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Magnetic seizure therapy (MST) for major depressive disorder.

ABSTRACT: Electroconvulsive therapy (ECT) is effective for major depressive disorder (MDD) but its effects on memory limit its widespread use. Magnetic seizure therapy (MST) is a potential alternative to ECT that may not adversely affect memory. In the current trial, consecutive patients with MDD consented to receive MST applied over the prefrontal cortex according to an open-label protocol. Depressive symptoms and cognition were assessed prior to, during and at the end of treatment. Patients were treated two to three times per week with high-frequency MST (i.e., 100?Hz) (N?=?24), medium frequency MST (i.e., 60 or 50?Hz) (N?=?26), or low-frequency MST (i.e., 25?Hz MST) (N?=?36) using 100% stimulator output. One hundred and forty patients were screened; 86 patients with MDD received a minimum of eight treatments and were deemed to have an adequate course of MST; and 47 completed the trial per protocol, either achieving remission (i.e., 24-item Hamilton Rating Scale for Depression score <10 and a relative reduction of >60% at two consecutive assessments; n?=?17) or received a maximum of 24 sessions (n?=?30). High-frequency (100?Hz) MST produced the highest remission rate (33.3%). Performance on most cognitive measures remained stable, with the exception of significantly worsened recall consistency of autobiographical information and significantly improved brief visuospatial memory task performance. Under open conditions, MST led to clinically meaningful reduction in depressive symptoms in patients with MDD and produced minimal cognitive impairment. Future studies should compare MST and ECT under double-blind randomized condition.

SUBMITTER: Daskalakis ZJ

PROVIDER: S-EPMC6901571 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Magnetic seizure therapy (MST) for major depressive disorder.

Daskalakis Zafiris J ZJ Dimitrova Julia J McClintock Shawn M SM Sun Yinming Y Voineskos Daphne D Rajji Tarek K TK Goldbloom David S DS Wong Albert H C AHC Knyahnytska Yuliya Y Mulsant Benoit H BH Downar Jonathan J Fitzgerald Paul B PB Blumberger Daniel M DM

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20190905 2

Electroconvulsive therapy (ECT) is effective for major depressive disorder (MDD) but its effects on memory limit its widespread use. Magnetic seizure therapy (MST) is a potential alternative to ECT that may not adversely affect memory. In the current trial, consecutive patients with MDD consented to receive MST applied over the prefrontal cortex according to an open-label protocol. Depressive symptoms and cognition were assessed prior to, during and at the end of treatment. Patients were treated ...[more]

PMID: 31486777

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Project description:ImportanceElectroconvulsive therapy (ECT) is highly effective and rapid in treating depression, but it carries a risk of significant cognitive adverse effects. Magnetic seizure therapy (MST), an investigational antidepressant treatment, may maintain the robust antidepressant efficacy of ECT while substantially reducing adverse effects due to its enhanced focality and weaker stimulation strength; however, previous clinical trials of MST were limited by small sample sizes.ObjectiveTo compare the antidepressant efficacy of MST vs ultrabrief pulse right unilateral (RUL) ECT.Design, setting, and participantsA between-participants, double-blinded, randomized clinical trial was conducted at 3 academic hospitals from June 2007 to August 2012. Adults aged 18 to 90 years who were referred for treatment with ECT, had a major depressive episode in the context of major depressive disorder or bipolar disorder, and had a baseline 24-item Hamilton Depression Rating Scale (HDRS-24) total score of 18 or higher were included. Participants were randomly assigned 1:1 to treatment with MST or ultrabrief pulse RUL ECT. After the treatment course, patients were naturalistically followed up for up to 6 months to examine the durability of clinical effects.InterventionsTreatment with MST, applied at 100 Hz at 100% of the maximum device power for 10 seconds, or ultrabrief pulse RUL ECT, applied at 6 times seizure threshold.Main outcomes and measuresThe primary outcome was change from baseline in HDRS-24 total score, with patients followed up for up to 6 months. A reduction of at least 50% in the HDRS-24 score indicated response, and at least a 60% decrease in the HDRS-24 score and a total score of 8 or less indicated remission.ResultsOf the 73 participants (41 [56.2%] female; mean [SD] age, 48 [14.1] years), 35 were randomized to MST and 38 to ECT. Among them, 53 (72.6%) were classified as completers (29 in the MST group and 24 in the ECT group). Both MST and ECT demonstrated clinically meaningful antidepressant effects. In the intent-to-treat sample, 18 participants (51.4%) in the MST group and 16 (42.1%) in the ECT group met response criteria; 13 (37.1%) in the MST group and 10 (26.3%) in the ECT group met remission criteria. Among completers, 17 of 29 (58.6%) in the MST group and 15 of 24 (62.5%) in the ECT group met response criteria; 13 of 29 (44.8%) in the MST group and 10 of 24 (41.7%) in the ECT group met remission criteria. There was no significant difference between MST and ECT for either response or remission rates. However, the mean (SD) number of treatments needed to achieve remission was 9.0 (3.1) with MST and 6.7 (3.3) with ECT, a difference of 2.3 treatments (t71.0 = 3.1; P = .003). Both MST and ECT showed a sustained benefit over a 6-month follow-up period, again with no significant difference between them. Compared with MST, ECT had significantly longer time to orientation after treatment (threshold level: F1,56 = 10.0; P = .003) and greater severity of subjective adverse effects, particularly in the physical and cognitive domains.Conclusions and relevanceThis randomized clinical trial found that the efficacy of MST was indistinguishable from that of ultrabrief pulse RUL ECT, the safest form of ECT currently available. These results support the continued development of MST and provide evidence for advantages relative to state-of-the-art ECT.Trial registrationClinicalTrials.gov Identifier: NCT00488748.

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:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

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Magnetic seizure therapy (MST) for major depressive disorder.

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Magnetic seizure therapy (MST) for major depressive disorder.

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