Electroconvulsive therapy and cognitive performance from the Global ECT MRI Research Collaboration.

The Global ECT MRI Research Collaboration (GEMRIC) has collected clinical and neuroimaging data of patients treated with electroconvulsive therapy (ECT) from around the world. Results to date have focused on neuroimaging correlates of antidepressant response. GEMRIC sites have also collected longitudinal cognitive data. Here, we summarize the existing GEMRIC cognitive data and provide recommendations for prospective data collection for future ECT-imaging investigations. We describe the criteria for selection of cognitive measures for mega-analyses: Trail Making Test Parts A (TMT-A) and B (TMT-B), verbal fluency category (VFC), verbal fluency letter (VFL), and percent retention from verbal learning and memory tests. We performed longitudinal data analysis focused on the pre-/post-ECT assessments with healthy comparison (HC) subjects at similar timepoints and assessed associations between demographic and ECT parameters with cognitive changes. The study found an interaction between electrode placement and treatment number for VFC (F(1,107) = 4.14, p = 0.04). Higher treatment was associated with decreased VFC performance with right unilateral electrode placement. Percent retention showed a main effect for group, with post-hoc analysis indicating decreased cognitive performance among the HC group. However, there were no significant effects of group or group interactions observed for TMT-A, TMT-B, or VFL. We assessed the current GEMRIC cognitive data and acknowledge the limitations associated with this data set including the limited number of neuropsychological domains assessed. Aside from the VFC and treatment number relationship, we did not observe ECT-mediated neurocognitive effects in this investigation. We provide prospective cognitive recommendations for future ECT-imaging investigations focused on strong psychometrics and minimal burden to subjects.

Exploring postictal recovery with acetaminophen or nimodipine: A randomized-controlled crossover trial.

OBJECTIVE: The postictal state is underrecognized in epilepsy. Animal models show improvement of postictal symptoms and cerebral perfusion with acetaminophen or nimodipine. We studied the effects of acetaminophen or nimodipine on postictal electroencephalographic (EEG) recovery, clinical reorientation, and hypoperfusion in patients with ECT-induced seizures. METHODS: In this prospective clinical trial with three-condition randomized crossover design, study interventions were administered orally 2 h before ECT sessions (1000 mg acetaminophen, 60 mg nimodipine, or a placebo condition). Primary outcome measure was the speed of postictal EEG recovery. Secondary outcomes were the extent of postictal EEG recovery, clinical reorientation time, and postictal cerebral blood flow as assessed by perfusion-weighted MRI. Bayesian generalized mixed-effects models were applied for analyses. RESULTS: We included 300 seizures, postictal EEGs, and reorientation time values, and 76 MRI perfusion measures from 33 patients (median age 53 years, 19 female). Pretreatment with acetaminophen or nimodipine was not associated with change in speed of EEG recovery compared to placebo (1.13 [95%CI 0.92, 1.40] and 1.07 [95%CI 0.87, 1.31], respectively), nor with the secondary outcomes. No patient reached full EEG recovery at 1 h post-seizure, despite clinical recovery in 89%. Longer seizures were associated with slower EEG recovery and lower postictal perfusion. Nimodipine altered regional perfusion in the posterior cortex. INTERPRETATION: Pretreatment with acetaminophen or nimodipine did not alleviate symptoms and signs of the postictal state. Systematic study of the postictal state after ECT-induced seizures is feasible.

Characterization of gray matter volume changes from one week to 6 months after termination of electroconvulsive therapy in depressed patients.

BACKGROUND: Increased gray matter volume (GMV) following electroconvulsive therapy (ECT) has been well-documented, with limited studies reporting a subsequent decrease in GMV afterwards. OBJECTIVE: This study characterized the reversion pattern of GMV after ECT and its association with clinical depression outcome, using multi-site triple time-point data from the Global ECT-MRI Research Collaboration (GEMRIC). METHODS: 86 subjects from the GEMRIC database were included, and GMV in 84 regions-of-interest (ROI) was obtained from automatic segmentation of T1 MRI images at three timepoints: pre-ECT (T0), within one-week post-ECT (T1), and one to six months post-ECT (T2). RM-ANOVAs were used to assess longitudinal changes and LMM analyses explored associations between GMV changes and demographical and clinical characteristics. RESULTS: 63 of the 84 ROIs showed a significant increase-and-decrease pattern (RM-ANOVA, Bonferroni corrected p < 0.00059). Post hoc tests indicated a consistent pattern in each of these 63 ROIs: significant increase from T0 to T1inGMV, followed by significant decrease from T1 to T2 and no difference between T0 and T2, except for both amygdalae, right hippocampus and pars triangularis, which showed the same increase and decrease but GMV at T2 remained higher compared to T0. No consistent relationship was found between GMV change pattern and clinical status. CONCLUSION: The GEMRIC cohort confirmed a rapid increase of GMV after ECT followed by reversion of GMV one to six months thereafter. The lack of association between the GMV change pattern and depression outcome scores implies a transient neurobiological effect of ECT unrelated to clinical improvement.

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.

Development and validation of a multimodal neuroimaging biomarker for electroconvulsive therapy outcome in depression: a multicenter machine learning analysis.

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective intervention for patients with treatment resistant depression. A clinical decision support tool could guide patient selection to improve the overall response rate and avoid ineffective treatments with adverse effects. Initial small-scale, monocenter studies indicate that both structural magnetic resonance imaging (sMRI) and functional MRI (fMRI) biomarkers may predict ECT outcome, but it is not known whether those results can generalize to data from other centers. The objective of this study was to develop and validate neuroimaging biomarkers for ECT outcome in a multicenter setting. METHODS: Multimodal data (i.e. clinical, sMRI and resting-state fMRI) were collected from seven centers of the Global ECT-MRI Research Collaboration (GEMRIC). We used data from 189 depressed patients to evaluate which data modalities or combinations thereof could provide the best predictions for treatment remission (HAM-D score ⩽7) using a support vector machine classifier. RESULTS: Remission classification using a combination of gray matter volume and functional connectivity led to good performing models with average 0.82-0.83 area under the curve (AUC) when trained and tested on samples coming from the three largest centers (N = 109), and remained acceptable when validated using leave-one-site-out cross-validation (0.70-0.73 AUC). CONCLUSIONS: These results show that multimodal neuroimaging data can be used to predict remission with ECT for individual patients across different treatment centers, despite significant variability in clinical characteristics across centers. Future development of a clinical decision support tool applying these biomarkers may be feasible.

Changes in postictal cerebral perfusion are related to the duration of electroconvulsive therapy-induced seizures.

OBJECTIVE: Postictal symptoms may result from cerebral hypoperfusion, which is possibly a consequence of seizure-induced vasoconstriction. Longer seizures have previously been shown to cause more severe postictal hypoperfusion in rats and epilepsy patients. We studied cerebral perfusion after generalized seizures elicited by electroconvulsive therapy (ECT) and its relation to seizure duration. METHODS: Patients with a major depressive episode who underwent ECT were included. During treatment, 21-channel continuous electroencephalogram (EEG) was recorded. Arterial spin labeling magnetic resonance imaging scans were acquired before the ECT course (baseline) and approximately 1 h after an ECT-induced seizure (postictal) to quantify global and regional gray matter cerebral blood flow (CBF). Seizure duration was assessed from the period of epileptiform discharges on the EEG. Healthy controls were scanned twice to assess test-retest variability. We performed hypothesis-driven Bayesian analyses to study the relation between global and regional perfusion changes and seizure duration. RESULTS: Twenty-four patients and 27 healthy controls were included. Changes in postictal global and regional CBF were correlated with seizure duration. In patients with longer seizure durations, global decrease in CBF reached values up to 28 mL/100 g/min. Regional reductions in CBF were most prominent in the inferior frontal gyrus, cingulate gyrus, and insula (up to 35 mL/100 g/min). In patients with shorter seizures, global and regional perfusion increased (up to 20 mL/100 g/min). These perfusion changes were larger than changes observed in healthy controls, with a maximum median global CBF increase of 12 mL/100 g/min and a maximum median global CBF decrease of 20 mL/100 g/min. SIGNIFICANCE: Seizure duration is a key factor determining postictal perfusion changes. In future studies, seizure duration needs to be considered as a confounding factor due to its opposite effect on postictal perfusion.

Longitudinal resting-state network connectivity changes in electroconvulsive therapy patients compared to healthy controls.

OBJECTIVE: Electroconvulsive therapy (ECT) is effective for major depressive episodes. Understanding of underlying mechanisms has been increased by examining changes of brain connectivity but studies often do not correct for test-retest variability in healthy controls (HC). In this study, we investigated changes in resting-state networks after ECT in a multicenter study. METHODS: Functional resting-state magnetic resonance imaging data, acquired before start and within one week after ECT, from 90 depressed patients were analyzed, as well as longitudinal data of 24 HC. Group-information guided independent component analysis (GIG-ICA) was used to spatially restrict decomposition to twelve canonical resting-state networks. Selected networks of interest were the default mode network (DMN), salience network (SN), and left and right frontoparietal network (LFPN, and RFPN). Whole-brain voxel-wise analyses were used to assess group differences at baseline, group by time interactions, and correlations with treatment effectiveness. In addition, between-network connectivity and within-network strengths were computed. RESULTS: Within-network strength of the DMN was lower at baseline in ECT patients which increased after ECT compared to HC, after which no differences were detected. At baseline, ECT patients showed lower whole-brain voxel-wise DMN connectivity in the precuneus. Increase of within-network strength of the LFPN was correlated with treatment effectiveness. We did not find whole-brain voxel-wise or between-network changes. CONCLUSION: DMN within-network connectivity normalized after ECT. Within-network increase of the LFPN in ECT patients was correlated with higher treatment effectiveness. In contrast to earlier studies, we found no whole-brain voxel-wise changes, which highlights the necessity to account for test-retest effects.

Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression.

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this causal depression network (CDN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis Principal Component Analysis (PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CDN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CDN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes (t = -2.35, p = 0.019). This evidence further supports that treatment interventions converge on a CDN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.

A Multicenter Retrospective Chart Review on the Effectiveness and Tolerability of Electroconvulsive Therapy in Adolescents and Young Adults With Major Depressive Disorder or Bipolar Depression.

BACKGROUND: Major depressive disorder and bipolar depression in adolescents and young adults are prevalent and major contributors to the global burden of disease, whereas effective interventions are limited. Available evidence is insufficient to assess effectiveness and tolerability of electroconvulsive therapy in depressed adolescents and young adults. METHODS: A retrospective chart review was conducted in patients with major depressive disorder or bipolar depression who underwent electroconvulsive therapy from 2001 to 2021 in 12 centers in the Netherlands. Patients were classified as young (15-25 years) and older adults (26-80 years). Primary outcome was effectiveness, expressed as response (≥50% reduction in rating scale score compared with baseline) and remission. Rating scale scores were cross-sectionally assessed at baseline and at the end of the index course. Outcomes of remitters were included in responders. Secondary outcome was occurrence of subjective cognitive impairment and adverse events. Long-term outcomes were not available. RESULTS: In the young (n = 57) and older adult (n = 41) group, 40.4% and 56.1% (P = 0.153) of patients achieved response and 28.1% and 39.0% (P = 0.281) remission, respectively. Subjective cognitive impairment (80.5% vs 56.3%; P = 0.001) and transient cardiac arrhythmia (14.6% vs 2.8%; P = 0.020) were reported significantly more frequently in the older adult group. CONCLUSIONS: Despite significantly more comorbidity of personality disorders, autism spectrum disorders, and anxiety disorders, effectiveness in the young was similar to the older adults. Tolerability was even superior in the young, despite significantly more bilateral treatment. Electroconvulsive therapy could be considered a viable treatment option in depressed adolescents and young adults.

Cortical excitation/inhibition ratios in patients with major depression treated with electroconvulsive therapy: an EEG analysis.

Electroconvulsive therapy (ECT) is an effective treatment for major depression, but its working mechanisms are poorly understood. Modulation of excitation/inhibition (E/I) ratios may be a driving factor. Here, we estimate cortical E/I ratios in depressed patients and study whether these ratios change over the course of ECT in relation to clinical effectiveness. Five-minute resting-state electroencephalography (EEG) recordings of 28 depressed patients were recorded before and after their ECT course. Using a novel method based on critical dynamics, functional E/I (fE/I) ratios in the frequency range of 0.5-30 Hz were estimated in frequency bins of 1 Hz for the whole brain and for pre-defined brain regions. Change in Hamilton Depression Rating Scale (HDRS) score was used to estimate clinical effectiveness. To account for test-retest variability, repeated EEG recordings from an independent sample of 31 healthy controls (HC) were included. At baseline, no differences in whole brain and regional fE/I ratios were found between patients and HC. At group level, whole brain and regional fE/I ratios did not change over the ECT course. However, in responders, frontal fE/I ratios in the frequencies 12-28 Hz increased significantly (pFDR < 0.05 [FDR = false discovery rate]) over the ECT course. In non-responders and HC, no changes occurred over time. In this sample, frontal fE/I ratios increased over the ECT course in relation to treatment response. Modulation of frontal fE/I ratios may be an important mechanism of action of ECT.

Rostral Anterior Cingulate Cortex Oscillatory Power Indexes Treatment-Resistance to Multiple Therapies in Major Depressive Disorder.

INTRODUCTION: High rostral anterior cingulate cortex (rACC) activity is proposed as a nonspecific prognostic marker for treatment response in major depressive disorder, independent of treatment modality. However, other studies report a negative association between baseline high rACC activation and treatment response. Interestingly, these contradictory findings were also found when focusing on oscillatory markers, specifically rACC-theta power. An explanation could be that rACC-theta activity dynamically changes according to number of previous treatment attempts and thus is mediated by level of treatment-resistance. METHODS: Primarily, we analyzed differences in rACC- and frontal-theta activity in large national cross-sectional samples representing various levels of treatment-resistance and resistance to multimodal treatments in depressed patients (psychotherapy [n = 175], antidepressant medication [AD; n = 106], repetitive transcranial magnetic stimulation [rTMS; n = 196], and electroconvulsive therapy [ECT; n = 41]), and the respective difference between remitters and non-remitters. For exploratory purposes, we also investigated other frequency bands (delta, alpha, beta, gamma). RESULTS: rACC-theta activity was higher (p < 0.001) in the more resistant rTMS and ECT patients relative to the less resistant psychotherapy and AD patients (psychotherapy-rTMS: d = 0.315; AD-rTMS: d = 0.320; psychotherapy-ECT: d = 1.031; AD-ECT: d = 1.034), with no difference between psychotherapy and AD patients. This association was even more pronounced after controlling for frontal-theta. Post hoc analyses also yielded effects for delta, beta, and gamma bands. CONCLUSION: Our findings suggest that by factoring in degree of treatment-resistance during interpretation of the rACC-theta biomarker, its usefulness in treatment selection and prognosis could potentially be improved substantially in future real-world practice. Future research should however also investigate specificity of the theta band.

[IV esketamine for patients with a treatment-resistant depression]. / Intraveneuze esketamine als redmiddel bij depressie.

We present three patients off-label treated with intravenous (IV) esketamine for treatment-resistant depression (TRD) of whom two (patients A and B, aged 72 and 77 years, respectively) were admitted to the psychiatric unit with depressive symptoms and one outpatient (patient C, aged 66 years). After six esketamine treatments over a period of three weeks, two patients showed improvement, as measured with the Hamilton Rating Scale for Depression (HRSD): the HRSD-score of patient A decreased from 36 to 9 and of patient C from 18 to 10. Patient B had no response to esketamine but was treated successfully with electroconvulsive therapy (ECT). Despite the presence of various somatic comorbidities, esketamine treatment appeared safe and well-tolerated by the patients. After the index treatment, patients A and C received maintenance treatment with esketamine (once every 4-6 weeks). We recommend to consider off-label IV esketamine treatment in patients suffering TRD with or without suicidality.

[Consider (es)ketamine for treatment-resistant depression]. / Overweeg (es)ketamine bij therapieresistente depressie.

Major depressive disorder has a high prevalence globally. Although pharmacotherapy and psychotherapy are effective for most patients, about one third is treatment resistant. Ketamine, known as an anesthetic, is a new treatment option that can be effective in patients with treatment-resistant depression. (es)ketamine works relatively fast. However, the long-term effects are still relatively unknown. In the Netherlands, S-Ketamine is currently administered in various forms, of which only the nasal spray is registered for treatment-resistant depression. Currently, many studies have been conducted on the use of (es)ketamine. In this article we describe the latest state of affairs regarding its effectiveness and safety.

Effective resting-state connectivity in severe unipolar depression before and after electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depressive disorders. A recent multi-center study found no consistent changes in correlation-based (undirected) resting-state connectivity after ECT. Effective (directed) connectivity may provide more insight into the working mechanism of ECT. OBJECTIVE: We investigated whether there are consistent changes in effective resting-state connectivity. METHODS: This multi-center study included data from 189 patients suffering from severe unipolar depression and 59 healthy control participants. Longitudinal data were available for 81 patients and 24 healthy controls. We used dynamic causal modeling for resting-state functional magnetic resonance imaging to determine effective connectivity in the default mode, salience and central executive networks before and after a course of ECT. Bayesian general linear models were used to examine differences in baseline and longitudinal effective connectivity effects associated with ECT and its effectiveness. RESULTS: Compared to controls, depressed patients showed many differences in effective connectivity at baseline, which varied according to the presence of psychotic features and later treatment outcome. Additionally, effective connectivity changed after ECT, which was related to ECT effectiveness. Notably, treatment effectiveness was associated with decreasing and increasing effective connectivity from the posterior default mode network to the left and right insula, respectively. No effects were found using correlation-based (undirected) connectivity. CONCLUSIONS: A beneficial response to ECT may depend on how brain regions influence each other in networks important for emotion and cognition. These findings further elucidate the working mechanisms of ECT and may provide directions for future non-invasive brain stimulation research.

Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression.

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this common causal network (CCN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis (Principal Component Analysis, PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CCN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CCN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes. This evidence further supports that treatment interventions converge on a CCN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.

Medication preventing postictal hypoperfusion and cognitive side-effects in electroconvulsive therapy: A retrospective cohort study.

Background: Electroconvulsive therapy (ECT) is associated with postictal confusion and cognitive side-effects. In rats, acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs) and calcium antagonists decreased postictal cerebral hypoperfusion along with reduction in postictal symptoms. In this study, in ECT-patients, we explore associations between use of these potentially protective medications and occurrence of postictal confusion and cognitive outcome. Materials and methods: In this retrospective, naturalistic cohort study, patient-, treatment-, and ECT-characteristics, were collected from medical files of patients treated with ECT for major depressive disorder (MDD) or bipolar depressive episode. To test for associations of use of these medications with occurrence of postictal confusion, 295 patients could be included. Cognitive outcome data were available in a subset of 109 patients. Univariate analyses and multivariate censored regression models were used to test for associations. Results: Occurrence of severe postictal confusion was not associated with use of acetaminophen, NSAIDs or calcium antagonists (n = 295). Regarding the cognitive outcome measure (n = 109), use of calcium antagonists was associated with higher post-ECT cognitive scores (i.e., better cognitive outcome; ß = 2.23; p = 0.047), adjusted for age (ß = -0.02; p = 0.23), sex (ß = -0.21; p = 0.73), pre-ECT cognitive score (ß = 0.47; p < 0.0001), and post-ECT depression score (ß = -0.02; p = 0.62), but use of acetaminophen (ß = -1.55; p = 0.07) as well as NSAIDs (ß = -1.02; p = 0.23) showed no associations. Conclusion: This retrospective study does not find arguments for protective effects of acetaminophen, NSAIDs or calcium antagonists against severe postictal confusion in ECT. As a preliminary finding, the use of calcium antagonists was associated with improved cognitive outcome after ECT in this cohort. Prospective controlled studies are necessary.

Severe Postictal Confusion After Electroconvulsive Therapy: A Retrospective Study.

OBJECTIVES: Severe postictal confusion (sPIC) is an important but poorly investigated adverse effect of electroconvulsive therapy (ECT). In this retrospective study, prevalence of sPIC and potential risk factors were explored. METHODS: Medical charts of 295 ECT patients (mean ± SD age, 57 ± 15 years; male, 36%) were scrutinized for occurrence of sPIC, as well as demographic, clinical, and treatment characteristics. Patients showing sPIC were compared with patients who did not, using univariate statistics. Multivariate analyses with a split-sample validation procedure were used to assess whether predictive models could be developed using independent data sets. RESULTS: O 295 patients, 74 (25.1%) showed sPIC. All patients showing sPIC needed extra medication, 9% (n = 7) required physically restraints, and 5% (n = 4) had to be secluded. Univariate analyses showed several trends: patients with sPIC were more often males (P = 0.05), had more often history of cerebrovascular incident (P = 0.02), did not use concomitant selective serotonin reuptake inhibitors (P = 0.01), received higher median dosage of succinylcholine (P = 0.02), and received pretreatment with flumazenil more often (P = 0.07), but these associations did not remain significant after correction for multiple comparisons. Multiple logistic regression analysis did not result in a model that could predict sPIC in the holdout data set. CONCLUSIONS: In this retrospective naturalistic study in 295 ECT patients, the prevalence of sPIC appeared to be 25%. Patients showing sPIC were characterized by male sex, history of cerebrovascular incident, use of higher-dose succinylcholine, and pretreatment with flumazenil. However, multivariate analysis revealed no significant model to predict sPIC in independent data.

Seizure duration predicts postictal electroencephalographic recovery after electroconvulsive therapy-induced seizures.

OBJECTIVE: We aim to provide a quantitative description of the relation between seizure duration and the postictal state using features extracted from the postictal electroencephalogram (EEG). METHODS: Thirty patients with major depressive disorder treated with electroconvulsive therapy (ECT) were studied with continuous EEG before, during, and after ECT-induced seizures. EEG recovery was quantified as the spectral difference between postictal and baseline EEG using the temporal brain symmetry index (BSI). The postictal temporal EEG evolution was modeled with a single exponential. The parameters of the model, including the time constant τ, describe the change and speed of postictal EEG recovery. The change from baseline EEG at t = 60 minutes post-seizure (ΔBSI) was calculated from the exponential fit. Postictal clinical reorientation time (ROT) was clinically established. A multivariate generalized multi-level Bayesian model was estimated with seizure duration and ROT as predictors of τ and ΔBSI. RESULTS: EEG features of 290 seizures and postictal states were used for analyses. The model faithfully described the dynamics of the postictal EEG in nearly all patients. Seizure duration was associated with the recovery time constant, τ, and ΔBSI. ROT was associated with τ, but not with ΔBSI. CONCLUSIONS: Longer seizures are associated with slower postictal EEG recovery and more enduring EEG changes compared to baseline. SIGNIFICANCE: Quantitative EEG allows objective assessment of the postictal state.

Negative cognitive schema modification as mediator of symptom improvement after electroconvulsive therapy in major depressive disorder.

BACKGROUND: Electroconvulsive therapy (ECT) is a potent option for treatment-resistant major depressive disorder (MDD). Cognitive models of depression posit that negative cognitions and underlying all-or-nothing negative schemas contribute to and perpetuate depressed mood. This study investigates whether ECT can modify negative schemas, potentially via memory reactivation, and whether such changes are related to MDD symptom improvement. METHOD: Seventy-two patients were randomized to either an emotional memory reactivation electroconvulsive therapy (EMR-ECT) or control memory reactivation electroconvulsive therapy (CMR-ECT) intervention prior to ECT-sessions in a randomized controlled trail. Emotional memories associated with patients' depression were reactivated before ECT-sessions. At baseline and after the ECT-course, negative schemas and depression severity were assessed using the Dysfunctional Attitude Scale (DAS) and Hamilton Depression Rating Scale HDRS. Mediation analyses were used to examine whether the effects of ECT on HDRS-scores were mediated by changes in DAS-scores or vice versa. RESULTS: Post-ECT DAS-scores were significantly lower compared to baseline. Post-ECT, the mean HDRS-score of the whole sample (15.10 ± 8.65 [SD]; n = 59) was lower compared to baseline (24.83 ± 5.91 [SD]). Multiple regression analysis showed no significant influence of memory reactivation on schema improvement. Path analysis showed that depression improvement was mediated by improvement of negative cognitive schemas. CONCLUSION: ECT is associated with improvement of negative schemas, which appears to mediate the improvement of depressive symptoms. An emotional memory intervention aimed to modify negative schemas showed no additional effect.