Schizophrenia is one of the most severe and costly mental disorders in terms of human suffering and societal expenditure. About 15-30% of patients do not respond to all known antipsychotics, including clozapine, the current gold standard in these cases. Electroconvulsive therapy (ECT) is well-known to be highly effective in clozapine-treatment-resistant schizophrenia (CRS), and synergistic effects of clozapine and ECT have been demonstrated. However, relapse rates after successful courses of ECT are still very high, and evidence for maintenance ECT (mECT) in CRS is scarce at best.

Here, we present the protocol of the MECT-RESIST trial, a German multi-center, observer-blind, randomized, and actively controlled parallel-group clinical trial. The scientific aim of the study is to test the hypothesis that mECT plus treatment as usual (TAU) (intervention group) is superior to TAU alone (control group) for relapse prevention in CRS. The primary endpoint is time to relapse. Secondary endpoints include the proportion of relapse-free patients, the global level of functioning and quality of life, depressive symptoms, overall symptoms of schizophrenia, concomitant catatonic symptoms, stress and self-stigmatization and cognitive performance. We aim at randomizing 84 patients between 18 and 65 years with a clinically diagnosed CRS and brief psychotic rating scale (BPRS) > 45, who responded to a series of ECT (BPRS < 70% of initial BPRS), to either recieve mECT + TAU or TAU over a period of 28 weeks followed by a follow-up of 12 months. The study will be performed between 2025 and 2028.

In this multi-center trial, we aim to examine the effectiveness of mECT in CRS patients who improved after a course of routine ECT. If mECT will lead to a longer time to relapse and/or to a higher proportion of relapse-free patients compared to those undergoing treatment as usual, this trial would have an enormous impact on therapeutic strategies for patients with CRS and would induce a profound change of current treatment guidelines, where ECT still ranks at the level of ultima ratio, despite accumulating evidence suggesting otherwise.

ClincalTrials.gov NCT06456983, registered 7 Jun 2024. Deutsches Register Klinischer Studien DRKS00036886, registered 14 May 2025.

In this review, we explore the biomarkers of different psychiatric disorders, such as major depressive disorder, generalized anxiety disorder, schizophrenia, and bipolar disorder. Moreover, we show the interplay between genetic and environmental factors. Novel techniques such as genome-wide association studies (GWASs) have identified numerous risk loci and single-nucleotide polymorphisms (SNPs) implicated in these conditions, contributing to a better understanding of their mechanisms. Moreover, the impact of genetic variations on drug metabolisms, particularly through cytochrome P450 (CYP450) enzymes, highlights the importance of pharmacogenomics in optimizing psychiatric treatment. This review also explores the role of neurotransmitter regulation, immune system interactions, and metabolic pathways in psychiatric disorders. As the technology advances, integrating genetic markers into clinical practice will be crucial in advancing precision psychiatry, improving diagnostic accuracy and therapeutic interventions for individual patients.

Clozapine is used in the management of treatment-resistant schizophrenia. Although the reported adverse effects with clozapine are more, and the risk of clozapine discontinuation is present, few Indian studies have examined the correlates of clozapine discontinuation. Furthermore, there is a lack of consensus on alternative treatment after clozapine discontinuation. This study aimed to explore these factors among patients treated in a tertiary psychiatric centre in India.

We performed a retrospective chart review of the clozapine database from tertiary care schizophrenia clinic services (2015-2023) and identified 30 eligible case records of clozapine discontinuation. We examined the correlates of clozapine discontinuation.

Among patients who discontinued clozapine, 66.7 % were male, with an average age of 32.30 ± 9.78 years. The most common causes for discontinuation were adverse effects(56.67 %), inadequate therapeutic response(23.34 %), and non-adherence(13.33 %). Down-titration was used for 58.82 % (10/17 in whom discontinuation method details were available) of patients, with no withdrawal adverse effects noted. Clozapine retrial was considered among nine patients. Following clozapine discontinuation, among the interventions tried, ECT showed a significant response, followed by haloperidol and risperidone. Amisulpride, olanzapine, and flupentixol depot showed a moderate response.

These results align with previous studies, showing that adverse effects and inadequate response are prominent reasons for clozapine discontinuation and demonstrate the possibility of clozapine retrial in selected patients. Managing adverse effects might result in improvement, at least to a mild degree. Clozapine discontinuation can be avoided in a cohort with non-serious adverse effects, given the superiority of clozapine in resistant schizophrenia.

The field of neuromodulation has evolved tremendously and now includes a vast array of interventions utilizing different technologies that span electrical, magnetic, and ultrasound forms of stimulation. The evolution of interventions holds the promise of fewer adverse effects and a noninvasive approach, increasing the scale at which these interventions may be offered in hospital and community settings. While the majority of neuromodulation studies have focused on patients with mood disorders, predominantly depression, there is an unmet need for patients with schizophrenia, who are in dire need of novel therapeutic options. Advances in neuroimaging and approaches for examining individual variability and transdiagnostic symptoms may lead to more effective neuromodulation treatments in this patient population. This overview explores the modern landscape of invasive and noninvasive neuromodulation treatments for patients with schizophrenia. It begins with approaches that involve diffuse stimulation of the cortex and subcortex and then reviews more focal stimulation approaches at the cortical and subcortical levels. The authors also reflect on the relationship between our understanding of the neurobiology of schizophrenia and neuromodulation interventions.

Objective: Electroconvulsive therapy (ECT) is among the most effective treatments for mood disorders and other psychotic disorders. This study meta-analyzed the effects of ECT on all-cause mortality and suicide deaths using longitudinal studies. Methods: PubMed/MEDLINE, PsycINFO, Cochrane Library, Embase, and Google Scholar were searched from inception through January 21, 2025, with no language limits. Inclusion criteria were as follow: (1) patients with diagnoses of mental disorders; (2) intervention consisted of ECT compared with placebo, usual care or another intervention; (3) all-cause mortality and suicide deaths as outcome measures; and (4) clinical trial or longitudinal cohort study designs where the aforementioned interventions preceded the observations of outcome measures. Adjusted hazard ratio [HR] with their corresponding 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. Moderator analyses were also performed. Results: Overall, 17 studies consisting of 1,182,501 individuals (n=40,867 for ECT, n=1,141,634 for those receiving comparable interventions) were included. ECT was associated with a reduction in risk of all-cause mortality (HR, 0.70 [95% CI, 0.61-0.81]; p <0.001), a finding that was consistent at 3 months, 6 months, and 12 months of follow-up. Sex demonstrated a very small moderating effect on this relationship, with ECT being slightly less protective against mortality risk for females compared to males (standardized beta coefficient, -0.01 [-0.01 to 0.00]; p =0.036). Regions also had a moderating effect ( p =0.002). Japan had the largest effect size (HR, 0.17 [0.04-0.72]) and Denmark had the smallest (HR, 0.87 [0.83-0.92]). ECT was associated with a reduction in suicide risk at 3 months of follow-up (HR, 0.53 [0.39-0.72]; p <0.001) but not at 1, 6, or 12 months of follow-up. Conclusions: ECT is associated with a reduced risk of all-cause mortality. ECT, however, was not consistently associated with a reduced risk of suicide.

Electroconvulsive therapy (ECT) is widely used to treat various psychiatric disorders, with patients often undergoing multiple courses of ECT. However, it remains unclear whether responses to one ECT course can be replicated in subsequent treatment courses. A retrospective cohort study at the Institute of Mental Health, Singapore, studied 226 patients who underwent at least two courses of ECT between March 2017 and May 2023. The study compared the correlation of response rates, illness severity, quality of life (QoL), and cognition between 2 courses of ECT using Pearson's chi-square test and Pearson correlation coefficients. The results showed no significant correlation in response rates or cognition between the two courses of ECT. However, small correlations were observed at the group level between the Clinical Global Impression - Improvement (CGI-I) scale, which measures illness severity, and the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) scores. Pearson correlation coefficients were r = 0.16 (p = 0.04) for CGI-I and r = 0.28 (p = 0.009) for Q-LES-Q-SF. In subgroup analysis, patients with schizophrenia showed a small correlation between CGI-I (r = 0.21, p = 0.029) and Q-LES-Q SF scores (r = 0.26, p = 0.048), while those with depression showed a moderate correlation in Q-LES-Q SF scores (r = 0.52, p = 0.013), with no correlation in CGI-I. No correlation was observed in the mania or catatonia subgroups. These results suggest that while previous responses to ECT may not reliably predict future outcomes, improvements in illness severity and QoL tend to follow a similar trajectory, highlighting the value of collaborative decision-making in treatment planning.

The present study is the first large-scale, multicenter survey on modified electroconvulsive therapy (ECT) in Japan. We aimed to comprehend the current implementation status of ECT based on the annual reports of 2016 from 21 facilities that were certified by the Japanese Society of General Hospital Psychiatry as ECT certified facilities and participated in this multicenter observational study.

We investigated the distributions of diagnosis, gender, and age of patients receiving acute-phase ECT, and the efficacy, safety, and adverse events.

The number of patients receiving acute-phase ECT was 524. According to International Classification of Diseases, 10th Revision, 344 patients (65.6%) were diagnosed with mood disorders (F3), 156 patients (29.8%) were diagnosed with schizophrenia and with schizotypal and delusional disorders (F2), and 151 subjects were male and 334 subjects were female. The mean age of patients was 60.4 years (SD 15.9), and patients 60 years or older accounted for 57.9%. Efficacy did not significantly differ between diagnoses, nor between genders. However, the efficacy rate was significantly higher in elderly patients. In acute-phase ECT, 4 severe adverse events occurred.

Our multicenter study confirmed that F3 (mood disorders) was the most common indication for ECT at 66%, followed by F2 (schizophrenia, schizotypal, and delusional disorders) at 30%, with no difference in efficacy, indicating that ECT is still performed as 1 of the treatment options for schizophrenia in Japan. The present results suggested that accumulation of annual data from multiple centers can be useful for more effective and safer ECT practices.

Patients with schizophrenia are the largest population in forensic hospitals, and treatment-resistant psychosis is associated with length of stay. For patients with severe and treatment-resistant psychotic disorders, electroconvulsive therapy (ECT) is a potentially effective treatment. Data regarding the use of ECT in forensic psychiatry are scarce. This systematic review aims to provide an overview of the use of ECT in forensic psychiatry. Three databases (PubMed, Web of Science, and PsycINFO) were searched for publications since 1980. Peer-reviewed articles describing patients who underwent ECT treatment in the context of forensic psychiatry were included when a treatment outcome was reported. We identified 5 case reports and 1 case series comprising 13 patients treated with ECT in forensic settings. The quality of evidence was poor accompanied by a considerable risk of bias. Patients were diagnosed with schizophrenia spectrum disorders (n = 10) or depression with psychotic features (n = 3). Eleven patients (84.6%) were described as responders in terms of symptom improvement associated with a reduction of aggressive behavior and improved functioning. At least 3 patients were able to return to community settings. Despite the very limited evidence base, our review suggests that patients in forensic hospitals may benefit from ECT, but more systematic and higher-quality evidence is urgently needed. In addition to prospective, controlled observational studies, a qualitative view focusing on patients' perspectives in this specific setting is of particular importance.

Electroconvulsive therapy (ECT) is an evidence-based treatment for schizophrenia when anti-psychotic medications do not sufficiently control symptoms of psychosis or rapid response is required. Little is known about how it is used in routine clinical practice. The aim of this study was to identify the association of demographic and clinical characteristics with administration of ECT for schizophrenia spectrum disorders (SSD).

Among psychiatric inpatients with a diagnosis of SSD in Ontario, Canada (2006-2023), patient-level socio-demographic and clinical characteristics were described in those who did and did not receive ECT. We used multi-variable logistic regression to assess the association between patient-level characteristics and administration of ECT during index hospitalization.

From 164,632 admissions, 2,168 (1.3%) involved exposure to ≥1 inpatient ECT procedure. Compared to those not receiving ECT, those receiving ECT were older, had higher rates of pre-admission medication use, medical and psychiatric comorbidities, outpatient mental health service use, but lower rates of substance use disorders. In the multi-variable logistic regression model, patient-level characteristics most strongly associated with receiving inpatient ECT were the presence of catatonia (odds ratio [OR]: 5.83; 95% confidence interval [95% CI]: 4.01-8.46), comorbid depression (OR: 2.49; 95% CI: 2.07-2.98), obsessive-compulsive disorder (OR: 2.16; 95% CI: 1.55-3.00), while characteristics most strongly associated with not receiving inpatient ECT were myocardial infarction (OR: 0.44; 95% CI: 0.20-0.95) and family conflict towards patient (OR: 0.47; 95% CI: 0.31-0.71). Neither severity of psychotic symptoms, non-command auditory hallucinations nor delusions were associated with administration of ECT.

While characteristics associated with the use of ECT are generally consistent with the indications for ECT (e.g., catatonia, mood disorders), ECT is rarely used amongst individuals with SSD. Severity of psychotic symptoms was not associated with the use of inpatient ECT suggesting an opportunity to increase the use of ECT in this population.

Patient characteristics associated with receiving electroconvulsive therapy in schizophrenia and other psychotic illnesses.

Electroconvulsive therapy (ECT) remains a target of prejudice, and finding places to administer it remains a challenge. The main reason for the recommendation of ECT is its effectiveness, especially when compared with other treatments for severe and refractory patients.

This study aimed to assess the response rates across a broader patient sample undergoing ECT in three distinct Brazilian states.

This observational cohort study was conducted at the following three sites: Universidade Federal do Tocantins (by partnership with Hospital Geral de Palmas, Palmas-TO), Pax Instituto de Psiquiatria (Goiânia - GO), and Clínica Animus (Joao Pessoa - PB).

A total of 212 patients who received ECT at three different Brazilian services were assessed for improvement in symptoms in the first week after treatment and 30 and 60 days after treatment completion.

Safety and efficacy of ECT was well established, as evidenced by the zero mortality rate among the study participants, with side effects observed in only 10.5% of cases. The immediate response rate was impressive at 95.8%, and the response rate after 30 and 60 days was 90.6% and 87.7%, respectively. The regression analysis highlighted session frequency as a key determinant of positive responses.

The effectiveness of short term ECT (two months) is one of the greatest among psychiatric treatments. Future research should focus on predictive models for treatment responses to enable personalized approaches.

To explore the short-term and long-term effects of electroconvulsive therapy (ECT) on depression among adolescents and to determine the relationship between the effects of ECT and family functioning. Sixty-five adolescent inpatients with major depressive disorder (MDD) who received ECT were recruited. We assessed the severity of MDD with the Hamilton Depression Rating Scale-24 (HDRS-24) before (T0), 1-2 days after the end of ECT treatment (T1), and 3 months after the end of ECT treatment (T2). We calculated the reduction in HDRS scores at T1 (short-term effect) and T2 (long-term effect). Additionally, we examined the relationship between family functioning and the effects of ECT. The short-term response rate to ECT was 64.6%, but the long-term response rate decreased to 22.2%. HDRS scores were significantly lower at T1 and T2 than at T0 (P < .01). Independent sample t tests showed that the mean scores for the communication, roles, affective responsiveness, affective involvement, and overall functionality dimensions of the Family Assessment Device were significantly lower in the responder group than in the nonresponder group at T2 (P < .05). Forward entry binary logistic regression showed that the short-term effects of ECT were stronger among patients who were hospitalized in a psychiatric ward for the first time, and the affective involvement dimension of the Family Assessment Device was significantly negatively correlated with the long-term effects of ECT (P < .05). ECT may be an effective intervention for MDD among adolescents; however, its short-term effects are more prominent than its long-term effects. In addition, family functioning may be related to long-term responses to ECT.

Evaluation of the effects of electroconvulsive therapy (ECT) on systemic inflammatory markers in patients with severe mental disorders and determination of potential clinical predictors of treatment response.

The current retrospective cohort study included 156 patients with psychotic and mood disorders who underwent ECT. Pre- and post-ECT blood samples were collected to assess inflammatory markers, including C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), and other complete blood count derived indices. Clinical outcomes were measured using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Severity (CGI-S).

Significant reductions in several inflammatory markers were identified, including NLR, monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), CRP and CRP-albumin ratio, following ECT. Both BPRS and CGI-S scores also showed marked improvement post-ECT. Psychotic presentation was identified as a predictor of greater symptom improvement; changes in inflammatory markers were not significantly correlated with clinical outcomes.

ECT can reduce systemic inflammation in patients with severe mental disorders; however, this reduction may not directly correspond to clinical improvement. These findings suggest that inflammation plays a complex role in the therapeutic effects of ECT.

Currently, guidance on the most effective treatment for patients with clozapine-resistant schizophrenia-spectrum disorders (SSD) is lacking. While augmentation strategies to clozapine with aripiprazole and electroconvulsive therapy (ECT) have been demonstrated to be effective in patients with clozapine-resistant schizophrenia spectrum disorders (CRS), head-to-head comparisons between these addition strategies are unavailable. We therefore aim to examine the feasibility of a larger randomized, single-blind trial comparing the effectiveness, cost-effectiveness, and safety of aripiprazole addition vs. ECT addition in CRS.

In this multi-center, randomized, single-blind feasibility study, the feasibility of recruiting 20 participants with CRS who will be randomized to either aripiprazole or bilateral ECT addition will be assessed. The main endpoint is the number of patients willing to be randomized. The number of screened individuals and reasons to decline participation will be recorded. Effects will be estimated for the benefit of the foreseen larger trial. To that end, differences between both arms in symptom severity will be assessed using blinded video assessments. In addition, tolerability (e. g., cognitive functioning), safety, quality of life, recovery, and all-cause discontinuation will be compared. The follow-up period is 16 weeks, after which non-responders will be given the option to switch to the other treatment.

Strengths of this feasibility trial include maintaining blinding with video assessment, a possibility to switch groups in case of non-response, and a broad set of outcome measures. Identification of factors contributing to non-participation and drop-out will generate valuable information on trial feasibility and may enhance recruitment strategies in a follow-up RCT.

The study has been approved by the Medical Research Ethics Committee of the Amsterdam University Medical Center, location AMC, and was registered on 1 May 2022 in the EU Clinical Trials Register (EudraCT) under the trial name 'EMECLO' (2021-006333-19).

Large-scale evidence for the efficacy of continuation and maintenance electroconvulsive therapy (c/mECT) is lacking.

To provide an exhaustive and naturalistic insight into the real-world outcomes and the cost-effectiveness of c/mECT in a large dataset.

This cohort study included all patients in the Danish National Patient Registry who initiated treatment with ECT from 2003 through 2022. The data were analyzed from October 2023 to February 2024.

ECT. An algorithm to identify c/mECTs in the dataset was developed: (>3 treatments with ≥7 and <90 days between adjacent treatments, occurring within a time frame of 180 days [cECT] or more [mECT] after an acute [aECT] series).

The association of c/mECT with subsequent 6- to 12-month risk of hospitalization or suicidal behavior using Cox proportional hazard regression with multiple adjustments and aECT only as a reference, propensity score matching, and self-controlled case series analysis using a Poisson regression model. A cost-effectiveness analysis based on hospitalization and ECT expenses was made.

A total of 19 944 individuals were treated with ECT (12 157 women [61%], 7787 men [39%]; median [IQR] age, 55 [41-70] years). Of these, 1533 individuals (7.7%) received c/mECT at any time point (1017 [5.1%] cECT only and 516 [2.6%] mECT). Compared with patients receiving aECT only, c/mECT patients more frequently experienced schizophrenia (odds ratio [OR], 2.14; 95% CI, 1.86-2.46) and schizoaffective disorder (OR, 2.42; 95% CI, 1.90-3.09) and less frequently unipolar depression (OR, 0.56; 95% CI, 0.51-0.62). In all models, c/mECT was associated with a lower rate of hospitalization after finishing aECT (eg, 6-month adjusted hazard ratio, 0.68; 95% CI, 0.60-0.78 [Cox regression]; 6-month incidence rate ratio, 0.51; 95% CI, 0.41-0.62 [Poisson regression]). There was no significant difference in the risk of suicidal behavior. Compared with the periods before the end of aECT, c/mECT was associated with a substantial reduction in total treatment costs.

In a nationwide and naturalistic setting, c/mECT after aECT was infrequently used but associated with a lower risk of readmission than aECT alone. The totality of the evidence indicates that c/mECT should be considered more often to prevent relapse after successful aECT in patients whose condition does not respond sufficiently to other interventions.

There is a critical knowledge gap in optimally combining transcranial magnetic stimulation (TMS) and antidepressants to treat patients with major depressive disorder (MDD). TMS is effective in treating MDD in patients who have failed at least one antidepressant trial, with accelerated protocols showing faster remission in treatment-resistant depression (TRD). Although clinicians routinely augment antidepressants with TMS, there is a knowledge gap in stopping versus continuing antidepressants or the dosing strategies when starting or tapering TMS. These considerations are important when considering maintenance TMS (delivered alone or in combination with suitable antidepressants) to maintain remission in MDD after the index course of TMS. As the first step towards filling this knowledge gap, we reviewed randomized controlled trials (RCTs) and open-label trials from 2 databases (PubMed/Medline and EMBASE) that compared active TMS combined with a pre-specified antidepressant dosed in the same manner for adults with MDD versus sham TMS combined with the same antidepressant as in the active arm. All studies were published between January 1, 2000, and December 31, 2023. We excluded case reports, case series, and clinical studies that augmented TMS with antidepressants and vice versa. We found 10 RCTs (n = 654 participants) and performed a meta-analysis. This showed active TMS combined with pre-specified antidepressants had greater efficacy for MDD treatment than sham TMS combined with the same antidepressants as in the active arm (Hedge's g = 1; 95 % CI [0.27, 1.73]). The review and meta-analysis indicate greater short-term efficacy in combining antidepressants with TMS from the get-go in MDD. Given the increasing role of accelerated TMS protocols in expediting remission in MDD and the results of our meta-analysis, we advocate for RCTs examining the short-term and long-term effects of various antidepressant classes on these TMS protocols in MDD. This can also optimize and individualize maintenance TMS protocols to prevent relapse in MDD.

Electroconvulsive therapy (ECT) is one of the most effective psychiatric treatments but the underlying mechanisms are still unclear. In vivo human magnetic resonance imaging (MRI) studies have consistently reported ECT-induced transient hippocampal volume increases, and an animal model of ECT (electroconvulsive stimulation: ECS) was shown to increase neurogenesis. However, a causal relationship between neurogenesis and MRI-detectable hippocampal volume increases following ECT has not been verified. In this study, mice were randomly allocated into four groups, each undergoing a different number of ECS sessions (e.g., 0, 3, 6, 9). T2-weighted images were acquired using 11.7-tesla MRI. A whole brain voxel-based morphometry analysis was conducted to identify any ECS-induced brain volume changes. Additionally, a histological examination with super-resolution microscopy was conducted to investigate microstructural changes in the brain regions that showed volume changes following ECS. Furthermore, parallel experiments were performed on X-ray-irradiated mice to investigate the causal relationship between neurogenesis and ECS-related volume changes. As a result, we revealed for the first time that ECS induced MRI-detectable, dose-dependent hippocampal volume increase in mice. Furthermore, increased hippocampal volumes following ECS were seen even in mice lacking neurogenesis, suggesting that neurogenesis is not required for the increase. The comprehensive histological analyses identified an increase in excitatory synaptic density in the ventral CA1 as the major contributor to the observed hippocampal volume increase following ECS. Our findings demonstrate that modification of synaptic structures rather than neurogenesis may be the underlying biological mechanism of ECT/ECS-induced hippocampal volume increase.

There is no established treatment for patients with clozapine-resistant schizophrenia (CRS). Clozapine augmentation strategies with antipsychotics or others substances are effective in comparison with placebo while and Electroconvulsive therapy (ECT) showed to be effective in comparison with treatment as usual (TAU) but not with placebo (sham-ECT). In the present double- blind randomized controlled trial, we compared 40 outpatients who received 20 sessions of ECT (n = 21) or sham-ECT (n = 19) (age = 37.40 ± 9.62, males = 77.5 %, illness duration = 14.95 ± 8.32 years, mean total Positive and Negative Syndrome Scale (PANSS) = 101.10 ± 24.91) who fulfilled well-defined CRS criteria including baseline clozapine plasma levels ≥350 ng/mL. The primary outcome was the ≥50 % PANSS Total Score reduction; secondary outcomes were the scores of the PANSS subscales, PANSS five-factor dimensions, PANSS-6 and the Calgary Depression Rating Scale (CDRS). Treatment response was analyzed by percentage reduction, Linear Mixed Models and effect sizes. At baseline both groups showed no differences except for years of school education (included as a covariate). At endpoint, only 1/19 of the completers (5.26 %) in the ECT group and 0/17 in the sham-ECT group showed a ≥50 % total PANSS score reduction. Both groups showed no significant differences of the total PANSS score (F = 0.12; p = 0.73), Positive (F = 0.27, p = 0.61), Negative (F = 0.25, p = 0.62), and General Psychopathology scores (F = 0.01, p = 0.94) as well for all PANSS five factors, the PANSS-6 and CDRS. Thus, the present study found no evidence that ECT is better than Sham-ECT in patients with CRS. Future sham-ECT controlled studies with larger sample sizes are warranted to test the efficacy of ECT for patients with CRS.

Access to literature on clozapine in Russian language remains strikingly limited. We aimed to identify and translate clinical evidence on clozapine-based treatment outcomes.

We performed a systematic review in PubMed, Embase and scientific indexes from former USSR states searching for articles published in Russian from the database inception till January 2023 and summarized the data in a scoping review (PROSPERO Reg. Number CRD42023386737).

A total of 60 papers were included comprising eight main topic categories: 1) clozapine-related intoxications (n = 20), 2) effectiveness/efficacy and safety of clozapine treatment (n = 14), 3) adverse drug-induced reactions (ADRs) related to clozapine treatment (n = 9), 4) therapeutic drug monitoring for clozapine (n = 5), 5) combination of clozapine and non-pharmacological treatments (n = 4), 6) pharmacoepidemiology of clozapine (n = 3), 7) effects of clozapine on the brain electrical activity (n = 3), and 8) novel clozapine formulations (n = 2). Among clozapine-related intoxications there were reports of criminal poisoning, which was associated with low lethality. Worse outcomes were accompanied by systemic reactions to intoxications. Clinical benefits of hemoadsorption were reported in the management of clozapine-related intoxications. Only half of studies reporting clozapine effectiveness used standardized scales to assess outcomes. Clozapine superiority in treatment-resistant schizophrenia (TRS) was replicated in one trial. No reports of clozapine-related agranulocytosis were identified. Clozapine ranked among most prescribed antipsychotics for TRS and non-TRS.

As clinical research in former USSR states is advancing to adopt western clinical research standards, comparability and extrapolation of findings is expected to increase, with transfer of older findings to clinical practice being particularly challenging.

Despite a very high prevalence and substantial impairments among affected individuals, treatment-resistant schizophrenia (TRS) has not been sufficiently researched in clinical research in the field of psychiatric disorders and the pathophysiology is still poorly understood. A better clinical and pathophysiological understanding of this heterogeneous and severely affected population of people with persistent symptoms in different domains is necessary in order not only to be able to intervene early but also to develop novel therapeutic strategies or individualized treatment approaches. This review article presents the state of the art criteria of the pharmacological TRS, neurobiological disease models and predictive factors for TRS as well as the phenomenon of pseudo-treatment resistance and the clinical management of TRS. In the future, not only the use of operationalized criteria and definitions of TRS in longitudinal studies and randomized-controlled trials (RCTs) are paramount, but also the observation of trajectories with the integration of multimodal longitudinal phenotyping and the longitudinal collection of clinical routine data in academic research, which will be possible in the newly created German Center for Mental Health (DZPG).

Electroconvulsive therapy (ECT) is an effective treatment modality for schizophrenia. However, its antipsychotic-like mechanism remains unclear.

To gain insight into the antipsychotic-like actions of ECT, this study investigated how repeated treatments of electroconvulsive seizure (ECS), an animal model for ECT, affect the behavioral and transcriptomic profile of a neurodevelopmental animal model of schizophrenia.

Two injections of MK-801 or saline were administered to rats on postnatal day 7 (PN7), and either repeated ECS treatments (E10X) or sham shock was conducted daily from PN50 to PN59. Ultimately, the rats were divided into vehicle/sham (V/S), MK-801/sham (M/S), vehicle/ECS (V/E), and MK-801/ECS (M/E) groups. On PN59, prepulse inhibition and locomotor activity were tested. Prefrontal cortex transcriptomes were analyzed with mRNA sequencing and network and pathway analyses, and quantitative real-time polymerase chain reaction (qPCR) analyses were subsequently conducted.

Prepulse inhibition deficit was induced by MK-801 and normalized by E10X. In M/S vs. M/E model, Egr1, Mmp9, and S100a6 were identified as center genes, and interleukin-17 (IL-17), nuclear factor kappa B (NF-κB), and tumor necrosis factor (TNF) signaling pathways were identified as the three most relevant pathways. In the V/E vs. V/S model, mitophagy, NF-κB, and receptor for advanced glycation end products (RAGE) pathways were identified. qPCR analyses demonstrated that Igfbp6, Btf3, Cox6a2, and H2az1 were downregulated in M/S and upregulated in M/E.

E10X reverses the behavioral changes induced by MK-801 and produces transcriptional changes in inflammatory, insulin, and mitophagy pathways, which provide mechanistic insight into the antipsychotic-like mechanism of ECT.

Functional neuroimaging emerged with great promise and has provided fundamental insights into the neurobiology of schizophrenia. However, it has faced challenges and criticisms, most notably a lack of clinical translation. This paper provides a comprehensive review and critical summary of the literature on functional neuroimaging, in particular functional magnetic resonance imaging (fMRI), in schizophrenia. We begin by reviewing research on fMRI biomarkers in schizophrenia and the clinical high risk phase through a historical lens, moving from case-control regional brain activation to global connectivity and advanced analytical approaches, and more recent machine learning algorithms to identify predictive neuroimaging features. Findings from fMRI studies of negative symptoms as well as of neurocognitive and social cognitive deficits are then reviewed. Functional neural markers of these symptoms and deficits may represent promising treatment targets in schizophrenia. Next, we summarize fMRI research related to antipsychotic medication, psychotherapy and psychosocial interventions, and neurostimulation, including treatment response and resistance, therapeutic mechanisms, and treatment targeting. We also review the utility of fMRI and data-driven approaches to dissect the heterogeneity of schizophrenia, moving beyond case-control comparisons, as well as methodological considerations and advances, including consortia and precision fMRI. Lastly, limitations and future directions of research in the field are discussed. Our comprehensive review suggests that, in order for fMRI to be clinically useful in the care of patients with schizophrenia, research should address potentially actionable clinical decisions that are routine in schizophrenia treatment, such as which antipsychotic should be prescribed or whether a given patient is likely to have persistent functional impairment. The potential clinical utility of fMRI is influenced by and must be weighed against cost and accessibility factors. Future evaluations of the utility of fMRI in prognostic and treatment response studies may consider including a health economics analysis.

Schizophrenia is a debilitating neuropsychiatric disorder that affects approximately 1% of the population and poses a major public health problem. Despite over 100 years of study, the treatment for schizophrenia remains limited, partially due to the lack of knowledge about the neural mechanisms of the illness and how they relate to symptoms. The US Food and Drug Administration (FDA) and the National Institute of Health (NIH) have provided seven biomarker categories that indicate causes, risks, and treatment responses. However, no FDA-approved biomarkers exist for psychiatric conditions, including schizophrenia, highlighting the need for biomarker development. Over three decades, magnetic resonance imaging (MRI)-based studies have identified patterns of abnormal brain function in schizophrenia. By using functional connectivity (FC) data, which gauges how brain regions interact over time, these studies have differentiated patient subgroups, predicted responses to antipsychotic medication, and correlated neural changes with symptoms. This suggests FC metrics could serve as promising biomarkers. Here, we present a selective review of studies leveraging MRI-derived FC to study neural alterations in schizophrenia, discuss how they align with FDA-NIH biomarkers, and outline the challenges and goals for developing FC biomarkers in schizophrenia.

Electroconvulsive therapy (ECT) is the most effective antidepressant treatment, although its mechanisms of action remain unclear. Since 2010, several structural magnetic resonance imaging studies based on a neuroplastic hypothesis have consistently reported increases in the hippocampal volume following ECT. Moreover, volume increases in the human dentate gyrus, where neurogenesis occurs, have also been reported. These results are in line with the preclinical findings of ECT-induced neuroplastic changes, including neurogenesis, gliogenesis, synaptogenesis, and angiogenesis, in rodents and nonhuman primates. Despite this robust evidence of an effect of ECT on hippocampal plasticity, the clinical relevance of these human hippocampal changes continues to be questioned. This narrative review summarizes recent findings regarding ECT-induced hippocampal volume changes. Furthermore, this review also discusses methodological considerations and future directions in this field.

Transcranial magnetic stimulation (TMS) can offer therapeutic benefits and provide value in neurophysiological research. One of the newer TMS paradigms is theta burst stimulation (TBS) which can be delivered in two patterns: continuous (cTBS - inducing LTD-like effects) and intermittent (iTBS - inducing LTP-like effects). This review paper aims to explore studies that have utilized TBS protocols over different areas of the cortex to study the neurophysiological functions and treatment of patients with schizophrenia. PubMed was searched using the following keywords "schizophrenia", "schizoaffective", or "psychosis", and "theta burst stimulation". Out of the 90 articles which were found, thirty met review inclusion criteria. The inclusion criteria included studying the reported effect (clinical, physiological, or both) of at least one session of TBS on human subjects, and abstracts (at minimum) must have been in English. The main target areas included prefrontal cortex (12 studies - 10 dorsolateral prefrontal cortex (DLPFC), 2 dorsomedial prefrontal cortex (DMPFC)) vermal cerebellum (5), and temporo-parietal cortex (8). Other target areas included inferior parietal lobe (2), and motor cortex (3). TBS neurophysiological effect was explored in 5 studies using functional magnetic resonance image (fMRI), magnetic resonance spectroscopy (MRS), electroencephalography (EEG), electromyography (EMG) and positron emission topography (PET) scan. Overall, TBS can offer great therapeutic potential as it is well-tolerated, feasible, and has few, if any, adverse effects. TBS may be targeted to treat specific symptomatology, as an augmenting intervention to pharmacotherapy, or even improving patient's insight into their diagnosis.

Electroconvulsive therapy (ECT) is a widely used therapeutic option of drug-refractory psychiatric disorders. ECT treats psychiatric symptoms by inducing brief controlled seizures through electrical stimulation, but ECT does not generally cause prolonged seizures or epilepsy. However, several studies have reported cases of prolonged seizures after ECT. This review aimed to determine the mechanism of epileptogenesis with neurobiological changes after ECT. Contrary to epileptogenesis by ECT, several cases have reported that ECT was successfully applied for treatment of refractory status epilepticus. In addition, ECT might be applied to hyperkinetic movement and psychiatric symptoms of encephalitis. We also investigated the anticonvulsant mechanism of ECT and how it controls encephalitis symptoms.

The main aim of this systematic review and meta-analysis is to establish whether there is a correlation between the brain-derived neurotrophic factor (BDNF) level and electroconvulsive therapy (ECT) treatment and the reduction in psychotic symptoms in patients diagnosed with schizophrenia. A systematic search of PubMed/Medline, Cochrane Library, Web of Science, Scopus and Embase was conducted up to March 2023. Inclusion criteria: studies in which adult patients with schizophrenia treated with antipsychotic medication received ECT therapy and had the BDNF level measured before and after ECT treatment. Exclusion criteria: animal and in vitro studies or studies not involving complete information about the treatment and concentration of BDNF in plasma. The risk of bias was assessed using Egger's regression-based test for meta-analysis with continuous outcomes. Six studies comprising 248 individuals with schizophrenia were included. A statistically significant increase in BDNF levels after ECT treatment was observed only in two studies (p < 0.001 and p < 0.027, respectively), whereas in four other studies, an upward trend without statistical significance was noticed. The estimated overall size effect revealed that ECT therapy caused a slight change in the BDNF level but without statistical significance (ES = -0.328). Different numbers of ECT procedures (4-10), final measurement of the BDNF level made at a different time point, using bilateral or unilateral electrode positioning during ECT and treatment with different combinations of typical or atypical antipsychotic medications may be potential reasons for the lack of statistical significance in the changes in BDNF levels after treatment. Data regarding the measurement of BDNF levels pre and post ECT therapy in patients with schizophrenia are very limited without an extended follow-up period and evaluation of mental health change. Our meta-analysis showed that treatment with ECT therapy and antipsychotic medication increases serum BDNF levels in patients with drug-resistant schizophrenia compared to patients treated with medication only; however, this effect is not statistically significant.

This study sought to compare pre-intervention patient characteristics and post-intervention outcomes in a naturalistic sample of adolescent inpatients with treatment-resistant psychotic symptoms who received either electroconvulsive therapy (ECT) or clozapine.

Data of adolescents with schizophrenia/schizoaffective disorder receiving ECT or clozapine were retrospectively collected from two tertiary-care psychiatry-teaching university hospitals. Subscale scores of the Positive and Negative Symptom Scale (PANSS) factors were calculated according to the five-factor solution. Baseline demographics, illness characteristics, and post-intervention outcomes were compared.

There was no significant difference between patients receiving ECT (n = 13) and clozapine (n = 66) in terms of age, sex, and the duration of hospital stay. The ECT group more commonly had higher overall illness and aggression severity. Smoking was less frequent in the clozapine group. Baseline resistance/excitement symptom severity was significantly higher in the ECT group, while positive, negative, affect, disorganisation, and total symptom scores were not. Both interventions provided a significant reduction in PANSS scores with large effect sizes.

Both ECT and clozapine yielded high effectiveness rates in adolescents with treatment-resistant schizophrenia/schizoaffective disorder. Youth receiving ECT were generally more activated than those who received clozapine.

Treatment-resistant symptoms occur in about a third of patients with schizophrenia and are associated with a substantial reduction in their quality of life. The development of new treatment options for clozapine-resistant schizophrenia constitutes a crucial, unmet need in psychiatry. Additionally, an overview of past and possible future research avenues to optimise the early detection, diagnosis, and management of clozapine-resistant schizophrenia is unavailable. In this Health Policy, we discuss the ongoing challenges associated with clozapine-resistant schizophrenia faced by patients and health-care providers worldwide to improve the understanding of this condition. We then revisit several clozapine guidelines, the diagnostic tests and treatment options for clozapine-resistant schizophrenia, and currently applied research approaches in clozapine-resistant schizophrenia. We also suggest methodologies and targets for future research, divided into innovative nosology-oriented field trials (eg, examining dimensional symptom staging), translational approaches (eg, genetics), epidemiological research (eg, real-world studies), and interventional studies (eg, non-traditional trial designs incorporating lived experiences and caregivers' perspectives). Finally, we note that low-income and middle-income countries are under-represented in studies on clozapine-resistant schizophrenia and propose an agenda to guide multinational research on the cause and treatment of clozapine-resistant schizophrenia. We hope that this research agenda will empower better global representation of patients living with clozapine-resistant schizophrenia and ultimately improve their functional outcomes and quality of life.

Early prediction of treatment response to antipsychotics in schizophrenia remains a challenge in clinical practice. This study aimed to investigate if brain morphometries including gray matter volume and cortical thickness could serve as potential predictive biomarkers in first-episode schizophrenia.

Sixty-eight drug-naïve first-episode patients underwent baseline structural MRI scans and were subsequently randomized to receive a single antipsychotic throughout the first 12 weeks. Assessments for symptoms and social functioning were conducted by eight "core symptoms" selected from the Positive and Negative Syndrome Scale (PANSS-8) and the Personal and Social performance scale (PSP) multiple times during follow-ups. Treatment outcome was evaluated as subject-specific slope coefficients for PANSS-8 and PSP scores using linear mixed model. LASSO regression model were conducted to examine the performance of baseline gray matter volume and cortical thickness in prediction of individualized treatment outcome.

The study showed that individual brain morphometries at baseline, especially the orbitofrontal, temporal and parietal cortex, pallidum and amygdala, significantly predicted 12-week treatment outcome of PANSS-8 (r[predicted vs observed] = 0.49, P = .001) and PSP (r[predicted vs observed] = 0.40, P = .003) in first-episode schizophrenia. Moreover, the gray matter volume performed better than cortical thickness in the prediction the symptom changes (P = .034), while cortical thickness outperformed gray matter volume in the prediction of outcome of social functioning (P = .029).

These findings provide initial evidence that brain morphometry have potential to be used as prognostic predictors for antipsychotic response in patients, encouraging the future investigation of the translational value of these measures in precision psychiatry.

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.

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.

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.

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.

Several augmentation strategies have been used to improve symptomatology in patients not adequately responding to clozapine. Several randomised controlled trials (RCTs) have evaluated the efficacy of different strategies to augment clozapine. This systematic review and meta-analysis reviewed the available RCTs that have evaluated the clinical efficacy of various pharmacological agents, non-pharmacological strategies (occupational therapy, cognitive behaviour therapy), and somatic treatment [electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation, etc.)] as augmenting agents to clozapine.

Data were extracted using standard procedures, and risk of bias was evaluated. Effect sizes were computed for the individual studies.

Forty-five clinical trials were evaluated. The pooled effect size for various antipsychotic medications was 0.103 (95% CI: 0.288-0.493, p < 0.001); when the effect size was evaluated for specific antipsychotics for which more than one trial was available, the effect size for risperidone was -0.27 and that for aripiprazole was 0.57. The effect size for lamotrigine was 0.145, and that for topiramate was 0.392. The effect size for ECT was 0.743 (CI: 0.094-1.392). Risk of bias was low (mean Jadad score - 3.93). Largest effect sizes were seen for mirtazapine (effect size of 5.265). Most of the studies can be considered underpowered and limited by small sample sizes.

To conclude, based on the findings of the present systematic review and meta-analysis, it can be said that compared to other treatment strategies, clozapine non-responsive patients respond maximum to mirtazapine followed by ECT.

It is unknown whether increasing the clozapine plasma level to 400, 750, or even 1000 ng/mL is a feasible and effective strategy in patients with treatment-resistant schizophrenia (TRS). We investigated this in long-stay patients with TRS.

In long-stay TRS patients, doses of clozapine were increased gradually to reach target plasma levels of 400, 750, or 1000 ng/mL, depending on the clinical response and tolerability. After an effective or tolerated level was reached, positive and negative syndrome scale scores were evaluated after 3 months and 1 year.

Twenty-eight patients were included. Overall, 54% of the patients, and especially patients 60 years and older, could not achieve one of the clozapine target levels because of adverse effects. Three physically vulnerable patients died, probably not directly related to clozapine use. Although only 21% of patients achieved a more than 20% reduction in total symptoms at the 1-year follow-up, the mean severity of positive symptoms decreased from 18.18 to 15.10 ( P < 0.01). The largest decrease in positive symptoms was seen in TRS patients who achieved a plasma level of 750 ng/mL of clozapine.

Most TRS patients older than 60 years could not tolerate high clozapine levels and so this should not be attempted in older or otherwise physically vulnerable patients. Increasing clozapine levels to approximately 750 ng/mL in middle-aged patients with longstanding TRS may modestly reduce the severity of positive symptoms and improve the response rate.

The study aimed to investigate the effectiveness of maintenance electroconvulsive therapy (mECT) with respect to the hospitalization duration, number of hospitalizations, and major and minor treatment changes with a mirror-image study design.

Medical charts of patients who received at least a 3-month-long course of mECT were reviewed. The records of 36 patients (17 with psychotic disorders, 19 with affective disorders) were retrospectively examined for 2 periods with the same duration; during the mECT (post-mECT) and before the mECT (pre-mECT). The hospitalization duration, the number of hospitalizations, and major and minor treatment changes, which were assumed to provide information on the effectiveness of the interventions, were recorded and compared between these periods. Statistical analysis was performed using generalized estimating equation models conducted with age, diagnostic category, and observation time as covariates. In addition, the relapse and recurrence rates and time to relapse/recurrence were analyzed.

Comparison of pre-mECT and post-mECT periods revealed that mECT, applied in an individualized schedule combined with pharmacotherapy, was associated with a lower frequency ( P < 0.001; rate ratio [RR], 0.161; 95% confidence interval [CI], 0.087-0.297), shorter duration of hospitalization ( P < 0.001; RR, 0.123; 95% CI, 0.056-0.271), and lower number of major treatment changes ( P = 0.007; RR, 0.522; 95% CI, 0.324-0.840), irrespective of diagnoses. The relapse/recurrence rates were similar in the 2 diagnostic categories ( P = 1.000; 26.3% vs 29.4%).

Maintenance ECT should be increasingly considered an important treatment modality in patients with affective and psychotic disorders after an effective course of ECT.

To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for clozapine-resistant schizophrenia (CRS).

Six major electronic databases were systematically searched for RCTs published until July 10, 2021. The primary outcome was change in overall symptoms, and the secondary outcomes were positive and negative symptoms and acceptability. We performed random-effects network meta-analysis. Normalized entropy was calculated to examine the uncertainty of treatment ranking.

We identified 35 RCTs (1472 patients with 23 active augmentation treatments) with a mean daily clozapine dose of 440.80 (91.27) mg for 1168.22 (710.28) days. Network meta-analysis of overall symptoms (reported as standardized mean difference; 95 % confidence interval) with consistent results indicated that mirtazapine (-4.41; -5.61, -3.21), electroconvulsive therapy (ECT) (-4.32; -5.43, -3.21), and memantine (-2.02; -3.14, -0.91) were ranked as the best three treatments. For positive symptoms, ECT (-5.18; -5.86, -4.49) was ranked the best with less uncertainty. For negative symptoms, memantine (-3.38; -4.50, -2.26), duloxetine (-3.27; -4.25, -2.29), and mirtazapine (-1.73; -2.71, -0.74) were ranked the best three treatments with less uncertainty. All antipsychotics, N-methyl d-aspartate receptor agonists, and antiepileptics were not associated with more efficacy than placebo. Compared to placebo, only amisulpride had statistically significant lower discontinuation rate (risk ratio: 0.21; 95 % CI: 0.05, 0.93).

Add-on mirtazapine, ECT, and memantine were the most efficacious augmentation options for CRS. Data on other important outcomes such as cognitive functioning or quality of life were rarely reported, making further large-scale, well-designed RCTs necessary. (PROSPERO number, CRD42021262197.).

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.

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.

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.

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.

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.

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.

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.

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.

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.

Background: A substantial proportion of patients with treatment resistant schizophrenia do not respond well or partially to clozapine, with a subset that does not tolerate an adequate trial of clozapine. Electroconvulsive therapy (ECT) is regarded as one of the augmenting options, but there is a lack of high-quality evidence for this practice. This protocol describes a double-blind randomised sham-controlled modified-ECT trial to evaluate its efficacy in patients with clozapine resistant/intolerant schizophrenia. The study also involves multimodal investigations to identify the response predictors and the mechanistic basis of modified ECT in this population. Methods: One hundred consenting schizophrenia patients with resistance/intolerance to clozapine referred by clinicians for ECT would be randomly assigned to receive true ECT or sham ECT at three study centers. Sham ECT would mimic all the procedures of modified ECT including anaesthesia and muscle relaxation, except the electrical stimulation. After a blinded course, non-responders to sham ECT would be offered open-label true ECT. Clinical assessments, neurocognitive assessments and multimodal investigations (magnetic resonance imaging [MRI], electroencephalography, heart rate variability, investigative transcranial magnetic stimulation-transcranial direct current stimulation, gene polymorphism) would be conducted at baseline and repeated after the end of the trial, as well as open-label ECT course. The trial would evaluate the improvement in positive symptoms (scale for assessment of positive symptoms) of schizophrenia as the primary outcome measure with prediction of this change by resting-state functional-MRI based brain-connectivity as the second primary objective. Registration: Clinical Trial Registry of India (Reg no: CTRI/2021/05/033775) on 24 th May 2021.