Exploring Esketamine's Therapeutic Outcomes as an FDA-Designated Breakthrough for Treatment-Resistant Depression and Major Depressive Disorder With Suicidal Intent: A Narrative Review.

The expansive spectrum of major depressive disorder (MDD) continues to pose challenges for psychiatrists to treat effectively. Oral antidepressant (OAD) medications that alter monoamine neurotransmitters, mainly selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs), have been the mainstay of therapy for decades. Although these drugs have been largely beneficial, a considerable subset of patients do not respond adequately to multiple conventional therapies administered for an appropriate length of time, leading to a diagnosis of treatment-resistant depression (TRD). Ketamine, a non-monoaminergic drug, has long been known for its beneficial effects on TRD when given intravenously (IV). Between 2019 and 2020, an intranasal formulation of the S (+) enantiomer of racemic ketamine, esketamine (ESK), was granted "breakthrough designation" by the FDA and approved for the indications of TRD and MDD patients exhibiting acute suicidal intent. The objective of this narrative review was to review the academic literature and collect clinical evidence that may corroborate intranasal ESK's effectiveness for its approved indications while addressing its safety and tolerability profile, adverse effects, and impact on cognition. An overview of the drug's origins, pharmacology, and standard treatment regimen are provided. The outcomes from double-blinded randomized control trials (DB-RCTs) of ESK are outlined to demonstrate the efficacy and safety data leading to its FDA approval, along with its long-term post-market safety outcomes. Comparative trials between ESK and ketamine are then evaluated to highlight ESK's consideration as a more practical alternative to ketamine in common clinical practice. The authors further discuss currently approved and developing therapies for TRD, propose future research directions, and identify the inherent limitations of the review and further research. To conduct the research required, three digital databases (PubMed, Medline, and ClinicalTrials.gov) were queried to search for key terms, including ketamine, esketamine, treatment-resistant depression, and biomarkers, using automation tools along with selective search engine results. After streamlining the results by title and abstract and removing duplicates, a total of 37 results were chosen, of which 18 are clinical trials. A reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) score was the primary efficacy endpoint for most of these clinical trials. In conclusion, intranasal ESK, when used as an adjunct to market OADs, shows greater efficacy in treating TRD and MDD with suicidal intent compared to OADs and placebo alone and provides a more suitable alternative to IV ketamine. It is important to note that further research is required to fully understand the novel mechanism of action of ESK, as well as the establishment of a consensus definition of TRD, which may facilitate better detection and treatment protocols. More focused quantitative and qualitative ESK studies are needed, as well as those pertaining to its use in patients with co-existing mental illnesses.

Advocacy Training in Residency and Addressing Needs in Child and Adolescent Psychiatry: A 30-Year Review.

Historically providing specialized advocacy training to Child and Adolescent Psychiatrists (CAP) beyond traditional medical education has been ambiguous at best. This is alarming particularly in light of the National Emergency in Child and Adolescent Mental Health and the increasing concern about health inequities resulting from social determinants of health (SDH). While Graduate Medical Education (GME) programs are adopting advocacy curricula, the authors argue that the shortage of trained CAPs and the growing need for advocacy makes it essential to focus on advocacy training that targets patients, organizations, or entire populations. The authors performed a systematic literature review across all medical specialties, highlighting the inadequacy of current advocacy training for CAPs, particularly in comparison to pediatrics, and the Accreditation Council of Graduate Medical Education (ACGME) requirements. The article suggests that advocacy training should be more emphasized in CAP training to address health inequities and promote better outcomes for children and adolescents. The training focused on medical-legal partnerships (MLP) is particularly crucial in addressing the social causes of health disparities and addressing unmet needs such as food, housing, and income that drive disparities, especially amongst vulnerable populations. The article concludes that providing an informed and evidence-based representation of current practices and methodologies used to train residents around advocacy is essential to ensure that CAPs are prepared to advocate for their patients and address health disparities resulting from SDH. Given the growing demand for mental health services and the unprecedented need for advocacy, specialized training for CAPs can no longer be ignored.

Preserving Immunity for Reporters of Medical Child Abuse.

All American jurisdictions have laws protecting children from abuse and neglect. Mandated reporters, including health professionals, whether their suspicions ultimately are substantiated or unfounded, are entitled to immunity when their reports are entered in good faith. When harm takes the form of medical child abuse (MCA, also known as Munchausen syndrome by proxy or factitious disorder imposed on another), its origin is ambiguous, at least initially. Questions arise as to whether the caregiver intended to deceive medical professionals and if the condition improved when the child was separated from the caregiver. Clinicians may have an obligation to report MCA in difficult-to-diagnose cases or those where parents press for hospitalizations and procedures. Substantiated cases may lead to removal of children from homes and criminal prosecution of parents. This can result in backlash against the reporter by the parents, with claims of malpractice, official misconduct, intentional harm, fraud or conspiracy to commit fraud, defamation (libel or slander), or all of the above. This article examines case law regarding alleged departures from good-faith reporting of MCA and explores potential limitations to immunity provided to mandated reporters. The findings include no significant instances in which the immunity shield for good-faith reporting was pierced.

Editors' Note and Special Communication: Research Priorities in Child and Adolescent Mental Health Emerging From the COVID-19 Pandemic.

Over the last year, the coronavirus disease 2019 (COVID-19) pandemic has resulted in profound disruptions across the globe, with school closures, social isolation, job loss, illness, and death affecting the lives of children and families in myriad ways. In an Editors' Note in our June 2020 issue,1 our senior editorial team described this Journal's role in advancing knowledge in child and adolescent mental health during the pandemic and outlined areas we identified as important for science and practice in our field. Since then, the Journal has published articles on the impacts of the pandemic on child and adolescent mental health and service systems,2-5 which are available in a special collection accessible through the Journal's website.6 Alongside many opinion papers, the pace of publication of empirical research in this area is rapidly expanding, covering important issues such as increased frequency of mental health symptoms among children and adolescents3,5,7-10 and changes in patterns of clinical service use such as emergency department visits.11-14 As the Senior Editors prepared that Editors' Note, they were acutely aware that the priorities that they identified were broad and generated by only a small group of scientists and clinicians. Although this had the advantage of enabling us to get this information out to readers quickly, we decided that a more systematic approach to developing recommendations for research priorities would be of greater long-term value. We were particularly influenced by the efforts of the partnership between the UK Academy of Medical Scientists and a UK mental health research charity (MQ: Transforming Mental Health) to detail COVID-19-related research priorities for "Mental Health Science" that was published online by Holmes et al. in The Lancet Psychiatry in April 2020.15 Consistent with its focus on mental health research across the lifespan, several recommendations highlighted child development and children's mental health. However, a more detailed assessment of research priorities related to child and adolescent mental health was beyond the scope of that paper. Furthermore, the publication of that position paper preceded the death of George Floyd at the hands of Minneapolis police on May 25, 2020, which re-energized efforts to acknowledge and to address racism and healthcare disparities in the United States and many other countries. To build upon the JAACAP Editors' Note1 and the work of Holmes et al.,15 we conducted an international survey of professionals-practitioners and researchers-working on child and adolescent development and pediatric mental health to identify concerns about the impact of the pandemic on children, adolescents, and their families, as well as what is helping families navigate these impacts, and the specific research topics that are of greatest importance.