Innovations in clinical neuroscience最新文献

Objective: Compared to the general population, the risk of suicide is three times higher in patients with epilepsy and remains doubled for these patients even after adjusting for sociodemographic correlates of suicide in the absence of mental health comorbidities. Following the United States (US) Food and Drug Administration (FDA) alert prompting a black box warning regarding the association between suicidality and antiepileptic drugs (AEDs), several studies were conducted, the results of which have been ambiguous, with some demonstrating a positive association between suicidality and AEDs, while others did not. This systematic review of literature sought to study the relationship between suicidality and AEDs when used exclusively for treatment of epilepsy.

Methods: A comprehensive literature search was conducted on PubMed without time limits using a predefined search language. The search results were then subjected to a systematic screening process. Eight out of a total of 443 articles satisfying predefined inclusion and exclusion criteria were included in the review for final data extraction.

Results: Three studies found a significant association between suicide-related behavior and levetiracetam use in the treatment of epilepsy. One study reported a positive association of pregabalin use in patients with epilepsy under 40 years of age and high AED load with suicidality, independent of depression. The remaining four studies reported a significant association between positive family and personal history of psychiatric comorbidities and suicidality in epilepsy.

Conclusion: Although there were several methodological limitations, this review found an association between levetiracetam use and mental health comorbidities and the occurrence of suicidality in epilepsy. Larger prospective, randomized studies that overcome the limitations of current studies are required to provide definitive evidence on the occurrence of suicidality in patients with epilepsy and AED use.

Background: Migraine is a common neurovascular disorder with a pathophysiology related to the serotonin (5-hydroxytryptamine; 5-HT) system. Pharmacologic modulation of 5-HT receptors has demonstrated efficacy in the acute treatment of migraines. Psilocybin, a classic psychedelic with 5-HT receptor activity, has demonstrated therapeutic potential in the management of neuropsychiatric conditions. To date, no reports have investigated the effect of psilocybin administered acutely during a migraine episode.

Case presentation: The case of a 33-year-old male patient with a history of migraines with aura, who had acute administration of oral psilocybin (in the form of the dried fruiting body of Psilocybe cubensis mushrooms) at migraine onset is presented. Headache intensity was rated hourly using the Numerical Rating Scale (NRS) and compared to three previous migraines. Profound reductions in headache intensity and emetic episodes were reported during the migraine treated acutely with oral psilocybin administration, compared to three previous migraines.

Discussion: The severe, disabling, and treatment-resistant nature of migraines warrants continued surveillance for novel pharmacologic interventions. The established congruous pathophysiology of migraine and pharmacology of psilocybin, via the 5-HT receptor system, positions psilocybin as a potential therapeutic target.

Conclusion: While this report highlights the potential role of psilocybin in the acute management of migraines, it is essential to note that it should not be considered a basis for guiding clinical practice at this point. Further research is necessary to establish the safety and efficacy of psilocybin as a treatment option for migraines.

This article expands on a session, titled "Patient Centricity: Design and Conduct of Clinical Trials in Orphan Diseases," that was presented as part of a two-day meeting on Pediatric Drug Development at the International Society for Central Nervous System (CNS) Clinical Trials and Methodology (ISCTM) Autumn Conference in Boston, Massachusetts, in October 2020. Speakers from various areas of pediatric drug development addressed a variety of implications of including children in drug development programs, including implications for rare/orphan diseases. The speakers have written summaries of their talks. The session's lead Chair was Dr. Joan Busner, who wrote introductory and closing comments. Dr. Simon Day, regulatory consultant, outlined some of the past mistakes that have plagued trials that did not consult with patient groups in the early design phase. Dr. Atul Mahableshwarkar provided an industry perspective of a recent trial that benefited from the inclusion of patient input. Drs. Lucas Kempf and Maria Sheean provided regulatory input from the perspectives of the United States (US) Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively. Dr. Judith Dunn outlined a novel approach for assessing and rank ordering patient and clinician clinical meaningfulness and the disconnect that may occur. Dr. Busner provided closing comments, tied together the presented issues, and provided a synopsis of the lively discussion that followed the session. In addition to the speakers above, the discussion included two representatives from patient advocacy groups, as well as an additional speaker who described the challenges of conducting a pediatric trial in the US and European Union (EU), given the often competing regulatory requirements. This article should serve as an expert-informed reference to those interested and involved in CNS drug development programs that are aimed at children and rare diseases and seek to ensure a patient-centric approach.

Music is an auditory stimulus of a complex nature, as many perceptive processes develop simultaneously in various areas of the brain. The same brain areas are involved in processing music and movement rhythms, which is why music can be used in the rehabilitation of movement disorders. There is growing evidence that music-assisted treadmill training can be effective in treating Parkinson's disease (PD) gait disorders, as auditory cueing with treadmill training may specifically work on those motor areas, including the cerebellum, that are not affected by the disease. Thus, music-therapy, when properly applied, could pave the way for better management of motor symptoms in PD.

This article expands upon a session, titled "Implications of Pediatric Initiatives on CNS Drug Development for All Ages-2020 and Beyond," that was presented as part of a two-day meeting on pediatric drug development at the International Society for Central Nervous System (CNS) Clinical Trials and Methodology (ISCTM) Autumn Conference in Boston, Massachusetts, in October 2020. Speakers from various areas of pediatric drug development addressed a variety of implications of including children in drug development programs. The speakers wrote summaries of their talks, which are included here. The session's lead chair was Dr. Gahan Pandina, who wrote introductory and closing comments. Dr. Joseph Horrigan addressed the current landscape of pediatric development programs. Dr. Gahan Pandina addressed how the approach to research in pediatric populations affects the drug development process and vice versa. Dr. Alison Bateman-House discussed the ethical implications of research in the pediatric population. Dr. Luca Pani discussed some of the global regulatory issues and challenges concerning research in pediatric patients. Dr. Judith Kando served as a discussant and posed new questions about means of facilitating pediatric research. Finally, Dr. Gahan Pandina provided closing comments and tied together the presented issues. This paper should serve as an expert-informed reference to those interested and involved in CNS drug development programs that are aimed at children and/or required, through regulations, to include children as part of the approval process.

Objective: Individuals with serious mental illness (SMI) are recognized to be among the highest risk patients to experience more severe symptoms of COVID-19, not only due to poor baseline health and associated disparity, but also due to medications prescribed to manage their illness that are known to compromise immunity even further. Clozapine, a gold standard antipsychotic used in the treatment for refractory schizophrenia, is considered to be the antipsychotic with the greatest risk of compromising immunity due to its potential to cause blood dyscrasia, including leukopenia and rarely, but potentially, agranulocytosis. The objective of this study is to determine if there is any potential hematological consequence for the use of COVID-19 messenger ribonucleic acid (mRNA) vaccines or the impact of active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients receiving clozapine therapy. Since there is controversy over the rate of vaccine hesitancy in patients with SMI, we also examined the rate of vaccine acceptance in our subject population.

Design: This study was a retrospective chart review conducted at a 160-bed state psychiatric inpatient hospital in upstate New York evaluating the impact of COVID-19 vaccination, SARS-CoV-2 infection, and vaccine acceptance in patients prescribed clozapine.

Results: Both the administration of COVID-19 mRNA vaccines and SARS-CoV-2 infection did not appear to significantly influence the hematologic values that are monitored by the United States (US) Food and Drug Administration (FDA) to ensure safe use of clozapine. When offered vaccination, most patients hospitalized for SMI were willing to accept it.

Conclusion: With the likelihood of COVID-19 mRNA vaccinations becoming a recommended routine vaccination, requiring periodic boosters, patients receiving clozapine therapy have been observed to not be at higher risk of adverse hematological consequences when the mRNA vaccine is administered. Furthermore, inpatient psychiatry settings should be considered an optimal site of vaccination to improve vaccination efforts in our communities.

Bupropion has been in use for several decades. It is widely used for major depressive disorder (MDD), seasonal affective disorder (SAD), and smoking cessation. It is also a treatment of choice for mild-to-moderate depression and is prescribed for atypical and melancholic depression. However, bupropion overdose can lead to serious neurological and cardiovascular adverse effects. We report a recent case of bupropion overdose and review published cases in the literature to present the spectrum of clinical findings and treatments used to overcome the effects of bupropion overdose. Per our findings, bupropion doses of 2.7g and upward can lead to seizures and cause encephalopathy and cardiovascular effects. Higher doses could also lead to intubation and increased hospital stay. Therefore, patients with an increased risk of cardiovascular issues and seizures should be evaluated before starting the medication or increasing the dosage.

This ongoing column is dedicated to providing information to our readers on managing legal risks associated with medical practice. We invite questions from our readers. The answers are provided by PRMS (www.prms.com), a manager of medical professional liability insurance programs with services that include risk management consultation and other resources offered to health care providers to help improve patient outcomes and reduce professional liability risk. The answers published in this column represent those of only one risk management consulting company. Other risk management consulting companies or insurance carriers might provide different advice, and readers should take this into consideration. The information in this column does not constitute legal advice. For legal advice, contact your personal attorney. Note: The information and recommendations in this article are applicable to physicians and other health care professionals so "clinician" is used to indicate all treatment team members.

Existential issues are common in patient experiences and can present as themes in any practice setting, but particularly in psychotherapy. Existential issues are any concerns that arise from distress or questions about difficult subjects, such as death, meaning, freedom, and isolation, and can be a source of psychiatric concerns or simply a modifying factor. Because of this, clinicians should be able to recognize and understand the basic tenets of addressing existential issues in psychotherapy. This article outlines the historical context and theoretical basis of existentialism. It also discusses existential issues in relation to psychotherapy and provides practical clinical tips for addressing these issues with patients, including helpful probing questions, tips for noticing existential themes, and ideas about how to address existential issues in session.

Depersonalization and derealization refer to an estranged state of mind that involves a profound feeling of detachment from one's sense of self and the surrounding environment, respectively. The phenomena co-occur on a continuum of severity, ranging from a transient experience as a normal reaction to a traumatic event to a highly debilitating condition with persistent symptoms, formally described as depersonalization/derealization disorder (DPDR). Lack of awareness of DPDR is partly due to a limited neurobiological framework, and there remains a significant risk of misdiagnosis in clinical practice. Earlier literature has focused on several brain regions involved in the experience of depersonalization and derealization, including adaptive responses to stress via defense cascades comprising autonomic functioning, the hypothalamic-pituitary-adrenal (HPA) axis, and various other neurocircuits. Recent evidence has also demonstrated the role of more complex mechanisms that are bolstered by dissociative features, such as emotional dysregulation and disintegration of the body schema. This review intends to abridge the prevailing knowledge regarding structural and functional brain alterations associated with DPDR with that of its heterogenic manifestations. DPDR is not merely the disruption of various sensory integrations, but also of several large-scale brain networks. Although a comprehensive antidote is not available for DPDR, a holistic route to the neurobiological context in DPDR may improve general understanding of the disorder and help afflicted individuals re-establish their sense of personal identity. Such information may also be useful in the development of novel pharmacological agents and targeted psychological interventions.