Baseline levels of miR-223-3p correlate with the effectiveness of electroconvulsive therapy in patients with major depression.

There is a strong medical need to develop suitable biomarkers to improve the diagnosis and treatment of depression, particularly in predicting response to certain therapeutic approaches such as electroconvulsive therapy (ECT). MicroRNAs are small non-coding RNAs that have the ability to influence the transcriptome as well as proteostasis at the systems level. Here, we investigate the role of circulating microRNAs in depression and response prediction towards ECT. Of the 64 patients with treatment-resistant major depression (MDD) who received ECT treatment, 62.5% showed a response, defined as a reduction of ≥50% in the MADRS total score from baseline. We performed smallRNA sequencing in blood samples that were taken before the first ECT, after the first and the last ECT. The microRNAome was compared between responders and non-responders. Co-expression network analysis identified three significant microRNA modules with reverse correlation between ECT- responders and non-responders, that were amongst other biological processes linked to inflammation. A candidate microRNA, namely miR-223-3p was down-regulated in ECT responders when compared to non-responders at baseline. In line with data suggesting a role of miR-223-3p in inflammatory processes we observed higher expression levels of proinflammatory factors Il-6, Il-1b, Nlrp3 and Tnf-α in ECT responders at baseline when compared to non-responders. ROC analysis of confirmed the diagnostic power of miR-223-3p demarcating ECT-responders from non-responder subjects (AUC = 0.76, p = 0.0031). Our data suggest that miR-223-3p expression and related cytokine levels could serve as predictors of response to ECT in individuals with treatment-resistant depressive disorders.

The myth of brain damage: no change of neurofilament light chain during transient cognitive side-effects of ECT.

Electroconvulsive therapy (ECT) is an effective, safe, and mostly well-tolerated treatment for patients with severe or difficult to treat depression or psychotic disorders. However, a relevant number of patients experience subjective and/or objective cognitive side-effects. The mechanism of these transient deficits is not yet clear. Thus, our study prospectively investigated neurofilament light chain (NfL) concentrations as a highly sensitive biomarker for neuroaxonal damage along with cognitive performance during a course of ECT. Serum NfL concentrations from 15 patients with major depressive disorder receiving ECT were analyzed (1) 24 h before the first ECT, (2) 24 h and (3) 7 days after the last ECT (45 measurements in total). Neuropsychological testing including memory, executive functions and attention was performed at each time-point. NfL concentrations did not change between the three time-points, while a temporary cognitive impairment was found. Even in the subset of patients with the strongest impairment, NfL concentrations remained unchanged. Neuropsychological testing revealed the common pattern of transient cognitive side-effects with reduced performance 24 h post-ECT (global cognition score: p < 0.001; memory: p = 0.043; executive functions: p = 0.002) and return to baseline after 7 days (all p < 0.001). Our study adds to the evidence that neither ECT per se nor the transient cognitive side-effects seem to be associated with an increase of NfL as a marker of neuroaxonal damage. In contrast, we discuss cognitive side effects to be potentially interpreted as a byproduct of ECT's neuroplastic effects.

[Electroconvulsive Therapy in the New National Guideline Depression: Effectiveness, Evidence, and Grade of Recommendation]. / Elektrokonvulsionstherapie in der neuen NVL Depression: vom Unterschied zwischen Effektivität, Evidenz und Empfehlungsgraden.

In comparison to the previous version, the new national guideline 'Unipolar Depression' comprises more differentiated statements and recommendations regarding the use of electroconvulsive therapy (ECT). In principle, this is most welcome, as it clarifies the particular significance of ECT in different clinical situations. In parallel, this differentiation of recommendations depending on the presence of specific features of depressive disorders (e. g., psychotic symptoms, suicidality) led to different grades of recommendations for ECT. This may be correct and rational under the strict methodology of a guideline process, but nevertheless may appear confusing and contradictory in clinical practice. This article describes the relationships and putative discrepancies between the effectiveness of ECT, scientific evidence, and grading of guideline recommendations with comments on these for clinical practice from experts' point of view.

Effects of Anesthesia Changes During Maintenance ECT: A Longitudinal Comparison of Seizure Quality Under Anesthesia Using Propofol/Esketamine Versus Methohexital.

INTRODUCTION: The effectiveness of ECT relies on the induction of a generalized cerebral seizure. Among others, seizure quality (SQ) is potentially influenced by the anesthetic drug used. Commonly used anesthetics comprise barbiturates, etomidate, propofol, and esketamine, with different characteristics and impacts on seizure parameters. So far, no studies have compared the influence of methohexital vs. a combination of propofol/esketamine on established SQ parameters. METHODS: This retrospective longitudinal study compared eight established SQ parameters (PSI, ASEI, MSC, midictal amplitude, motor and electroencephalography (EEG) seizure duration, concordance, PHR) before and after the change from propofol/esketamine to methohexital in 34 patients under maintenance ECT. Each patient contributed four measurements, two before and two after the anesthesia change. Anesthesia dose, stimulus dose, electrode placement, and concomitant medication remained unchanged throughout the analyzed treatments. RESULTS: Under methohexital (M=88.97 mg), ASEI (p=0.039 to 0.013) and midictal amplitude (p=0.022 to<0.001) were significantly lower, whereas seizure duration (motor and EEG) was significantly longer when compared to propofol/esketamine (M=64.26 mg/51.18 mg; p=0.012 to<0.001). PSI, MSC, seizure concordance, and PHR were not affected by the anesthetic used. DISCUSSION: Although to what extent these parameters correlate with the therapeutic effectiveness remains ambiguous, a decision for or against a particular anesthetic could be considered if a specific SQ parameter needs optimization. However, no general superiority for one specific substance or combination was found in this study. In the next step, anesthetic effects on treatment response and tolerability should be focused on.

[Health service aspects of electroconvulsive therapy: analysis of external referrals to a university medical center]. / Versorgungsaspekte der Elektrokonvulsionstherapie: Analyse der externen Zuweisungen an ein universitäres Zentrum.

BACKGROUND: The application of ECT in Germany varies widely depending on regional availability. This shortfall in ECT supply is partly compensated via referrals to hospitals with ECT services, yet restricted by limited resources in these clinics. OBJECTIVE: External referrals for ECT were investigated at the University Medical Center Göttingen. We analyzed the referring institutions, patient characteristics, pharmacotherapy according to current guidelines before indications for ECT, and clinical outcome in cases of treatment with ECT. MATERIAL AND METHODS: All external referrals were systematically recorded and retrospectively evaluated for the time span of 1 year. Besides descriptive presentation of the data, pharmacological pretreatment was compared with the current guideline recommendations. We used overall clinical impression (CGI-I) to determine the treatment response post-ECT. RESULTS: External referrals were made for N = 52 patients, 82.7% of whom were from the inpatient setting and from a distance of up to 300 km. The most common diagnoses were unipolar depression (57.7%), followed by schizophrenia spectrum (36.5%). Prior to referral, at least one guideline-based pretreatment was given in the majority of cases. ECT was performed in 18 patients in our hospital, of whom 72.7% showed a good to very good response. CONCLUSION: Both numbers and radius of external referrals indicate a high unmet need for ECT and thus limited access to this evidence-based and guideline-recommended therapy. As treatment close to home should be the goal, more hospitals are needed to establish (or expand) ECT services; however, even with considerable delays which are often associated with external referrals, the response rate is good across all diagnoses.

Effectiveness of electroconvulsive therapy in patients lacking decision making capacity: A systematic review and meta-analysis.

BACKGROUND: Electroconvulsive therapy (ECT) is provided for patients with severe and often life-threatening illness, who lack decision making capacity to consent to treatment (DMC-T) in clinical settings. OBJECTIVE: The aim of this study is to summarize previous studies investigating clinical outcomes of ECT in patients lacking DMC-T. METHODS: A systematic review and meta-analysis of studies reporting clinical outcomes of ECT in patients lacking DMC-T with any psychiatric diagnoses was conducted. The primary outcome was clinical improvement. Secondary outcomes were cognitive outcomes and six month readmission rate. Hedges' g and odds ratios were calculated using a random-effects model. The protocol was registered in Open Science Framework (https://osf.io/rxjkm). RESULTS: Of 3552 identified articles, 41 studies (n = 1299) were included. Approximately 80% of patients lacking DMC-T responded to ECT, and part of the patients regained capacity to consent and consented to further treatment with ECT. A total of seven studies (n = 1081) were included for meta-analysis. Patients without DMC-T showed superior clinical improvement and less cognitive side effects compared with those with DMC-T, whereas the groups did not show any difference in readmission rate. Several clinical characteristics at baseline and ECT techniques were significantly different between the groups. CONCLUSION: ECT is equally, if not superiorly, effective in patients lacking DMC-T compared to patients with DMC-T. ECT can potentially enhance patients' autonomy, without increasing the risk of cognitive side effects. These results support the clinical and ethical legitimacy of ECT provision for patients with the most severe illness who lack DMC-T at start of treatment.

Electroconvulsive Therapy in Children and Adolescents in Germany-A Case Series From 3 University Hospitals.

OBJECTIVE: Electroconvulsive therapy (ECT) is a well-established, safe, and efficacious treatment for severe psychiatric disorders. In children and adolescents, it is used much less frequently than in adults, likely because of a lack of knowledge. METHODS: We retrospectively analyzed all patients aged 12 to 17 years who completed a course of ECT at 3 psychiatric university hospitals in Germany between 2010 and 2020. Clinical Global Impression Severity (CGI-S) scores were assessed based on electronic medical records. Changes in CGI-S scores were assessed using a paired samples t test. Predictors for response and remission were assessed using binomial logistic regression. RESULTS: We included 32 patients. The CGI-S scores improved significantly from before to after ECT treatment (6.9 vs 3.9, t = 10.0, P < 0.01). A total of 40.6% of patients responded (CGI ≤ 3) and 21.9% remitted (CGI ≤ 2). The number of ineffective medication trials in the 6 months before ECT treatment was significantly associated with response (odds ratio, 0.54; P = 0.028) and remission (odds ratio, 0.31; P = 0.048). Five patients reported subjective cognitive adverse effects, 2 patients exhibited a prolonged seizure, 1 patient reported headaches, and 1 patient experienced a mild allergic reaction after anesthesia with etomidate. A total of 65.6% of patients experienced no adverse effects at all. CONCLUSIONS: This retrospective analysis found ECT to be effective and safe in children and adolescents irrespective of their main diagnosis. The reported data point to the importance of an early use of ECT for severe psychiatric diseases in child and adolescent psychiatry.

[The Strandet Ill: Long-Term-Inpatients in Psychiatric Hospitals and Departments]. / Die gestrandeten Kranken: Langzeitpatientinnen und -patienten in psychiatrischen Fachkrankenhäusern und Abteilungen.

In contrast to official mental health policy, psychiatric clinics accomodate long-term patients. AIM: To quantify this problem. METHOD: Cross-sectional assessment of the number of long-term patients in psychiatric clinics in Lower Saxony. RESULTS: 13 clinics of adult psychiatry report 60 long-term patients and one clinic for child and adolescent psychiatry reports 2 patients. Median duration of stay 9.5, maximum 215 months. Reasons for long-term hospitalisation include patients' challenging behaviour and, consequently, difficulties to find an accommodating long-term facility. DISCUSSION AND CONCLUSION: Housing willing to accommodate mentally ill persons with challenging behaviour is lacking, as well as local responsibility for the placement of these persons. Systematic transfer management from hospital to residential homes does not exist.

Evidence and expert consensus based German guidelines for the use of repetitive transcranial magnetic stimulation in depression.

INTRODUCTION: Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) offer a promising alternative to psychotherapeutic and pharmacological treatments for depression. This paper aims to present a practical guide for its clinical implementation based on evidence from the literature as well as on the experience of a group of leading German experts in the field. METHODS: The current evidence base for the use of rTMS in depression was examined via review of the literature. From the evidence and from clinical experience, recommendations for the use of rTMS in clinical practice were derived. All members of the of the German Society for Brain Stimulation in Psychiatry and all members of the sections Clinical Brain Stimulation and Experimental Brain Stimulation of the German Society for Psychiatry, Psychotherapy, Psychosomatics and Mental Health were invited to participate in a poll on whether they consent with the recommendations. FINDINGS: Among rTMS experts, a high consensus rate could be identified for clinical practice concerning the setting and the technical parameters of rTMS treatment in depression, indications and contra-indications, the relation of rTMS to other antidepressive treatment modalities and the frequency and management of side effects.

Effectiveness of maintenance electroconvulsive therapy-Evidence from modifications due to the COVID-19 pandemic.

OBJECTIVE: Continuation and maintenance ECT (c-/m-ECT) are effective in the prevention of relapse and recurrence of both affective and psychotic disorders. However, data are scarce concerning the trajectories of severe mental disorders after the end of c-/m-ECT. This prospective study investigates the clinical outcome of patients with versus without modifications of their c-/m-ECT schedules. METHODS: In the context of the COVID-19 pandemic, ECT capacities were restricted at many clinics in early 2020. All patients receiving c-/m-ECT in March and April 2020 at our department (n = 53, unipolar depression, bipolar disorder, schizophrenia) were followed up for six months to investigate the impact of treatment modifications imposed by the pandemic. Based on individual decisions, c-/m-ECT was either (a) continued without modification, (b) continued with reduced frequency, or (c) discontinued. RESULTS: Both reduced frequency and discontinuation of c-/m-ECT were associated with significant clinical deterioration as measured by CGI-I (Clinical Global Impression Scale - Global Improvement) during the six-month follow-up when compared to the subgroup of patients without any treatment modification (p = 0.005, p = 0.011). Furthermore, patients with discontinued or reduced c-/m-ECT showed significantly higher rates of rehospitalizations (p = 0.028) and new acute courses of ECT (p = 0.018). CONCLUSION: Despite the limitations of a heterogeneous and relatively small sample, our study strongly corroborates the effectiveness of c-/m-ECT in a real-world population. Especially, patients with shorter time since index ECT seem to be at high risk for severe clinical deterioration in the case of treatment discontinuation or reduction.

[Use of electroconvulsive therapy in adolescents - A retrospective survey on 12- to 17-year-old patients at three university hospitals in Germany]. / Elektrokonvulsionstherapie im Kindes- und Jugendalter.

Use of electroconvulsive therapy in adolescents - A retrospective survey on 12- to 17-year-old patients at three university hospitals in Germany Abstract. Abstract. Background: Electroconvulsive therapy (ECT) is a highly effective and well-researched therapy in adult psychiatry and has been successfully used especially as a treatment for severe depressive, catatonic, and psychotic disorders. Although severe disease progressions also occur in child and adolescent psychiatry, ECT is used much less frequently there. This may be because hardly any data have been collected on the use, effectiveness, and tolerability of ECT in child and adolescent psychiatric patients. This article outlines the application, effectiveness, and tolerability of ECT when applied to young adolescents in Germany. Methods: A retrospective survey on ECT in 29 patients under 18 years of age was conducted at three German university centers. All documented cases were recorded and evaluated for effectiveness and tolerability. In addition, a comprehensive PubMed-based database search was carried out. Results and conclusions: Internationally, there are no meta-analyses or randomized controlled studies and hardly any published cases on electroconvulsive therapy in German child and adolescent psychiatry. Our data on ECT show high efficacy in previously treatment-resistant and severely ill patients. Side effects occurred rarely. There was no evidence of differences between adults and adolescents in indication (depression, catatonia, schizophrenia), effectiveness, tolerability, and negative predictors of response to ECT. The results also suggest that the use of ECT in adolescents should be considered earlier in the treatment course.

[Electroconvulsive therapy in pregnancy: case report and interdisciplinary treatment suggestions]. / Elektrokonvulsionstherapie in der Schwangerschaft: Fallbericht und interdisziplinäre Behandlungsvorschläge.

BACKGROUND: Psychiatric disorders during pregnancy are common. Electroconvulsive therapy (ECT) can be indicated in severely affective or psychotic disorders with the necessity of a rapid response. Currently available review articles greatly differ in the methodology, leading to divergent conclusions concerning the use of ECT during pregnancy. OBJECTIVE: Description of a new clinical case and interdisciplinary treatment suggestions for the safe application of ECT in pregnancy. METHODS: Clinical case report and selective review of the literature with special consideration of existing systematic reviews. RESULTS AND CONCLUSION: This case report shows the potentially high effectiveness and safe administration of ECT in pregnancy for both mother and fetus. The undesired adverse events associated with ECT described in the literature are largely qualitatively congruent with the risks of severe psychotic disorders in pregnancy per se. For a better risk-benefit analysis, larger case control studies would be desirable. Under the premise of a thorough evaluation of the indications, good interdisciplinary coordination and consideration of the specific practical requirements, ECT is a useful therapeutic option in pregnancy.

[Importance of electroconvulsive therapy (ECT) in forensic psychiatry]. / Stellenwert der Elektrokonvulsionstherapie (EKT) in der forensischen Psychiatrie.

BACKGROUND AND OBJECTIVE: Electroconvulsive therapy (ECT) is recommended in guidelines for the treatment of severe affective and psychotic disorders that also can be found in patients in forensic psychiatric commitment; however, there are no systematically collected data concerning the use of ECT in forensic psychiatry. The aim of this study was to investigate the current state and estimated need for ECT in forensic psychiatry in Germany. MATERIAL AND METHODS: A questionnaire was designed consisting of questions about the current practice and estimated need for ECT in this population. This questionnaire was sent electronically (and by post if needed) to the forensic psychiatric hospitals in Germany. RESULTS: We received replies from 52 hospitals (66%) and 29 of these hospitals stated that they were capable of treating patients with ECT. An indication for ECT treatment was seen in 3.4% of all detained patients across all forensic hospitals. In 1 year (2018) 32 ECT treatment courses were carried out with on average good effectiveness and a mean clinical global impressions (CGI) scale of 2.32. The most frequent reason for not using ECT was lack of structural requirements. Approximately one third of the forensic psychiatric hospitals stated that there was a medium or even high need for ECT in forensic psychiatry. CONCLUSION: The use of ECT in German forensic psychiatry is currently very limited. It is striking that the number of applied ECT treatments is eight times lower in comparison to the frequency of indications. Nevertheless, approximately two thirds of the forensic hospitals stated a medium or high need for ECT, which seems to suggest a shortage of ECT in the treatment of forensic psychiatry patients.