Potassium channel modulators and schizophrenia: an overview of investigational drugs.

INTRODUCTION: Schizophrenia is a severe mental illness comprising positive, negative, and cognitive symptoms. Existing pharmacologic options exert their actions on the dopamine receptor but are largely ineffective at treating negative and cognitive symptoms. Alternative pharmacologic options that do not act directly on the dopamine receptor are being investigated, including potassium channel modulators. It has been hypothesized that dysfunctional fast-spiking parvalbumin-positive GABA interneurons, regulated by Kv3.1 and Kv3.2 potassium channels, contribute to the symptoms of schizophrenia, making potassium channels an area of clinical interest. AREAS COVERED: This review will highlight potassium channel modulators for the treatment of schizophrenia, with a focus on AUT00206. Background on Kv3.1 and Kv3.2 potassium channels will be explored. Our search strategy included a literature review utilizing PubMed, Clinicaltrials.gov, and sources available on the manufacturer's website. EXPERT OPINION: Initial data on potassium channel modulators is promising; however, further study is needed, and existing evidence is limited. Early data suggests that dysfunctional GABA interneurons can be ameliorated through modulators of Kv3.1 and Kv3.2 channels. AUT00206 has been shown to improve dopaminergic dysfunction induced by ketamine and PCP, improve resting gamma power in patients with schizophrenia, impact dopamine synthesis capacity in a subgroup of individuals with schizophrenia, and affect reward anticipation-related neural activation.

Using Longitudinal Curriculum to Improve Psychiatry Residents' Attitudes Regarding Firearm Anticipatory Guidance.

OBJECTIVE: Over the last decade, there has been an increased focus on firearm use in violent acts and suicides. There is no known published firearm safety curriculum specific to psychiatric training and limited guidance on curriculum development from national organizations. The authors' goals were to develop a firearm lecture series that would encompass essential knowledge related to firearm safety and risk assessments and assess its effect on psychiatric residents' interest and confidence in firearm safety guidance. METHODS: The authors developed a six-lecture series on firearm safety that was conducted over all post-graduate year (PGY) training levels and a grand rounds on basic firearm safety. All levels of psychiatry residents at one urban academic center participated in a pre- and post-lecture series questionnaire designed to evaluate attitudes related to firearm safety guidance. They developed and administered the questionnaire through New Innovations collecting qualitative and quantitative data for analysis. The quantitative analysis was completed using paired t-test. RESULTS: Forty-seven residents participated. Twenty-seven respondents met inclusion criteria: attended at least one lecture or the grand rounds, completed pre- and post-lecture surveys, and submitted their pre-lecture survey before their first lecture. After the educational intervention, there was a statistically significant increase (p<0.05) in interest in firearm safety, and confidence in all areas surveyed-risk assessment, safety guidance, and pertinent legislation. CONCLUSIONS: The curriculum increased residents' interest and confidence in providing firearm safety guidance. Areas of development include assessing the curriculum's impact on clinical practice.

Approaching differential diagnosis and decisional capacity assessment in the context of COVID-19 conspiracy beliefs: A narrative review and clinical discussion.

OBJECTIVE: COVID-19 conspiracy theories have become widespread since the onset of the pandemic and compound the existing challenges of decisional capacity assessment. This paper aims to review the literature pertaining to decisional capacity assessment in the context of COVID-19 conspiracy beliefs and synthesize a practical approach with an emphasis on differential diagnosis and clinical pearls for the practicing physician. METHODS: We reviewed papers on decisional capacity assessment and differential diagnosis in the context of COVID-19 conspiracy beliefs. A literature search was conducted using the US National Library of Medicine's PubMed.gov resource and Google Scholar. RESULTS: The resulting article content was utilized to synthesize a practical approach to decisional capacity assessment in the context of COVID-19 conspiracy beliefs. Specifically, aspects related to the history, taxonomy, evaluation, and management are reviewed. CONCLUSIONS: Appreciating the nuanced differences between delusions, overvalued ideas, and obsessions while with integrating the non-cognitive domains of capacity into the assessment are crucial to navigating the wide differential diagnosis of COVID-19 conspiracy beliefs. It is important to attempt to clarify and optimize patient decision-making abilities by addressing circumstances, attitudes, and cognitive styles specific to patients with seemingly irrational beliefs about COVID-19.

Sexual assault in the inpatient psychiatric setting.

Sexual assault in the inpatient psychiatric setting is a significant problem with serious, lasting consequences. It is important for psychiatric providers to appreciate the nature and magnitude of this problem to be able to provide an appropriate response when faced with these challenging scenarios, as well as to advocate for the implementation of preventive measures. This article provides a review of the existing literature regarding sexual behavior in the inpatient psychiatric unit, describing the epidemiology of sexual assaults in these settings, and exploring the characteristics of both victims and perpetrators, with a particular focus on factors of relevance to the inpatient psychiatric patient population. Inappropriate sexual behavior in inpatient psychiatric settings is common, however the varying definition of such throughout the literature serves as a challenge to clearly identifying the frequency of specific behaviors. The existing literature does not identify a way to reliably predict which patients are most likely to engage in sexually inappropriate behaviors on an inpatient psychiatric unit. The medical, ethical, and legal challenges that such cases present are defined, followed by a review of current management and prevention strategies, and suggested future directions for research.

Sublingual dexmedetomidine: repurposing an anesthetic as an anti-agitation agent.

INTRODUCTION: Especially when acutely ill, individuals with schizophrenia and bipolar disorder can present with agitated behavior. The initial approach to agitation management are non-pharmacologic strategies such as verbal de-escalation techniques; however, pharmacologic interventions may be needed. Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist, and a sublingual formulation has been approved in the US for the treatment of agitation associated with schizophrenia and bipolar disorder in adults. AREAS COVERED: The authors review the published literature on sublingual dexmedetomidine using the US National Library of Medicine's PubMed.gov resource. Pharmacodynamics, pharmacokinetics, and efficacy and tolerability findings are summarized. The authors also provide a discussion to its potential place in the treatment armamentarium. EXPERT OPINION: Sublingual dexmedetomidine is an effective and well-tolerated pharmacologic option for the treatment of agitation associated with schizophrenia and bipolar disorder. The sublingual method of administration allows for a rapid onset of action with treatment effects beginning as early as 20 minutes after administration. Adverse effects include somnolence, hypotension, oral paresthesia, hypoesthesia, and dry mouth. Further study will be needed to evaluate sublingual dexmedetomidine in real-world patients receiving concomitant psychotropic medications.

Asenapine: an atypical antipsychotic with atypical formulations.

Asenapine is a second-generation (atypical) antipsychotic medication not available in a pill that can be swallowed; rather, it is commercialized in sublingual and transdermal formulations. This is a consequence of extensive first-pass metabolism if ingested. The sublingual formulation is approved in many jurisdictions for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder and is available generically. The efficacy profile is well characterized in a number of clinical trials, including an off-label use for the management of agitation. Obstacles to its use include food and drink restrictions, twice-daily dosing and adverse effects such as dysgeusia (distorted, altered, or unpleasant taste) and oral hypoesthesia (numbness). Transdermal asenapine was approved by the US Food and Drug Administration in 2019 for the treatment of schizophrenia in adults. Efficacy was established in a registrational study examining acutely ill inpatients with schizophrenia. The patch needs to changed once daily. Obstacles to its use include the potential for skin reactions such as erythema and pruritis, and being a branded product, it is more costly than other options. This is a narrative review of the chemistry and pharmacokinetics/pharmacodynamics of asenapine, as well as summarizing the efficacy and tolerability of both sublingual and transdermal asenapine, and its possible place in treatment.

A Rare Case Report of a Corpus Callosal Splenial Lesion in the Context of Atypical Neuroleptic Malignant Syndrome.

In this report, we describe a case of atypical neuroleptic malignant syndrome (NMS) presenting with an isolated lesion in the splenium of the corpus callosum (ILSCC). There is a paucity of information regarding this topic within the literature and only 7 previous case reports have been published at the time of writing. To our knowledge, this case report is also the first to describe an atypical NMS variant in the context of an ILSCC. In this report, we describe the important considerations in formulating differential diagnosis for ILSCC and are the first report to propose a possible pathophysiological mechanism relating ILSCC with NMS.