Adjunctive Magnetic Seizure Therapy for Schizophrenia: A Systematic Review

Objective: The efficacy and safety of adjunctive magnetic seizure therapy (MST) for patients with schizophrenia are unclear. This systematic review was conducted to examine the efficacy and safety of adjunctive MST for schizophrenia.Methods: Chinese (WanFang and Chinese Journal Net) and English (PubMed, EMBASE, PsycINFO, and the Cochrane Library) databases were systematically searched.Results: Two open-label self-controlled studies (n = 16) were included and analyzed in this review. In these studies, the Positive and Negative Syndrome Scale (PANSS) total scores and Brief Psychiatric Rating Scale (BPRS) total scores significantly decreased from baseline to post-MST (all Ps < 0.05), without serious adverse neurocognitive effects. Mixed findings on the neurocognitive effects of adjunctive MST for schizophrenia were reported in the two studies. A discontinuation rate of treatment of up to 50% (4/8) was reported in both studies. The rate of adverse drug reactions (ADRs) was evaluated in only one study, where the most common ADRs were found to be dizziness (25%, 2/8) and subjective memory loss (12.5%, 1/8).Conclusion: There is inconsistent evidence for MST-related adverse neurocognitive effects and preliminary evidence for the alleviation of psychotic symptoms in schizophrenia.

Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST): protocol for identification of novel biomarkers via neurophysiology

Background Electroconvulsive therapy (ECT) is the most effective treatment for treatment-resistant depression (TRD), especially for acute suicidal ideation, but the associated cognitive adverse effects and negative stigma limit its use. Another seizure therapy under development is magnetic seizure therapy (MST), which could potentially overcome the restrictions associated with ECT with similar efficacy. The neurophysiological targets and mechanisms of seizure therapy, however, remain poorly understood. Methods/design This neurophysiological study protocol is published as a companion to the overall Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST) protocol that describes our two-site, double-blind, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. Our aim for the neurophysiological component of the study is to evaluate two biomarkers, one to predict remission of suicidal ideation (primary outcome) and the other to predict cognitive impairment (secondary outcome). Suicidal ideation will be assessed through cortical inhibition, which according to our preliminary studies, correlates with remission of suicidal ideation. Cortical inhibition will be measured with simultaneous transcranial magnetic stimulation (TMS) and electroencephalography (EEG), TMS-EEG, which measures TMS-evoked EEG activity. Cognitive adverse effects associated with seizure therapy, on the contrary, will be evaluated via multiscale entropy analysis reflecting the complexity of ongoing resting-state EEG activity. Discussion ECT and MST are known to influence cortical inhibition associated with depression, suicidal ideation severity, and clinical outcome. Therefore, evaluating cortical inhibition and brain temporal dynamics will help understand the pathophysiology of depression and suicidal ideation and define new biological targets that could aid clinicians in diagnosing and selecting treatments. Resting-state EEG complexity was previously associated with the degree of cognitive side effects after a seizure therapy. This neurophysiological metric may help clinicians assess the risk for adverse effects caused by these useful and effective treatments. Trial registration ClinicalTrials.govNCT03191058. Registered on June 19, 2017.

Magnetic Seizure Therapy Compared to Electroconvulsive Therapy for Schizophrenia: A Randomized Controlled Trial

Background: Magnetic seizure therapy (MST) is a potential alternative to electroconvulsive therapy (ECT). However, reports on the use of MST for patients with schizophrenia, particularly in developing countries, which is a main indication for ECT, are limited.Methods: From February 2017 to July 2018, 79 inpatients who met the DSM-5 criteria for schizophrenia were randomized to receive 10 sessions of MST (43 inpatients) or ECT (36 inpatients) over the course of 4 weeks. At baseline and 4-week follow-up, the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to assess symptom severity and cognitive functions, respectively.Results: Seventy-one patients who completed at least half of the treatment protocol were included in the per-protocol analysis. MST generated a non-significant larger antipsychotic effect in terms of a reduction in PANSS total score [g = 0.17, 95% confidence interval (CI) = −0.30, 0.63] and response rate [relative risk (RR) = 1.41, 95% CI = 0.83–2.39]. Twenty-four participants failed to complete the cognitive assessment as a result of severe psychotic symptoms. MST showed significant less cognitive impairment over ECT in terms of immediate memory (g = 1.26, 95% CI = 0.63–1.89), language function (g =1.14, 95% CI = 0.52–1.76), delayed memory (g = 0.75, 95% CI = 0.16–1.35), and global cognitive function (g = 1.07, 95% CI = 0.45–1.68). The intention-to-treat analysis generated similar results except for the differences in delayed memory became statistically insignificant. Better baseline cognitive performance predicted MST and ECT response.Conclusions: Compared to bitemporal ECT with brief pulses and age-dose method, MST had similar antipsychotic efficacy with fewer cognitive impairments, indicating that MST is a promising alternative to ECT as an add-on treatment for schizophrenia.Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT02746965.

Comparative efficacy and cognitive function of magnetic seizure therapy vs. electroconvulsive therapy for major depressive disorder: a systematic review and meta-analysis

Magnetic seizure therapy (MST) has established efficacy in the treatment of depression and a growing evidence base in the treatment of depression. We conducted the first systematic review and meta-analysis of the efficacy of MST in anti-depressive treatment and its impact on cognitive function (INPLASY registration number: INPLASY202170061). We searched for controlled trials published in English between 1 January 2001 to 31 December 2020 in PubMed, EMBASE, Cochrane Library, Web of Science, and PsycINFO databases. The evaluation process strictly followed the Cochrane bias risk assessment tool into the literature, and Meta-analysis was performed according to the Cochrane System Reviewer’s Manual. Data from a total of 285 patients from 10 studies were retained in the quantitative synthesis. The results showed no significant difference between MST and ECT in the antidepressant effect (SDM −0.13 [−0.78;0.52]). Compared with ECT, MST showed shorter recovery time (MD −5.67 [−9.75; −1.60]) and reorientation time (MD −14.67 [−27.96; −1.41]); and MST showed less cognitive impairment on the immediate recall of words (SDM 0.80 [0.35;1.25]), delayed recall of words (SDM 0.99 [0.01;0.74]), visual-spatial immediate memory (SDM 0.51 [0.20;0.83]), visual-spatial delayed memory (SDM 0.57 [0.11;1.02]), and the verbal fluency (SDM 0.51 [0.20;0.83]). Our evidence-based study is the first meta-analysis on the efficacy of MST in anti-depressive treatment and its effect on cognitive function. It showed that the curative effect of MST in anti-depressive treatment is equivalent to that of ECT. Besides, depressive patients with MST benefit more from cognitive function compared with ECT.

A Systematic Review of Neuromodulation Treatment Effects on Suicidality

Introduction: Neuromodulation is an important group of therapeutic modalities for neuropsychiatric disorders. Prior studies have focused on efficacy and adverse events associated with neuromodulation. Less is known regarding the influence of neuromodulation treatments on suicidality. This systematic review sought to examine the effects of various neuromodulation techniques on suicidality.Methods: A systematic review of the literature from 1940 to 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was conducted. Any reported suicide-related outcome, including suicidal ideation, suicide intent, suicide attempt, completed suicide in reports were considered as a putative measure of treatment effect on suicidality.Results: The review identified 129 relevant studies. An exploratory analysis of a randomized controlled trial comparing the effects of sertraline and transcranial direct-current stimulation (tDCS) for treating depression reported a decrease in suicidal ideation favoring tDCS vs. placebo and tDCS combined with sertraline vs. placebo. Several studies reported an association between repetitive transcranial magnetic stimulation and improvements in suicidal ideation. In 12 of the studies, suicidality was the primary outcome, ten of which showed a significant improvement in suicidal ideation. Electroconvulsive therapy (ECT) and magnetic seizure therapy was also shown to be associated with lower suicidal ideation and completed suicide rates. There were 11 studies which suicidality was the primary outcome and seven of these showed an improvement in suicidal ideation or suicide intent and fewer suicide attempts or completed suicides in patients treated with ECT. There was limited literature focused on the potential protective effect of vagal nerve stimulation with respect to suicidal ideation. Data were mixed regarding the potential effects of deep brain stimulation on suicidality.Conclusions: Future prospective studies of neuromodulation that focus on the primary outcome of suicidality are urgently needed.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=125599, identifier: CRD42019125599.

Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST – MST): Study Protocol for a Randomized Non-Inferiority Trial of Magnetic Seizure Therapy versus Electroconvulsive Therapy

BackgroundElectroconvulsive therapy (ECT) is well-established and effective for treatment resistant depression (TRD), but in Canada and the United States, 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 RegistrationClinical Trials Gov NCT03191058, Registered June 19, 2017