rate within 1 year was 54.6%. ECT was administered in 902 (7.3%) admissions. Within 30 days after admission, 182 out of 894 (20.4%) patients treated with ECT versus 2105 out of 11,305 (18.6%) patients treated without ECT were readmitted. There was no association between ECT and time to readmission (aHR 1.00, 95% CI 0.86-1.16, p = 0.992) in the model with all admissions. The paired samples model included 754 admissions (377 patients), mean (SD) age during admission without ECT was 45.6 (16.5), and with ECT 46.6 (16.4), 147 (39.0%) were men. In that model, readmission rate within 30 days for treatment with ECT was 19.0%, and for treatments without ECT, 24.1% (aHR 0.75, 95% CI 0.55-1.02, p = 0.067). CONCLUSION: Readmission rates after inpatient treatment of mania were high. ECT was not significantly associated with longer time to readmission, but there was a trend toward a protective effect of ECT when admissions with and without ECT were compared within the same patients.

Perspectives in treatment-resistant depression: esketamine and electroconvulsive therapy.

Modern electroconvulsive therapy (ECT) and the approval of nasal esketamine for clinical use have significantly improved the approach to treatment-resistant depression (TRD), which is defined as non-response to at least two different courses of antidepressants with verified adherence to treatment, adequate dosage, and duration of treatment. The goal of this literature review is to present the newest evidence regarding efficacy and safety. Furthermore, we aim to provide an overview of future perspectives in this field of research, for example, regarding structural and molecular effects. Both treatment methods will be critically evaluated for their individual advantages, disadvantages, and response rates. Firstly, we will discuss the well-established method of ECT and its different treatment modalities. Secondly, we will discuss the properties of ketamine, the discovery of its antidepressive effects and the route to clinical approval of the esketamine nasal spray. We will comment on research settings which have evaluated intravenous ketamine against ECT. The decision-making process between esketamine nasal spray or ECT should include the assessment of contraindications, age, severity of disease, presence of psychotic symptoms, patient preference and treatment accessibility. We conclude that both treatment options are highly effective in TRD. If both are indicated, pragmatically esketamine will be chosen before ECT; however, ECT studies in ketamine non-responders are missing.

Electroconvulsive Therapy for the Treatment of Somatic Delusions.

Somatic delusions occur in various psychiatric disorders and are associated with higher mortality and lower quality of life. In this case report, we present a 68-year-old man with the diagnosis of schizoaffective disorder, bipolar type with associated somatic delusions, and auditory hallucinations. His somatic delusions were alleviated by the 20th ECT treatment with additional clinical improvements in his speech, thought processes, and judgment. This case report supports the utilization of ECT for patients with schizoaffective disorder and somatic delusions.

Genesis of Mental Disorders: Could It Be Cavum Septum Pellucidum (CSP) et Vergae? A Case Report of CSP in Schizophrenia with Catatonia.

In our case report, a 29-year-old male patient with a known history of schizophrenia presented with altered mental status and catatonia and was found to have an enlarged (21mm) cavum septum pellucidum (CSP) on magnetic resonance imaging (MRI). He was subsequently treated with escitalopram, olanzapine, methylphenidate, lorazepam, and eight electroconvulsive therapy (ECT) treatments during his hospital course, after which his catatonia improved. We compared this to other cases in which a large CSP was identified and discussed the possibility of increased susceptibility to psychosis, specifically catatonia, which might be associated with this developmental anomaly.

Molecular basis underlying changes of brain entropy and functional connectivity in major depressive disorders after electroconvulsive therapy.

INTRODUCTION: Electroconvulsive therapy (ECT) is widely used for treatment-resistant depression. However, it is unclear whether/how ECT can be targeted to affect brain regions and circuits in the brain to dynamically regulate mood and cognition. METHODS: This study used brain entropy (BEN) to measure the irregular levels of brain systems in 46 major depressive disorder (MDD) patients before and after ECT treatment. Functional connectivity (FC) was further adopted to reveal changes of functional couplings. Moreover, transcriptomic and neurotransmitter receptor data were used to reveal genetic and molecular basis of the changes of BEN and functional connectivities. RESULTS: Compared to pretreatment, the BEN in the posterior cerebellar lobe (PCL) significantly decreased and FC between the PCL and the right temporal pole (TP) significantly increased in MDD patients after treatment. Moreover, we found that these changes of BEN and FC were closely associated with genes' expression profiles involved in MAPK signaling pathway, GABAergic synapse, and dopaminergic synapse and were significantly correlated with the receptor/transporter density of 5-HT, norepinephrine, glutamate, etc. CONCLUSION: These findings suggest that loops in the cerebellum and TP are crucial for ECT regulation of mood and cognition, which provides new evidence for the antidepressant effects of ECT and the potential molecular mechanism leading to cognitive impairment.

Clinical efficacy of adjunctive esketamine anesthesia in electroconvulsive therapy for major depressive disorders: A pragmatic, randomized, controlled trial.

Electroconvulsive therapy (ECT) is an effective treatment for depression, and esketamine has been shown to have antidepressant effects. However, it is currently unclear whether adjunctive esketamine can enhance the clinical efficacy of ECT in real-world clinical practice. In this pragmatic clinical trial, patients with major depression were randomly assigned into two groups: patients received 0.25 mg/kg esketamine plus propofol (esketamine group) or the same volume of saline (control group) plus propofol. Results indicated that there was no difference in response and remission rates between the two groups. However, patients receiving esketamine had a higher remission rate of SI and lower psychotic scores. Patients receiving esketamine also required a lower electric dose, but the seizure duration and cognitive function were comparable between the two groups. Diastolic blood pressure increased after esketamine injection, but there was no increased risk of hypertension. Furthermore, incidence of delirium and confusion were comparable between the groups. Conclusively, adjunctive esketamine anesthesia does not provide any advantage in improving the response and remission rates of ECT. However, it can improve remission of SI and alleviate accompanying psychotic symptoms in depressive patients. With adjunctive usage, the adverse cardiovascular and neuropsychiatric events associated with esketamine appear to be tolerable.

The efficacy of electroconvulsive therapy in adolescent major depressive disorder with suicidal ideation: A propensity score-matched, retrospective cohort study.

BACKGROUND: More evidence is needed to validate the use of ECT in adolescent depression. This study aims to compare the effectiveness of electroconvulsive therapy (ECT) to conventional medication therapy for adolescents with major depression with suicidal ideation. METHODS: In this retrospective cohort study, we reviewed inpatient records from the First Affiliated Hospital of Chongqing Medical University spanning December 2016 to June 2021. We focused on adolescents diagnosed with severe depression presenting with suicidal tendencies. To equalize baseline differences between patients, we used the one-to-one propensity score matching to match patients who received ECT treatment with those who did not. Multivariate regression analysis was utilized to adjust for potential confounders, and subgroup analyses and sensitivity analyses were conducted to verify the robustness of our findings. RESULTS: Of the 626 patients in this study, 474 underwent ECT treatment while 152 received medication treatment, all aged between 10 and 18 years. Once matched, each group contained 143 patients. The ECT group demonstrated a significantly higher response rate and greater reductions in both Hamilton Depression Rating Scale and Hamilton Anxiety Scale scores (all P < 0.001). Additionally, the ECT group was more effective in reducing suicidal ideation, with fewer individuals retaining such ideation at discharge. In the multivariable regression analysis, both ECT treatment and shorter disease duration were independently linked to enhanced antidepressant efficacy. Subgroup analyses and sensitivity analyses verified the robustness of the main study effect. CONCLUSIONS: For adolescents with major depressive disorder and suicidal ideation, combining ECT with pharmacotherapy is more effective than pharmacotherapy alone before medications reach full effect.

Effect of Different Doses of Sugammadex on Recovery and Hemodynamic Parameters in Reversing Neuromuscular Blockade in Patients Undergoing Electroconvulsive Therapy.

Objective: This retrospective observational study aimed to investigate the effect of different doses of sugammadex used in reversing neuromuscular blockade in electroconvulsive therapy (ECT) procedures on patient recovery and hemodynamic measurements. Methods: Anesthesia induction was performed using propofol (1 mg/kg) and rocuronium (0.4 mg/kg). Patients were classified into group 2 (2 mg/kg) and group 3 (3 mg/kg) according to the dose of sugammadex used to reverse neuromuscular blockade. The patient's spontaneous breathing time, eye-opening time, time to comply with voluntary commands, time to reach Modified Aldrete score (MAS) 9, complications, and hemodynamic data were analyzed. Results: In total, 314 ECT sessions were performed on 46 patients. The average age of the patients was 38.3±12.6 years, and 56.6% (n=26) were male. While the average number of ECTs applied to the patients was 6.8±2.8, the average seizure duration was 28.2±12.7 seconds. The most common diagnosis (32.7%) in patients who underwent ECT was bipolar disorder. The average time to recovery of spontaneous breathing, eyeopening time, time to comply with voluntary commands, and time to reach MAS 9 were found to be significantly lower in group 3 (p<0.001, p<0.001, p<0.001, and p=0.002, respectively). Tooth damage was observed in 0.3% (n=1) and tongue abrasion in 0.6% (n=2) of the cases. Hemodynamic measurements were similar between groups (p>0.05). Conclusions: Sugammadex used at a dose of 3 mg/kg in ECT procedures significantly reduces recovery times compared with 2 mg/kg. However, both doses can be safely and cost-effectively used to reverse the neuromuscular blockade provided by 0.4 mg/kg rocuronium.

Exploring Brain and Heart Interactions during Electroconvulsive Therapy with Point-of-Care Ultrasound.

BACKGROUND: Electroconvulsive therapy (ECT) is a procedure commonly used to treat a number of severe psychiatric disorders, including pharmacologic refractory depression, mania, and catatonia by purposefully inducing a generalized seizure that results in significant hemodynamic changes as a result of an initial transient parasympathetic response that is followed by a marked sympathetic response from a surge in catecholamine release. While the physiologic response of ECT on classic hemodynamic parameters such as heart rate and blood pressure has been described in the literature, real-time visualization of cardiac function using point-of-care ultrasound (POCUS) during ECT has never been reported. This study utilizes POCUS to examine cardiac function in two patients with different ages and cardiovascular risk profiles undergoing ECT. METHODS: Two patients, a 74-year-old male with significant cardiovascular risks and a 23-year-old female with no significant cardiovascular risks presenting for ECT treatment, were included in this study. A portable ultrasound device was used to obtain apical four-chamber images of the heart before ECT stimulation, after seizure induction, and 2 min after seizure resolution to assess qualitative cardiac function. Two physicians with expertise in echocardiography reviewed the studies. Hemodynamic parameters, ECT settings, and seizure duration were recorded. RESULTS: Cardiac standstill was observed in both patients during ECT stimulation. The 74-year-old patient with a significant cardiovascular risk profile exhibited a transient decline in cardiac function during ECT, while the 23-year-old patient showed no substantial worsening of cardiac function. These findings suggest that age and pre-existing cardiovascular conditions may influence the cardiac response to ECT. Other potential contributing factors to the cardiac effects of ECT include the parasympathetic and sympathetic responses, medication regimen, and seizure duration with ECT. This study also demonstrates the feasibility of using portable POCUS for real-time cardiac monitoring during ECT. CONCLUSION: This study reports for the first time cardiac standstill during ECT stimulation visualized using POCUS imaging. In addition, it reports on the potential differential impact of ECT on cardiac function based on patient-specific factors such as age and cardiovascular risks that may have implications for ECT and perioperative anesthetic management and optimization.

Catatonia: A deep dive into its unfathomable depths.

This editorial addresses catatonia, a complex neuropsychiatric syndrome characterised by a spectrum of psychomotor disturbances. The editorial seeks to clarify the ambiguous aspects of catatonia, integrating recent research findings, including global studies and diagnostic advancements. It discusses catatonia's clinical manifestations, prevalence, and associated psychiatric and medical conditions, with particular emphasis on its frequent co-occurrence with schizophrenia and mood disorders. The prevalence of catatonia, which varies across psychiatric populations, is illustrated by a significant study conducted in Nelson Mandela Bay, South Africa. This study provides valuable insights into the effectiveness of the Bush-Francis Screening Instrument compared to the Diagnostic and Statistical Manual 5 criteria in diagnosing catatonia. The editorial evaluates treatment approaches, primarily focusing on benzodiazepines and electroconvulsive therapy, and discusses emerging therapeutic strategies. It underscores the importance of robust diagnostic frameworks and early intervention in managing catatonia, as recommended by the latest evidence-based consensus guideline. Furthermore, it suggests future research directions, particularly in exploring the neurobiological and genetic factors of catatonia, to enhance our understanding and improve treatment outcomes. This editorial succinctly aims to demystify catatonia and provide valuable insights for clinicians and researchers in mental health care.

An audit and analysis of electro convulsive therapy patient information sheets used in local health districts in New South Wales Australia.

Electroconvulsive Therapy (ECT) is a widely used psychiatric treatment; however, it remains contentious. It is therefore important that people are provided with accurate and balanced information before consenting to ECT. The aim of this study was to audit and analyse the content and language of ECT information sheets used in local health districts (LHDs) across the state of New South Wales Australia. Descriptive content analysis and evaluative linguistic analysis were used to investigate the information sheets, with findings then considered from a mad studies perspective. Thirteen ECT information sheets were obtained and reviewed, with the audit finding they lacked accuracy and balance. Linguistic tools were used to exaggerate positive outcomes and minimise negative effects. Despite commonalities, the structure and content of the sheets varied considerably. Findings indicate a need for co-design and co-production approaches to developing ECT information sheets. This should occur in genuine partnership with lived experience representatives based on current evidence, using neutral language, and with attention to their intent as part of processes of informed consent and decision making.

Parkinson's disease psychosis management: an evidence based, experience informed, pragmatic approach.

INTRODUCTION: Psychotic symptoms in people with Parkinson's disease (PD) have attracted increasing. Recommendations on treating psychosis often fail to take into account what psychotic symptoms require treatment, which has been complicated by the increasing number of reports documenting the frequency of 'minor' hallucinations. AREAS COVERED: This article focuses both on the phenomenology of psychotic symptoms and their management. EXPERT OPINION: Understanding the nature and implications of the types of psychotic symptoms in PD is the key to proper treatment. Evidence and experience-based data on the effect of anti-psychotic medications will be reviewed and how the various clinical settings should determine the treatment approach. The evidence base consists of all reported blinded trials recorded in PubMed and the experience-based studies are those chosen by the author from PubMed as illustrative. Specific recommendations for the treatment of psychosis will be listed for specific situations. Pimavanserin is the first-line choice for mild symptoms; quetiapine for symptoms that require improvement in a short period and clozapine for urgent problems or those which fail the other approaches.

Psychotic symptoms are common in PD, affecting the majority of patients by the time of death. 'Minor hallucinations' rarely require treatment but formed hallucinations and delusions often do. The vast majority of patients requiring treatment are on medications for PD motor problems. Some patients can be treated with reduction of psychoactive medications that are unrelated to PD, and some may tolerate reductions in PD medications without intolerable worsening of motor function. The remainder require treatment with medications that reduce psychotic symptoms, which include cholinesterase inhibitors, clozapine, pimavanserin, and possibly quetiapine and electroconvulsive therapy. Only clozapine and pimavanserin have unequivocal evidence for efficacy and motor tolerance. Data will be reviewed in support of each of these medications will be reviewed and pragmatic suggestions based on a large experience on when each might be used, and in what order they may be tried if initial approaches fail.

Restoration of postictal cortical activity after electroconvulsive therapy relates to recovery of orientation in person, place, and time.

BACKGROUND: Most patients show temporary impairments in clinical orientation after electroconvulsive therapy (ECT)-induced seizures. It is unclear how postictal reorientation relates to electroencephalography (EEG) restoration. This relationship may provide additional measures to quantify postictal recovery and shed light on neurophysiological aspects of reorientation after ECT. METHODS: We analyzed prospectively collected clinical and continuous ictal and postictal EEG data from ECT patients. Postictal EEG restoration up to 1 h was estimated by the evolution of the normalized alpha-delta ratio (ADR). Times to reorientation in the cognitive domains of person, place, and time were assessed postictally. In each cognitive domain, a linear mixed model was fitted to investigate the relationships between time to reorientation and postictal EEG restoration. RESULTS: In total, 272 pairs of ictal-postictal EEG and reorientation times of 32 patients were included. In all domains, longer time to reorientation was associated with slower postictal EEG recovery. Longer seizure duration and postictal administration of midazolam were related to longer time to reorientation in all domains. At 1-hour post-seizure, most patients were clinically reoriented, while their EEG had only partly restored. CONCLUSIONS: We show a relationship between postictal EEG restoration and clinical reorientation after ECT-induced seizures. EEG was more sensitive than reorientation time in all domains to detect postictal recovery beyond 1-hour post-seizure. Our findings indicate that clinical reorientation probably depends on gradual cortical synaptic recovery, with longer seizure duration leading to longer postsynaptic suppression after ECT seizures.