Resting-state electroencephalographic functional network alterations in major depressive disorder following magnetic seizure therapy.

Magnetic seizure therapy (MST) is emerging as a safe and well-tolerated experimental intervention for major depressive disorder (MDD), with very minimal cognitive side-effects. However, the underlying mechanism of action of MST remains uncertain. Here, we used resting-state electroencephalography (RS-EEG) to characterise the physiological effects of MST for treatment resistant MDD. We recorded RS-EEG in 21 patients before and after an open label trial of MST applied over the prefrontal cortex using a bilateral twin coil. RS-EEG was analysed for changes in functional connectivity, network topology, and spectral power. We also ran further baseline comparisons between the MDD patients and a cohort of healthy controls (n = 22). Network-based connectivity analysis revealed a functional subnetwork of significantly increased theta connectivity spanning frontal and parieto-occipital channels following MST. The change in theta connectivity was further found to predict clinical response to treatment. An additional widespread subnetwork of reduced beta connectivity was also elucidated. Graph-based topological analyses showed an increase in functional network segregation and reduction in integration in the theta band, with a decline in segregation in the beta band. Finally, delta and theta power were significantly elevated following treatment, while gamma power declined. No baseline differences between MDD patients and healthy subjects were observed. These results highlight widespread changes in resting-state brain dynamics following a course of MST in MDD patients, with changes in theta connectivity providing a potential physiological marker of treatment response. Future prospective studies are required to confirm these initial findings.

Study protocol for a parallel-group, double-blinded, randomized, controlled, noninferiority trial: the effect and safety of hybrid electroconvulsive therapy (Hybrid-ECT) compared with routine electroconvulsive therapy in patients with depression.

BACKGROUND: Electroconvulsive therapy (ECT) is the most rapid and effective treatment for patients with depression, ECT can achieve remarkable antidepressant effects in the initial 3-4 sessions, but significant side effects limit its use. However, recent low-charge electrotherapy (LCE) studies have demonstrated antidepressant or antipsychotic effects with significantly fewer side effects. The aim of this study is to propose a novel two-step charge set strategy for ECT treatment, referred to as Hybrid-ECT, to decrease side effects by using a low charge while preserving treatment efficacy. METHODS/DESIGN: A randomized, double-blinded, standard-controlled, parallel-group design will be carried out. We plan to enroll 112 inpatients diagnosed with depression (unipolar or bipolar) and randomly assign them to conventional ECT (control group) or to Hybrid-ECT (treatment group, 3 ECT sessions followed by LCE sessions (approximately 2.8 joules per session)). We will evaluate participants across a wide variety of domains including clinical symptoms, cognitive, psychological and functional metrics. We will also perform magnetic resonance imaging (MRI) and event-related potential (ERPs) assessments during treatment to explore brain function differences between ECT and LCE. DISCUSSION: This research proposes a simple but completely novel ECT strategy that aims to rapidly relieve depressive symptoms and minimize side effects. The mechanism of ECT and LCE will be further discussed. TRIAL REGISTRATION: Chinese Clinical Trial Registry, Number: ChiCTR1900022905 (Registration date: April 30, 2019).

Reduced risk of stroke among psychiatric patients receiving ECT: A population-based cohort study in Taiwan.

Electroconvulsive therapy (ECT) as well as the diseases it treats have been associated with stroke and cognitive impairment. We investigate the relationship between ECT and the subsequent development of stroke in patients with different severe mental illnesses. Tapping Taiwan's National Health Insurance Research Database, we identified patients diagnosed with severe mental illnesses who had received ECT between Jan 1, 2002 and Dec 31, 2007. A comparison cohort was constructed of patients who were matched by age, gender, and diagnosis but did not receive ECT. The patients were then followed up for occurrence of subsequent new-onset stroke. We identified 6264 patients had been diagnosed with mental illness and had received ECT. They were matched with 18,664 mentally ill patients who had not. The study cohort had a lower incidence of subsequent stroke than the matched controls, after controlling for age, diabetes, hypertension, coronary heart disease and enrollee sociodemographic category, risk factors for stroke in both study and control cohorts. ECT is associated with reduced risk of subsequent stroke in patients with severe mental illnesses in Taiwan. Therefore, clinicians should not let risk of stroke stop them from suggesting ECT to physically healthy patients who might benefit from this therapy.

The Future of Brain Stimulation Treatments.

Trends in brain stimulation include becoming less invasive, more focal, and more durable with less toxicity. Several of the more interesting new potentially disruptive technologies that are just making their way through basic and sometimes clinical research studies include low-intensity focused ultrasound and temporally interfering electric fields. It is possible, and even likely, that noninvasive brain stimulation may become the dominant form of brain treatments over the next 20 years. The future of brain stimulation therapeutics is bright.

Extreme variability in succinylcholine dose for muscle relaxation in electroconvulsive therapy.

OBJECTIVES: To determine what dose of succinylcholine falls outside the range of 2 SD above or below the mean optimal dose of 0.9 mg/kg used for electroconvulsive therapy (ECT). METHODS: In this retrospective chart review, for all patients who received ECT at our institution within the 5-year study period, the initial dose of succinylcholine in milligrams per kilogram was compared with subsequent doses after adjustments were made for individual patient responses. Mean and SD were calculated using the dose of succinylcholine, once the optimal dose for each patient had been determined, based on clinical response. RESULTS: Five hundred patients treated during the 5-year period met inclusion criteria, 180 (36%) of whom required an adjustment of the succinylcholine dosing either above (119 patients) or below (61 patients) the 0.9 mg/kg standard after their first treatment. CONCLUSIONS: In those patients who required an adjustment of 2 SD either above or below the mean dose of succinylcholine (29 patients, 5.8%), adequate neuromuscular blockade was only achieved with either an increased dose of up to 2.10 mg/kg or a decreased dose as low as 0.29 mg/kg.

Neurostimulation techniques in the treatment of cocaine dependence: A review of the literature.

OBJECTIVE: Cocaine use disorder is a very common condition that represents a substantial public health problem, and no effective pharmacological or psychological therapies have been identified to date. Urgent therapeutic alternatives are therefore needed such as neurostimulation techniques. The purpose of this review is to describe and discuss studies that have evaluated the safety and efficacy of these techniques for the treatment of cocaine dependence. METHODS: The electronic literature on repetitive transcranial magnetic stimulation, theta-burst stimulation, deep transcranial magnetic stimulation, transcranial direct current stimulation, magnetic seizure therapy, electroconvulsive therapy, cranial electro-stimulation, and deep brain stimulation in the treatment of cocaine addiction were reviewed. RESULTS: Most of these studies which are few in numbers and with limited sample sizes found that some of these neurostimulation techniques, particularly transcranial magnetic stimulation, and transcranial direct current stimulation are safe and potentially effective in the reduction of craving to cocaine. Although deep brain stimulation showed some good results in one patient, no conclusion can be drawn so far concerning the efficacy and safety of this approach. CONCLUSION: Given the somewhat promising results of some of the studies, future controlled studies with larger samples, and optimal stimulus parameters should be designed to confirm the short- and long-term safety and efficacy of neurostimulation techniques to treat cocaine addiction.

Guía de práctica clínica sobre la depresión mayor en la infancia y adolescencia: actualización / Clinical practice guide on major depression in childhood and adolescence: update

Objetivos: Mejorar la atención sanitaria prestada a los niños y adolescentes con depresión en el ámbito de la atención primaria y especializada. Ofrecer recomendaciones al profesional sanitario para la atención de estos pacientes. Desarrollar indicadores de evaluación de la calidad asistencial. Ayudar a los pacientes y a sus familiares a la toma de decisiones informada y a la mejora de la comunicación entre los pacientes y los profesionales. No se abordan otros servicios, como los sociales, educacionales o de tiempo libre. Aspectos contemplados Las áreas clínicas que contempla la guía son: - Criterios diagnósticos y caracterización de la depresión infanto-juvenil. - Factores de riesgo y de protección. - Evaluación. - Perspectivas de pacientes y familiares. - Cribado en atención primaria. - Opciones de tratamiento de la depresión: - Tratamiento psicológico (modalidades, numero de sesiones, duración). - Manejo farmacológico (indicación, dosis, duración, cese, efectos secundarios, toxicidad y ausencia de respuesta a la medicación). - Tratamiento combinado. - Prevención de recaídas/recurrencia. - Estrategias para la depresión que no responde al tratamiento. - Tratamiento de la depresión mayor con síntomas psicóticos. - Otras alternativas terapéuticas: ejercicio físico, intervenciones online y terapias alternativas. - El consentimiento informado desde el punto de vista legal en España. - Algoritmo terapéutico: criterios de derivación y manejo según gravedad. Aspectos no abordados en la GPC 1) Los trastornos distímico, bipolar, ni el adaptativo. 2) La prevención primaria de la depresión en la infancia y adolescencia. 3) La prevención de la conducta suicida, debido a que este aspecto se recoge en la GPC de Prevención y Tratamiento de la Conducta Suicida del Programa de GPC en el SNS, en su apartado especifico sobre infancia y adolescencia.

Neuroprotective Effect of Modified Electroconvulsive Therapy for Schizophrenia: A Proton Magnetic Resonance Spectroscopy Study.

The underlying mechanism of modified electroconvulsive therapy (MECT) treatment for drug-resistant and catatonic schizophrenia remains unclear. Here, we aim to investigate whether MECT exerts its antipsychotic effects through elevating N-acetylaspartate (NAA) concentration measured by proton magnetic resonance spectroscopy (H-MRS). Multiple-voxel H-MRS was acquired in the bilateral prefrontal cortex (PFC) and thalamus to obtain measures of neurochemistry in 32 MECT, 34 atypical antipsychotic-treated schizophrenic patients, and 34 healthy controls. We found that both MECT and atypical antipsychotic treatments showed significant antipsychotic efficacy. MECT and atypical antipsychotic treatments reversed the reduced NAA/creatine ratio (NAA/Cr) in the left PFC and left thalamus in schizophrenic patients compared with healthy controls. Furthermore, the NAA/Cr ratio after treatments was significant higher in the MECT group, but not in the medication group. Our findings demonstrate that eight times of MECT elevated the relative NAA concentration to display neuroprotective effect, which may be the underlying mechanism of rapid antipsychotic efficacy.

Minimum Electric Field Exposure for Seizure Induction with Electroconvulsive Therapy and Magnetic Seizure Therapy.

Lowering and individualizing the current amplitude in electroconvulsive therapy (ECT) has been proposed as a means to produce stimulation closer to the neural activation threshold and more focal seizure induction, which could potentially reduce cognitive side effects. However, the effect of current amplitude on the electric field (E-field) in the brain has not been previously linked to the current amplitude threshold for seizure induction. We coupled MRI-based E-field models with amplitude titrations of motor threshold (MT) and seizure threshold (ST) in four nonhuman primates (NHPs) to determine the strength, distribution, and focality of stimulation in the brain for four ECT electrode configurations (bilateral, bifrontal, right-unilateral, and frontomedial) and magnetic seizure therapy (MST) with cap coil on vertex. At the amplitude-titrated ST, the stimulated brain subvolume (23-63%) was significantly less than for conventional ECT with high, fixed current (94-99%). The focality of amplitude-titrated right-unilateral ECT (25%) was comparable to cap coil MST (23%), demonstrating that ECT with a low current amplitude and focal electrode placement can induce seizures with E-field as focal as MST, although these electrode and coil configurations affect differently specific brain regions. Individualizing the current amplitude reduced interindividual variation in the stimulation focality by 40-53% for ECT and 26% for MST, supporting amplitude individualization as a means of dosing especially for ECT. There was an overall significant correlation between the measured amplitude-titrated ST and the prediction of the E-field models, supporting a potential role of these models in dosing of ECT and MST. These findings may guide the development of seizure therapy dosing paradigms with improved risk/benefit ratio.

Electroconvulsive Therapy Considerations for Transgendered Patients.

As the transgender patient population continues to grow, health care providers will need to become aware of elements unique to the transgender community in order to provide the highest quality of care. Neuromuscular blockade with succinylcholine is routinely administered to patients undergoing electroconvulsive therapy (ECT). Decreased amounts or activity of pseudocholinesterase in serum can lead to prolonged duration of muscle paralysis. Causes of reduced action by pseudocholinesterase include genetically abnormal enzymes, reduced hepatic production, pregnancy, and various drug interactions. Estrogen supplementation taken by transitioning patients may affect the duration of neuromuscular blockade.This is a case of a 32-year-old male-to-female transgender patient with prolonged apnea following ECT treatment for severe, refractory depression. Further investigation revealed the patient was on estrogen therapy as a part of her transition and laboratory testing demonstrated reduced serum pseudocholinesterase activity. Further laboratory testing demonstrated reduced serum pseudocholinesterase activity. Succinylcholine dosing was titrated to an appropriate level to avoid prolonged apnea in subsequent ECT treatments. Physicians and other health care providers are faced with a unique population in the transgender community and must be aware of distinctive circumstances when providing care to this group. Of specific interest, many transitioning and transitioned patients can be on chronic estrogen supplementation. Neuromuscular blockade in those patients require attention from the anesthesiology care team as estrogen compounds may decrease pseudocholinesterase levels and lead to prolonged muscle paralysis from succinylcholine.

Variations in myo-inositol in fronto-limbic regions and clinical response to electroconvulsive therapy in major depression.

Though electroconvulsive therapy (ECT) is an established treatment for severe depression, the neurobiological factors accounting for the clinical effects of ECT are largely unknown. Myo-inositol, a neurometabolite linked with glial activity, is reported as reduced in fronto-limbic regions in patients with depression. Whether changes in myo-inositol relate to the antidepressant effects of ECT is unknown. Using magnetic resonance spectroscopy ((1)H-MRS), we measured dorsomedial anterior cingulate cortex (dmACC) and left and right hippocampal myo-inositol in 50 ECT patients (mean age: 43.78, 14 SD) and 33 controls (mean age: 39.33, 12 SD) to determine cross sectional effects of diagnosis and longitudinal effects of ECT. Patients were scanned prior to treatment, after the second ECT and at completion of the ECT index series. Controls were scanned twice at intervals corresponding to patients' baseline and end of treatment scans. Myo-inositol increased over the course of ECT in the dmACC (p = 0.042). A significant hemisphere by clinical response effect was observed for the hippocampus (p = 0.003) where decreased myo-inositol related to symptom improvement in the left hippocampus. Cross-sectional differences between patients and controls at baseline were not detected. Changes in myo-inositol observed in the dmACC in association with ECT and in the hippocampus in association with ECT-related clinical response suggest the mechanisms of ECT could include gliogenesis or a reversal of gliosis that differentially affect dorsal and ventral limbic regions. Change in dmACC myo-inositol diverged from control values with ECT suggesting compensation, while hippocampal change suggested normalization.

An Investigation of Patient Preferences for Music Played Before Electroconvulsive Therapy.

OBJECTIVE: Patients often feel anxious before electroconvulsive therapy (ECT), which can lead to avoidance of treatments. Music is a noninvasive safe option to reduce anxiety in the preoperative setting. Therefore, we examined patients' preferences of listening to music while receiving ECT by providing music-by way of headphones or speakers-to participants before treatment. METHODS: Patients receiving ECT were recruited for this study. Patients served as their own controls in 3 separate music intervention sessions: 1) randomization to music via headphones or speakers, 2) no music, 3) the remaining music intervention. Patients completed a questionnaire related to satisfaction and preferences of music being played before ECT. Patients received a final questionnaire at the end of the study asking which intervention they preferred. RESULTS: Thirty patients completed the study. Ninety percent enjoyed listening to music through speakers. Eighty percent liked listening to music through headphones. Seventeen percent preferred not having any music. The difference in preference between speakers and headphones was not significant (P = 0.563; McNemar-Bowker test). There was no association between preference at the end of the study and the initial assignment of speakers or headphones (P = 0.542 and P = 0.752, respectively; Pearson χ tests). No adverse events were reported. CONCLUSIONS: Music is a low-cost intervention with virtually no side effects that could be offered as an adjunctive therapy for patients receiving ECT. A significant proportion of patients liked hearing music before treatment.

Therapeutic Efficacy of Neurostimulation for Depression: Techniques, Current Modalities, and Future Challenges.

Depression is the most prevalent debilitating mental illness; it is characterized as a disorder of mood, cognitive function, and neurovegetative function. About one in ten individuals experience depression at some stage of their lives. Antidepressant drugs are used to reduce the symptoms but relapse occurs in ~20% of patients. However, alternate therapies like brain stimulation techniques have shown promising results in this regard. This review covers the brain stimulation techniques electroconvulsive therapy, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, vagus nerve stimulation, and deep brain stimulation, which are used as alternatives to antidepressant drugs, and elucidates their research and clinical outcomes.

Bio-heat transfer model of electroconvulsive therapy: Effect of biological properties on induced temperature variation.

A realistic human head model consisting of six tissue layers was modelled to investigate the behavior of temperature profile and magnitude when applying electroconvulsive therapy stimulation and different biological properties. The thermo-electrical model was constructed with the use of bio-heat transfer equation and Laplace equation. Three different electrode montages were analyzed as well as the influence of blood perfusion, metabolic heat and electric and thermal conductivity in the scalp. Also, the effect of including the fat layer was investigated. The results showed that temperature increase is inversely proportional to electrical and thermal conductivity increase. Furthermore, the inclusion of blood perfusion slightly drops the peak temperature. Finally, the inclusion of fat is highly recommended in order to acquire more realistic results from the thermo-electrical models.