Structural changes induced by electroconvulsive therapy are associated with clinical outcome.

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment option for major depressive disorder, so understanding whether its clinical effect relates to structural brain changes is vital for current and future antidepressant research. OBJECTIVE: To determine whether clinical response to ECT is related to structural volumetric changes in the brain as measured by structural magnetic resonance imaging (MRI) and, if so, which regions are related to this clinical effect. We also determine whether a similar model can be used to identify regions associated with electrode placement (unilateral versus bilateral ECT). METHODS: Longitudinal MRI and clinical data (Hamilton Depression Rating Scale) was collected from 10 sites as part of the Global ECT-MRI research collaboration (GEMRIC). From 192 subjects, relative changes in 80 (sub)cortical areas were used as potential features for classifying treatment response. We used recursive feature elimination to extract relevant features, which were subsequently used to train a linear classifier. As a validation, the same was done for electrode placement. We report accuracy as well as the structural coefficients of regions included in the discriminative spatial patterns obtained. RESULTS: A pattern of structural changes in cortical midline, striatal and lateral prefrontal areas discriminates responders from non-responders (75% accuracy, p < 0.001) while left-sided mediotemporal changes discriminate unilateral from bilateral electrode placement (81% accuracy, p < 0.001). CONCLUSIONS: The identification of a multivariate discriminative pattern shows that structural change is relevant for clinical response to ECT, but this pattern does not include mediotemporal regions that have been the focus of electroconvulsive therapy research so far.

The electroshock triangle: disputes about the ECT apparatus prototype and its display in the 1960s.

In the early 1960s, a climate of public condemnation of electroconvulsive therapy was emerging in the USA and Europe. In spite of this, the electroshock apparatus prototype, introduced in Rome in 1938, was becoming hotly contended. This article explores the disputes around the display of the electroshock apparatus prototype in the summer of 1964 and sheds new light on the triangle of personalities that shaped its future: Karl and William Menninger, two key figures of American psychiatry in Topeka; their competitor, Adalberto Pazzini, the founder of the Sapienza Museum of the History of Medicine in Rome; and, between them, Lucio Bini, one of the original inventors of ECT, who died unexpectedly that summer.

Intraclass correlations of seizure duration by wavelet transform, sample entropy, and visual determination in electroconvulsive therapy.

Although electroconvulsive therapy seizure duration has been shown to have limited relevance to efficacy, seizure duration remains important for clinically valid stimulus efficiency. There has been no report on seizure duration using sample entropy with Thymatron (Somatics, Inc), which is widely used in Japan. Furthermore, wavelet transform analysis is also suitable for a seizure because of the wide range of dominant frequencies. Therefore, in this study with Thymatron, the intraclass correlations of seizure duration determined by sample entropy, wavelet transform, and visual determination were investigated to determine whether these methods were applicable for clinical use. Wavelet transform, sample entropy, and the human rater had high intraclass correlations for seizure duration. The present results indicate that wavelet transform and sample entropy can be useful in the clinical electroconvulsive therapy setting, and they may also be suitable for clinical research into the mechanisms of the generalized tonic-clonic seizures related to the efficacy of electroconvulsive therapy.

Transcranial electrical stimulation nomenclature.

Transcranial electrical stimulation (tES) aims to alter brain function non-invasively by applying current to electrodes on the scalp. Decades of research and technological advancement are associated with a growing diversity of tES methods and the associated nomenclature for describing these methods. Whether intended to produce a specific response so the brain can be studied or lead to a more enduring change in behavior (e.g. for treatment), the motivations for using tES have themselves influenced the evolution of nomenclature, leading to some scientific, clinical, and public confusion. This ambiguity arises from (i) the infinite parameter space available in designing tES methods of application and (ii) varied naming conventions based upon the intended effects and/or methods of application. Here, we compile a cohesive nomenclature for contemporary tES technologies that respects existing and historical norms, while incorporating insight and classifications based on state-of-the-art findings. We consolidate and clarify existing terminology conventions, but do not aim to create new nomenclature. The presented nomenclature aims to balance adopting broad definitions that encourage flexibility and innovation in research approaches, against classification specificity that minimizes ambiguity about protocols but can hinder progress. Constructive research around tES classification, such as transcranial direct current stimulation (tDCS), should allow some variations in protocol but also distinguish from approaches that bear so little resemblance that their safety and efficacy should not be compared directly. The proposed framework includes terms in contemporary use across peer-reviewed publications, including relatively new nomenclature introduced in the past decade, such as transcranial alternating current stimulation (tACS) and transcranial pulsed current stimulation (tPCS), as well as terms with long historical use such as electroconvulsive therapy (ECT). We also define commonly used terms-of-the-trade including electrode, lead, anode, and cathode, whose prior use, in varied contexts, can also be a source of confusion. This comprehensive clarification of nomenclature and associated preliminary proposals for standardized terminology can support the development of consensus on efficacy, safety, and regulatory standards.

Computational comparison of conventional and novel electroconvulsive therapy electrode placements for the treatment of depression.

BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective treatment for severe psychiatric disorders. Despite its high efficacy, the use of ECT would be greater if the risk of cognitive side effects were reduced. Over the last 20 years, developments in ECT technique, including improvements in the dosing methodology and modification of the stimulus waveform, have allowed for improved treatment methods with reduced adverse cognitive effects. There is increasing evidence that the electrode placement is important for orienting the electrical stimulus and therefore modifying treatment outcomes, with potential for further improvement of the placements currently used in ECT. OBJECTIVE: We used computational modelling to perform an in-depth examination into regional differences in brain excitation by the ECT stimulus for several lesser known and novel electrode placements, in order to investigate the potential for an electrode placement that may optimise clinical outcomes. METHODS: High resolution finite element human head models were generated from MRI scans of three subjects. The models were used to compare regional differences in average electric field (EF) magnitude among a total of thirteen bipolar ECT electrode placements, i.e. three conventional placements as well as ten lesser known and novel placements. RESULTS AND CONCLUSION: In this exploratory study on a systemic comparison of thirteen ECT electrode placements, the EF magnitude at regions of interest (ROIs) was highly dependent upon the position of both electrodes, especially the ROIs close to the cortical surface. Compared to conventional right-unilateral (RUL) ECT using a temporo-parietal placement, fronto-parietal and supraorbito-parietal RUL also robustly stimulated brain regions considered important for efficacy, while sparing regions related to cognitive functions, and may be a preferrable approach to the currently used placement for RUL ECT. The simulations also found that regional average EF magnitude varied between individual subjects, due to factors such as head size, and results also depended on the size of the defined ROI.

Medical Device Classification Procedures: Incorporating Food and Drug Administration Safety and Innovation Act Procedures. Final rule.

The Food and Drug Administration (FDA, the Agency, or we) is issuing a final rule to amend its regulations governing classification and reclassification of medical devices to conform to the applicable provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act) as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA). FDA is also making additional changes unrelated to the FDASIA requirements, to update its regulations governing the classification and reclassification of medical devices. FDA is taking this action to codify the procedures and criteria that apply to the classification and reclassification of medical devices and to provide for classification of devices in the lowest regulatory class consistent with the public health and the statutory scheme for device regulation.

Neurostimulation for depression in epilepsy.

Epilepsy is often associated with comorbid psychiatric illnesses that can significantly impact its long-term course. The most frequent of these psychiatric comorbidities is major depressive disorder, which affects an estimated 40% of patients with epilepsy. Many patients are underdiagnosed or undertreated, yet managing their mood symptoms is critical to improving their outcomes. When conventional psychiatric treatments fail in the management of depression, neuromodulation techniques may offer promise, including electroconvulsive therapy (ECT), vagus nerve stimulation (VNS), and repetitive transcranial magnetic stimulation (rTMS), as discussed in this review. "This article is part of the Supplement issue Neurostimulation for Epilepsy."

A novel Seizure Quality Index based on ictal parameters for optimizing clinical decision making in electroconvulsive therapy. Part 1: development.

Early identification of patients at high risk for an unfavorable outcome to ECT during the course might be beneficial because it provides an opportunity for timely intensification or optimization of stimulus conditions. We aimed to develop a new Seizure Quality Index (SQI) that delivers a clinical relevant outcome prediction early in the treatment course and can be used within common clinical setting. An observational study was conducted. Patients (n = 86) with a depressive episode and the clinical decision for ECT (right unilateral, brief pulse) were included, and several ictal parameters derived from the second ECT session and the clinical outcome of the patients were documented. Optimal cut-off points for five different domains of ictal adequacy for younger and older patients for the prediction of "non-response" and "non-remission" based on seizure quality was determined by the Youden Index and a sum score was built. Logistic regression analyses tested the predictive power of derived models. For both outcome variables "non-response" and "non-remission", the logistic regression models were statistically significant, albeit for remission only for subjects below the age of 65 years (χ2 = 17.9, p = 0.001) and (χ2 = 6.4, p = 0.020), respectively. The models correctly classified 87.2% (non-response) and 50.0% (non-remission) of the cases. ROC curve analysis showed an AUC of 0.87 (non-response) and 0.70 (non-remission). In elderly patients (> 65), no such model could be established due to a response rate of 100%. Our data provide promising, clinically relevant results about the prediction of response to ECT at an early stage for patients with depression.

Electroconvulsive therapy for depression in a patient with an Inspire hypoglossal nerve stimulator device for obstructive sleep apnea: A case report.

OUTCOME OBJECTIVES: METHODS: This is a case report of a patient who underwent placement and initiation of a hypoglossal nerve stimulator device in the context of receiving electroconvulsive therapy for bipolar depression between February and September 2016. To our knowledge, this has not yet been reported in the literature. Outcome measurements included successful device activation and successful device use throughout electroconvulsive therapy. RESULTS: The patient underwent successful device implantation, activation, and use without disruption throughout electroconvulsive therapy sessions. No special device deactivation was required during electroconvulsive therapy sessions. CONCLUSION: Obstructive sleep apnea is a common disorder that causes significant reduction in quality of life and is an independent risk factor for multiple comorbidities. Electroconvulsive therapy is an established treatment for medication-refractory depression with minimal risk in most patient populations. This is the first report in the literature of a patient undergoing ECT for bipolar depression with recent activation of Inspire hypoglossal nerve stimulator who had no disruption in the function of his implanted device.

Neurological Devices; Reclassification of Electroconvulsive Therapy Devices; Effective Date of Requirement for Premarket Approval for Electroconvulsive Therapy Devices for Certain Specified Intended Uses. Final order.

The Food and Drug Administration (FDA) is issuing a final order to reclassify the electroconvulsive therapy (ECT) device for use in treating catatonia or a severe major depressive episode (MDE) associated with major depressive disorder (MDD) or bipolar disorder (BPD) in patients age 13 years and older who are treatment-resistant or who require a rapid response due to the severity of their psychiatric or medical condition, which is a preamendments class III device, into class II (special controls). FDA is also issuing this final order to require the filing of a premarket approval application (PMA) or a notice of completion of a product development protocol (PDP) for the preamendments class III ECT devices for all other uses that are not being reclassified to class II (product code GXC).

Base de datos clínica de terapia electroconvulsiva: influencia de edad y género en la carga eléctrica / Electroconvulsive therapy clinical database: Influence of age and gender on the electrical charge

Introducción. A partir de una base de datos clínica de terapia electroconvulsiva (TEC) se pretende corroborar la influencia de la edad y el género en la carga eléctrica administrada en una población determinada. Material y método. Estudio observacional, prospectivo y longitudinal, con análisis descriptivo, de una base de datos que incluye el total de sesiones de TEC bilaterales frontotemporales realizadas con la Mecta spECTrum 5000Q(R) entre 2006 y 2012. Es una muestra de 4.337 sesiones de TEC realizadas a 187 pacientes. Mediante regresión lineal de efectos mixtos se realiza un análisis ponderado por el inverso del número de sesiones de TEC realizadas por cada paciente y por año de tratamiento. Resultados. Los resultados indican que la edad está relacionada con cambios en la carga requerida (p=0,031): a mayor edad, mayor aumento de carga. El género también se relaciona con cambios en la carga (p=0,014): las mujeres requerirían 87,3mC menos de media que los hombres. Incluyendo los efectos de edad y género en el mismo modelo, ambos resultan significativos (p=0,0080 y p=0,0041), de modo que a igualdad de edad, las mujeres requieren 99,0mC menos de carga que los hombres, y en ambos géneros aumenta la carga 2,3mC por año de edad. Conclusiones. Del análisis se obtiene que el efecto de la edad en la dosificación de la carga eléctrica es todavía más significativo cuando se tiene en cuenta el género. Es de interés promover la recogida sistemática de datos para un mejor conocimiento y aplicación de la técnica (AU)

Introduction. The influence of age and gender in the electrical charge delivered in a given population was analysed using an electroconvulsive therapy (ECT) clinical database. Material and method. An observational, prospective, longitudinal study with descriptive analysis was performed using data from a database that included total bilateral frontotemporal ECT carried out with a Mecta spECTrum 5000Q(R) in our hospital over 6 years. From 2006 to 2012, a total of 4,337 ECT were performed on 187 patients. Linear regression using mixed effects analysis was weighted by the inverse of the number of ECT performed on each patient per year of treatment. Results. The results indicate that age is related with changes in the required charge (P=.031), as such that the older the age a higher charge is needed. Gender is also associated with changes in charge (P=.014), with women requiring less charge than men, a mean of 87.3mC less. When the effects of age and gender are included in the same model, both are significant (P=.0080 and P=.0041). Thus, for the same age, women require 99.0mC less charge than men, and in both genders the charge increases by 2.3mC per year. Conclusions. From our study, it is concluded that the effect of age on the dosage of the electrical charge is even more significant when related to gender. It would be of interest to promote the systematic collection of data for a better understanding and application of the technique (AU)

Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins.

Electroconvulsive seizure (ECS) is an experimental animal model of electroconvulsive therapy, the most effective treatment for severe depression. ECS induces generalized tonic-clonic seizures with low mortality and neuronal death and is a widely-used model to screen anti-epileptic drugs. Here, we describe an ECS induction method in which a brief 55-mA current is delivered for 0.5 s to male rats 200 - 250 g in weight via ear-clip electrodes. Such bilateral stimulation produced stage 4 - 5 clonic seizures that lasted about 10 s. After the cessation of acute or chronic ECS, most rats recovered to be behaviorally indistinguishable from sham "no seizure" rats. Because ECS globally elevates brain activity, it has also been used to examine activity-dependent alterations of synaptic proteins and their effects on synaptic strength using multiple methods. In particular, subcellular fractionation of the postsynaptic density (PSD) in combination with Western blotting allows for the quantitative determination of the abundance of synaptic proteins at this specialized synaptic structure. In contrast to a previous fractionation method that requires large amount of rodent brains, we describe here a small-scale fractionation method to isolate the PSD from the hippocampi of a single rat, without sucrose gradient centrifugation. Using this method, we show that the isolated PSD fraction contains postsynaptic membrane proteins, including PSD95, GluN2B, and GluA2. Presynaptic marker synaptophysin and soluble cytoplasmic protein α-tubulin were excluded from the PSD fraction, demonstrating successful PSD isolation. Furthermore, chronic ECS decreased GluN2B expression in the PSD, indicating that our small-scale PSD fractionation method can be applied to detect the changes in hippocampal PSD proteins from a single rat after genetic, pharmacological, or mechanical treatments.

Inducción de hipocapnia e hiperoxia con maniobras de hiperventilación reglada en la terapia electroconvulsiva / Hypocapnia and hyperoxia induction using a hyperventilation protocol in electroconvulsive therapy

Introducción. La hiperventilación en las sesiones de terapia electroconvulsiva se ha relacionado con el umbral convulsivo, las características de la convulsión y los efectos cognitivos. No existe consenso sobre el procedimiento óptimo de aplicación de las maniobras de hiperventilación durante la terapia electroconvulsiva. Material y métodos. Evaluación prospectiva de los efectos del uso sistematizado de maniobras de hiperventilación con mascarilla facial y capnografía (hiperventilación reglada [HVr]) en los parámetros ventilatorios y de la convulsión. Muestra de 130 sesiones (65 realizadas con hiperventilación según la práctica habitual y 65 sucesivas con HVr) de 35 pacientes en un periodo de 10 semanas. Resultados. Las maniobras de HVr disminuyeron el CO2 espirado e incrementaron la saturación de O2 significativamente (p<0,001). La disminución media de CO2 alcanzada fue de 6,52±4,75mmHg (IC 95% −7,7 a −5,3). Los valores de CO2 tras la HVr correlacionaron significativamente con la duración de la convulsión, y los de O2, con otros índices electroencefalográficos de calidad. En las sesiones con HVr, en comparación con las sesiones realizadas con hiperventilación según la práctica habitual, el alargamiento medio de la convulsión motora y electroencefalográfica fue de 3,86±14,62 y de 4,73±13,95s, respectivamente, sin diferencias en los demás parámetros ictales. Conclusiones. Las maniobras de HVr propuestas modifican de forma relevante los parámetros ventilatorios. La hipocapnia y la hiperoxia obtenidas al aplicar estas maniobras alargan la duración de las convulsiones sin empeorar la calidad del trazado electroencefalográfico. El uso de protocolos de HVr es generalizable y puede mejorar el procedimiento de la terapia electroconvulsiva sin añadir costes (AU)

Introduction. Hyperventilation in electroconvulsive therapy sessions has been associated with seizure threshold, seizure characteristics, and cognitive effects. There is no consensus on the optimal procedure of applying hyperventilation manoeuvres during electroconvulsive therapy. Material and methods. Prospective evaluation of the effects of systematic use of hyperventilation manoeuvres with facial mask and capnography (protocolized hyperventilation [pHV]), on ventilation parameters and on seizures. The study included a sample of 130 sessions (65 performed according to hyperventilation standard practice and 65 successive sessions, with pHV) of 35 patients over a period of 10 weeks. Results. The pHV manoeuvres reduced exhaled CO2 and increased O2 saturation significantly (P<.001). The average CO2 reduction achieved was 6.52±4.75mmHg (95% CI −7.7 to −5.3). The CO2 values after pHV correlated significantly with seizure duration and O2 values, with other electroencephalographic quality indices. In pHV sessions, compared with sessions performed according to hyperventilation standard practice, the average lengthening of the motor and electroencephalographic seizure was 3.86±14.62 and 4.73±13.95s, respectively. No differences were identified in other ictal quality parameters. Conclusions. The proposed pHV manoeuvres significantly modify ventilation parameters. The hypocapnia and hyperoxia obtained by applying these manoeuvres lengthen the duration of seizures without worsening the quality of the electroencephalographic trace. The use of pHV is generalisable and might improve electroconvulsive therapy procedure without adding costs (AU)

Electroconvulsive therapy clinical database: Influence of age and gender on the electrical charge. / Base de datos clínica de terapia electroconvulsiva: influencia de edad y género en la carga eléctrica.

INTRODUCTION: The influence of age and gender in the electrical charge delivered in a given population was analysed using an electroconvulsive therapy (ECT) clinical database. MATERIAL AND METHOD: An observational, prospective, longitudinal study with descriptive analysis was performed using data from a database that included total bilateral frontotemporal ECT carried out with a Mecta spECTrum 5000Q® in our hospital over 6 years. From 2006 to 2012, a total of 4,337 ECT were performed on 187 patients. Linear regression using mixed effects analysis was weighted by the inverse of the number of ECT performed on each patient per year of treatment. RESULTS: The results indicate that age is related with changes in the required charge (P=.031), as such that the older the age a higher charge is needed. Gender is also associated with changes in charge (P=.014), with women requiring less charge than men, a mean of 87.3mC less. When the effects of age and gender are included in the same model, both are significant (P=.0080 and P=.0041). Thus, for the same age, women require 99.0mC less charge than men, and in both genders the charge increases by 2.3mC per year. CONCLUSIONS: From our study, it is concluded that the effect of age on the dosage of the electrical charge is even more significant when related to gender. It would be of interest to promote the systematic collection of data for a better understanding and application of the technique.