Preliminary Guidelines for Resuming Electroconvulsive Therapy After a Complication of Status Epilepticus.

ABSTRACT: Electroconvulsive therapy (ECT) is an effective and safe treatment for severe major depressive disorder. However, status epilepticus is a rare yet serious complication that can occur following treatment. We present a case of a patient with severe major depression who experienced convulsive status epilepticus during the first treatment of her fourth ECT course. Electroconvulsive therapy treatment was then discontinued, and the patient underwent unsuccessful medication trials. Due to deterioration of depressive symptoms, ECT resumption was considered 3 months later after the patient had been maintained on an antiepileptic drug and no further seizures had occurred. Electroconvulsive therapy was resumed with a detailed safety protocol that included electroencephalographic monitoring before and after ECT treatment, remaining on an antiepileptic drug during the course of treatment, performing ECT in the operating room, and preparing seizure-terminating drugs before each treatment. The patient completed her ECT course with no tardive seizures or other neurological complications. We present the safety measures taken for resumption of ECT in our patient, and we offer preliminary clinical guidelines for resuming ECT after a complication of status epilepticus.

Trajectory Modeling and Response Prediction in Transcranial Magnetic Stimulation for Depression.

Repetitive transcranial magnetic stimulation (rTMS) therapy could be improved by better and earlier prediction of response. Latent class mixture (LCMM) and non-linear mixed effects (NLME) modelling have been applied to model the trajectories of antidepressant response (or non-response) to TMS, but it is not known whether such models can predict clinical outcomes. We compared LCMM and NLME approaches to model the antidepressant response to TMS in a naturalistic sample of 238 patients receiving rTMS for treatment resistant depression (TRD), across multiple coils and protocols. We then compared the predictive power of those models. LCMM trajectories were influenced largely by baseline symptom severity, but baseline symptoms provided little predictive power for later antidepressant response. Rather, the optimal LCMM model was a nonlinear two-class model that accounted for baseline symptoms. This model accurately predicted patient response at 4 weeks of treatment (AUC = 0.70, 95% CI = [0.52-0.87]), but not before. NLME offered slightly improved predictive performance at 4 weeks of treatment (AUC = 0.76, 95% CI = [0.58 - 0.94], but likewise, not before. In showing the predictive validity of these approaches to model response trajectories to rTMS, we provided preliminary evidence that trajectory modeling could be used to guide future treatment decisions.

Structural Racism in Psychiatric Research Careers: Eradicating Barriers to a More Diverse Workforce.

Investigators from minoritized backgrounds are underrepresented in psychiatric research. That underrepresentation contributes to disparities in outcomes of access to mental health care. Drawing on lived experience, scholarly qualitative reports, and empirical data, the authors review how the underrepresentation of minoritized researchers arises from interlocking, self-reinforcing effects of structural biases in our research training and funding institutions. Minoritized researchers experience diminished early access to advanced training and opportunities, stereotype threats and microaggressions, isolation due to lack of peers and senior mentors, decreased access to early funding, and unique community and personal financial pressures. These represent structural racism-a system of institutional assumptions and practices that perpetuates race-based disparities, in spite of those institutions' efforts to increase diversity and in contradiction to the values that academic leaders outwardly espouse. The authors further review potential approaches to reversing these structural biases, including undergraduate-focused research experiences, financial support for faculty who lead training/mentoring programs, targeted mentoring through scholarly societies, better use of federal diversity supplement funding, support for scientific reentry, cohort building, diversity efforts targeting senior leadership, and rigorous examination of hiring, compensation, and promotion practices. Several of these approaches have empirically proven best practices and models for dissemination. If implemented alongside outcome measurement, they have the potential to reverse decades of structural bias in psychiatry and psychiatric research.

Physiologically informed neuromodulation.

The rapid evolution of neuromodulation techniques includes an increasing amount of research into stimulation paradigms that are guided by patients' neurophysiology, to increase efficacy and responder rates. Treatment personalisation and target engagement have shown to be effective in fields such as Parkinson's disease, and closed-loop paradigms have been successfully implemented in cardiac defibrillators. Promising avenues are being explored for physiologically informed neuromodulation in psychiatry. Matching the stimulation frequency to individual brain rhythms has shown some promise in transcranial magnetic stimulation (TMS). Matching the phase of those rhythms may further enhance neuroplasticity, for instance when combining TMS with electroencephalographic (EEG) recordings. Resting-state EEG and event-related potentials may be useful to demonstrate connectivity between stimulation sites and connected areas. These techniques are available today to the psychiatrist to diagnose underlying sleep disorders, epilepsy, or lesions as contributing factors to the cause of depression. These technologies may also be useful in assessing the patient's brain network status prior to deciding on treatment options. Ongoing research using invasive recordings may allow for future identification of mood biomarkers and network structure. A core limitation is that biomarker research may currently be limited by the internal heterogeneity of psychiatric disorders according to the current DSM-based classifications. New approaches are being developed and may soon be validated. Finally, care must be taken when incorporating closed-loop capabilities into neuromodulation systems, by ensuring the safe operation of the system and understanding the physiological dynamics. Neurophysiological tools are rapidly evolving and will likely define the next generation of neuromodulation therapies.

Systematic review of preservation TMS that includes continuation, maintenance, relapse-prevention, and rescue TMS.

BACKGROUND: A dearth of evidence-based information exists to guide the delivery of transcranial magnetic stimulation (TMS) after a successful acute course of treatment for Major Depressive Disorder. METHODS: To provide guidance for clinicians, existing literature focused on "preservation TMS" was systematically reviewed and synthesized. Preservation TMS was defined as TMS used to sustain a clinical response after a successful acute course of treatment and included reports using the terms maintenance, continuation, relapse prevention, or rescue TMS. The review protocol was registered on Open Science Framework and reported following PRISMA guidelines. Data were abstracted by two authors and discrepancies were resolved by a third author. Primary outcome measures focused on clinical efficacy. The evaluated studies were graded using the Levels of Evidence criteria published by the Oxford Centre for Evidence-Based Medicine. RESULTS: The search included 536 abstracts and 16 additional papers, from which 63 full articles were screened. Data were abstracted from 30 qualifying sources (N=1,494) including 4 randomized controlled trials (one sham controlled), 14 open trials, and 12 case series. Overall, the quality of existing literature was low regarding efficacy but provided clear support for effectiveness and safety across a range of preservation TMS protocols based on mostly uncontrolled studies. CONCLUSIONS: Existing literature suggests that preservation TMS protocols significantly vary and are mostly supported by open trials and case series. Due to a lack of effective alternatives, preservation TMS will likely be required for certain patients who respond to acute TMS therapy. More studies of preservation TMS are critically needed.

Virus-encoded b7-2 costimulation molecules enhance the protective capacity of a replication-defective herpes simplex virus type 2 vaccine in immunocompetent mice.

Herpes simplex virus 2 (HSV-2) and, to a lesser extent, HSV-1 cause the majority of sexually transmitted genital ulcerative disease. No effective prophylactic vaccine is currently available. Replication-defective HSV stimulates immune responses in animals but produces no progeny virus, making it potentially useful as a safe form of live vaccine against HSV. Because it does not replicate and spread in the host, however, replication-defective virus may have relatively limited capacity to solicit professional antigen presentation. We previously demonstrated that in mice devoid of B7-1 and B7-2 costimulation molecules, replication-defective HSV-2 encoding B7-1 or B7-2 induces stronger immune responses and protection against HSV-2 challenge than immunization with replication-defective virus alone. Here, we vaccinated wild-type mice fully competent to express endogenous B7 costimulation molecules with replication-defective HSV-2 or replication-defective virus encoding B7-2 and compared their capacities to protect against vaginal HSV-2 infection and disease. Replication-defective virus encoding B7-2 induced more IFN-gamma-producing CD4 T cells than did replication-defective virus alone. Immunization with B7-2-expressing virus decreased challenge virus replication in the vaginal mucosa, genital and neurological disease, and mortality more effectively than did immunization with the parental replication-defective virus. Prior immunization with B7-expressing, replication-defective virus also effectively suppressed infection of the nervous system compared to immunization with the parental virus. Thus, B7 costimulation molecules expressed at the site of HSV infection can enhance vaccine efficacy even in a fully immunocompetent host.