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Magnetic seizure therapy in an adolescent with refractory bipolar depression: a case report.

ABSTRACT: Magnetic seizure therapy (MST) has shown efficacy in adult patients with treatment-resistant depression with limited impairment in memory. To date, the use of MST in adolescent depression has not been reported. Here we describe the first successful use of MST in the treatment of an adolescent patient with refractory bipolar depression. This patient received MST in an ongoing open-label study for treatment-resistant major depression. Treatments employed a twin-coil MST apparatus, with the center of each coil placed over the frontal cortex (ie, each coil centered over F3 and F4). MST was applied at 100 Hz and 100% machine output at progressively increasing train durations. Depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale and cognitive function was assessed with a comprehensive neuropsychological battery. This adolescent patient achieved full remission of clinical symptoms after an acute course of 18 MST treatments and had no apparent cognitive decline, other than some autobiographical memory impairment that may or may not be related to the MST treatment. This case report suggests that MST may be a safe and well tolerated intervention for adolescents with treatment-resistant bipolar depression. Pilot studies to further evaluate the effectiveness and safety of MST in adolescents warrant consideration.

SUBMITTER: Noda Y

PROVIDER: S-EPMC4222618 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Magnetic seizure therapy in an adolescent with refractory bipolar depression: a case report.

Noda Yoshihiro Y Daskalakis Zafiris J ZJ Downar Jonathan J Croarkin Paul E PE Fitzgerald Paul B PB Blumberger Daniel M DM

Neuropsychiatric disease and treatment 20141031

Magnetic seizure therapy (MST) has shown efficacy in adult patients with treatment-resistant depression with limited impairment in memory. To date, the use of MST in adolescent depression has not been reported. Here we describe the first successful use of MST in the treatment of an adolescent patient with refractory bipolar depression. This patient received MST in an ongoing open-label study for treatment-resistant major depression. Treatments employed a twin-coil MST apparatus, with the center ...[more]

PMID: 25382978

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Project description:ObjectiveDeep transcranial magnetic stimulation (TMS) with an H-1 coil was recently approved by the U.S. Food and Drug Administration (U.S. FDA) for treatment-resistant depression (TRD) in adults. Studies assessing the safety and effectiveness of deep TMS in adolescent TRD are lacking. The purpose of this brief report is to provide a case history of an adolescent enrolled in an investigational deep TMS protocol.MethodsA case history is described of the first participant of a sham-controlled clinical trial who had a seizure in the course of deep TMS with parameter settings extrapolated from the adult studies that led to US FDA approval (H-1 coil, 120% target stimulation intensity, 18 Hz, 55 trains of 2-second duration, total 1980 pulses).ResultsThe participant was a 17-year-old unmedicated female, with no significant medical history and no history of seizures or of drug or alcohol use. Brain magnetic resonance imaging showed no structural abnormalities. She initially received sham, which was well tolerated. During active treatment sessions, titration began at 85% of motor threshold (MT) and increased by 5% per day. Her weekly MT measurements were stable. On her first day of 120% MT (8th active treatment), during the 48th train, the participant had a generalized, tonic-clonic seizure that lasted 90 seconds and resolved spontaneously. She had an emergency medicine evaluation and was discharged home without anticonvulsant medications. There were no further seizures reported at a 6-month follow-up.ConclusionsWe report a deep TMS-induced generalized tonic-clonic seizure in an adolescent with TRD participating in a clinical trial. Given the demonstrated benefits of deep TMS for adult TRD, research investigating its use in adolescents with TRD is an important area. However, in light of this experience, additional precautions for adolescents should be considered. We propose that further dose-finding investigations are needed to refine adolescent-specific parameters that may be safe and effective for treating adolescents with TRD with deep TMS.

Project description:Importance:There is an unmet need for effective treatments for suicidality in mental disorders. Magnetic seizure therapy (MST) has been investigated as an alternative to electroconvulsive therapy, a known effective treatment for suicidality, in the management of treatment-resistant major depressive disorder, with promising findings. Yet, there are very limited data on the association of MST with suicidality directly. It is important to explore the potential of MST as a viable treatment alternative to electroconvulsive therapy for suicidality. Objective:To determine the association of MST with suicidality in patients with treatment-resistant major depressive disorder. Design, Setting, and Participants:This nonrandomized controlled trial took place at a single tertiary care psychiatric facility in Canada. It followed an open-label study design with consecutive treatment cohorts. Consecutive groupings of 67 patients with treatment-resistant major depressive disorder and with baseline suicidality present were treated for up to 24 treatments. The study was run from February 2012 through June 2019. Patients were followed up for 6 months at the end of the treatment period. This post hoc secondary analysis of the trial was performed from January to November 2019. Interventions:MST was delivered at 100% stimulator output over the prefrontal cortex with low (25 Hz), moderate (50 or 60 Hz), or high (100 Hz) frequency, for a maximum of 24 sessions. Main Outcomes and Measures:Remission from suicidality was measured as an end point score of 0 on the Beck Scale for Suicidal Ideation. A linear mixed model was used to assess the trajectory of Beck Scale for Suicidal Ideation scores. Results:A total of 67 patients (mean [SD] age, 46.3 [13.6] years; 40 women [60.0%]) received a mean (SD) of 19.5 (5.1) MST treatments. The overall number of patients achieving remission was 32 (47.8%). Sixteen patients (55.2%) receiving low-frequency MST achieved remission, as well as 12 patients (54.5%) in the moderate-frequency group, and 4 patients (25.0%) in the high-frequency group. The linear mixed model revealed an association of time with Beck Scale for Suicidal Ideation scores (F8,293.95?=?5.73; P?<?.001). Conclusions and Relevance:These findings suggest that MST may be an effective treatment for suicidality, and sensitivity analysis shows this may be particularly so at low and moderate frequencies. Future studies should directly compare MST with electroconvulsive therapy for treating suicidality and should evaluate MST as a treatment for suicidality across mental disorders. Trial Registration:ClinicalTrials.gov Identifier: NCT01596608.

Project description:Functional seizures, a primary subtype of functional neurological disorder (FND), are a known cause of serious neurological disability with an increasing awareness of their impact amongst the neuroscience community. Situated at the intersection of neurology and psychiatry, FND is characterized by a range of alterations in motor, sensory or cognitive performance, such as abnormal movements, limb weakness, and dissociative, seizure-like episodes. Functional seizures are known, in part, to have psychological underpinnings; however, the lack of effective and consistent treatment options requires research and novel approaches to better understand the etiology, diagnosis and what constitutes a successful intervention. Ketamine, a selective blocker of the N-methyl-D-aspartate receptor, has a well-established safety and efficacy profile. In recent years, ketamine-assisted therapy has shown increasing potential for treating a broad range of psychiatric conditions, building on its demonstrated rapid-acting antidepressant effects. Here we present a 51-year-old female with refractory daily functional seizures leading to significant disability and a medical history significant for major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). After unsuccessful treatment attempts, the patient underwent a novel protocol with ketamine-assisted therapy. After 3 weeks of ketamine-assisted therapy followed by 20 weeks of intermittent ketamine treatment and ongoing integrative psychotherapy, the patient's seizures were significantly reduced in frequency and severity. She experienced significant improvements in depressive symptoms and functional ability scores. To our knowledge, this is the first reported case describing improvement in functional seizures following ketamine-assisted therapy. While rigorous studies are needed, this case report encourages further investigation of ketamine-assisted therapy for functional seizures and other functional neurological symptoms.

Project description:BackgroundElectroconvulsive therapy (ECT) is well-established and effective for treatment-resistant depression (TRD), but in Canada and the USA, less than 1% of patients with TRD receive ECT mainly due to its cognitive adverse effects (i.e. amnesia). Thus, new treatment alternatives for TRD are urgently needed. One such treatment is magnetic seizure therapy (MST). ECT involves applying a train of high-frequency electrical stimuli to induce a seizure, whereas MST involves applying a train of high-frequency magnetic stimuli to induce a seizure.MethodsIn this manuscript, we introduce our international, two-site, double-blinded, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. This trial will compare the efficacy of MST to right unilateral ultra-brief pulse width electroconvulsive therapy (RUL-UB-ECT) with a combined primary endpoint of remission of depression and superior cognitive adverse effects in 260 patients with TRD. Amelioration of suicidal ideation will be assessed as a secondary endpoint. Inpatients or outpatients, over 18 years of age with a MINI International Neuropsychiatric Interview (MINI) diagnosis of non-psychotic major depressive disorder (MDD) can be enrolled in the study provided that they meet illness severity and full eligibility criteria. Participants are randomized to receive MST or RUL-UB ECT, 2-3 days per week over seven weeks, or a maximum of 21 treatments. The study will involve before-, during-, and after-treatment assessments of depression severity, suicidal ideation, subjective side-effects, and cognitive performance consistent with an intent-to-treat study design approach.DiscussionPositive results from this trial could have an immediate and tremendous impact for patients with TRD. If MST demonstrates comparable antidepressant treatment efficacy to ECT, but with greater cognitive safety, it could rapidly be adopted into clinical practice. Indeed, given that the administration of MST is nearly identical to ECT, the majority of ECT facilities in North America could readily adopt MST. Furthermore, the potential for cognitive safety could lead to improved treatment acceptability. Healthcare providers, patients and care partners, and policymakers would therefore demand this form of convulsive therapy.Trial statusEnrollment for this study began on June 26, 2018, and is estimated to complete recruitment by July 2024. At the time of submission, we have enrolled and randomized 117 participants.Trial registrationClinicalTrials.gov NCT03191058 , Registered on June 19, 2017. Primary sponsor: Daniel Blumberger (DMB), Principal Investigator Daniel.Blumberger@camh.ca , 416-535-8501 x 33662 Contact for public queries: DMB, Daniel.Blumberger@camh.ca Contact for scientific queries: ZJD, Zdaskalakis@health.ucsd.edu.

Project description:Therapeutic seizures may work for treatment-resistant depression (TRD) by producing neuroplasticity. We evaluated whether magnetic seizure therapy (MST) produces changes in suicidal ideation and neuroplasticity as indexed through transcranial magnetic stimulation and electroencephalography (TMS-EEG) of the dorsolateral prefrontal cortex (DLPFC). Twenty-three patients with TRD were treated with MST. Changes in suicidal ideation was assessed through the Scale for Suicidal Ideation (SSI). Before and after the treatment course, neuroplasticity in excitatory and inhibitory circuits was assessed with TMS-EEG measures of cortical-evoked activity (CEA) and long-interval cortical inhibition (LICI) from the left DLPFC, and the left motor cortex as a control condition. As in our previous report, the relationship between TMS-EEG measures and suicidal ideation was examined with the SSI. Results show that 44.4% of patients experienced resolution of suicidal ideation. Based on DLPFC assessment, MST produced significant CEA increase over the frontal central electrodes (cluster p < 0.05), but did not change LICI on a group level. MST also reduced the SSI scores (p < 0.005) and the amount of reduction correlated with the decrease in LICI over the right frontal central electrodes (cluster p < 0.05; rho = 0.73 for Cz). LICI change identified patients who were resolved of suicidal ideation with 90% sensitivity and 88% specificity (AUC = 0.9, p = 0.004). There was no significant finding with motor cortex assessment. Overall, MST produced significant rates of resolution of suicidal ideation. MST also produced neuroplasticity in the frontal cortex, likely through long-term potentiation (LTP)-like mechanisms. The largest reduction in suicidal ideation was demonstrated in patients showing concomitant decreases in cortical inhibition-a mechanism linked to enhanced LTP-like plasticity. These findings provide insights into the mechanisms through which patients experience resolution of suicidal ideation following seizure treatments in depression.

Dataset Information

Magnetic seizure therapy in an adolescent with refractory bipolar depression: a case report.

Publications

Magnetic seizure therapy in an adolescent with refractory bipolar depression: a case report.

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