Role of Ketamine in the Treatment of Psychiatric Disorders.

PURPOSE OF REVIEW: This is a comprehensive review of the literature regarding the use of ketamine as a treatment for treatment-resistant depression (TRD). It covers the epidemiology, risk factors, pathophysiology, and current treatment modalities regarding Major Depressive Disorder (MDD) and TRD. It provides background on the mechanism of action of ketamine, its history, current approved and off-label indications in the field of psychiatry, and then provides an overview of the existing evidence for the use of ketamine in the treatment of TRD. RECENT FINDINGS: MDD is a mental illness that puts an enormous strain on the affected and a high socio-economic burden on society. The illness is complex and combines genetic, pathophysiologic, and environmental factors that combine to negatively affect neurotransmitter balance in the brain. Additional evidence suggests dysregulation of the hypothalamic-pituitary (HPA) axis, brain-derived neurotrophic factor (BDNF), vitamin D levels, and involvement of pro-inflammatory markers. Core symptoms include depressed mood or anhedonia, combined with neurovegetative symptoms such as sleep impairment, changes in appetite, feelings of worthlessness and guilt, and psychomotor retardation. Current first-line treatment options are antidepressants of the selective serotonin reuptake inhibitor (SSRI) and serotonin-norepinephrine reuptake inhibitor (SNRI) class. Failure to respond to two adequate trials of treatment meets the criteria for TRD. Esketamine (Spravato) is an NMDA-receptor antagonist with additional AMPA-receptor agonist properties, which the FDA approved in 2019 to treat adult TRD in conjunction with an oral antidepressant. It can be administered intranasally, providing a rapid response and proven effective and safe. Additional research suggests that oral ketamine might be effective for PTSD and anxiety disorders. Intravenous administration of ketamine has also shown benefits for acute suicidal ideation and depression and substance use to reduce relapse rates. SUMMARY: TRD is associated with huge costs on individual and societal levels. Underlying disease processes are multifactorial and not well understood. Adjunctive therapies for TRD with proven benefits exist, but acutely depressed and suicidal patients often require prolonged inpatient stabilization. Intranasal esketamine is a new FDA-approved alternative with rapid benefit for TRD, which has also shown a rapid reduction in suicidal ideation while maintaining a favorable side-effect profile. Additional potential off-label uses for ketamine in psychiatric disorders have been studied, including PTSD, anxiety disorders, bipolar depression, and substance use disorders.

Asenapine Transdermal Patch for the Management of Schizophrenia.

Purpose of Review: This is a comprehensive review of the literature regarding the use of asenapine for the treatment of schizophrenia (SZ) in adults. It covers an introduction, epidemiology, risk factors, pathophysiology, and current treatment modalities regarding SZ, provides a background on the mechanism of action of asenapine, and then reviews the existing evidence for use of asenapine in both its sublingual and transdermal formulation in the treatment of SZ. Recent Findings: SZ is a complex and multifactorial mental disorder which is thought to combine several genetic, epigenetic, and environmental factors causing abnormalities in the dopaminergic system. Symptoms are categorized in delusions, hallucinations, disorganization, and negative presentations like affective flattening and apathy. Current treatment focuses on antipsychotic medications by means of oral administration or long-acting injection. Asenapine is a second-generation antipsychotic with 5HT-2A antagonist and 5HT-1A/1B partial agonist properties, which provides a favorable profile in targeting schizophrenic symptoms, while reducing motor side effects and improving mood and cognition. Asenapine in its sublingual formulation was FDA approved for treatment of SZ and bipolar I disorder in adults in August of 2009 and has been proven to be both effective and safe. Transdermal patch of asenapine (Secuado) was FDA approved in October of 2019, the first and only FDA approved patch for SZ in adults, which offers another strategy for treatment to improve compliance and ease of administration. Summary: SZ is a chronic and debilitating disease which is still not well understood and comes at great cost with regards to the quality of life for patients. Medication side-effects and compliance are enormous issues which take a toll on health care systems in industrialized nations and keep patients from achieving stability with their disease. Transdermal asenapine is a new first-in-class dosage form and provides a novel modality of administration. It has been shown to be effective in reducing positive, as well as negative symptoms, while still maintaining a favorable side-effect profile.

General medicine consultant of the week model shortens hospital length of stay and improves the patient journey.

BACKGROUND AND AIMS: The consultant of the week (COW) model of inpatient care means the consultants' primary focus is to deliver ward-based care daily. At Sandwell and West Birmingham Hospitals NHS Trust, a COW model has been successfully used for cardiology and stroke services. This has improved continuity of care and developed a 7-day working week. Our aim was to extend this model to all general medical consultants who manage inpatients. METHODS: We introduced the COW model to the unselected general medical take. Restructuring of consultant job plans allowed daily ward presence, 5 days per week. Outcome measures included length of stay (LOS) and accuracy of expected date of discharge (EDD). RESULTS: LOS over a 12-month period improved from an average of 9.17 days to 6.61 days. The number of EDD changes reduced, from a previous average of 3.0 changes to 1.8 changes. Consultant feedback showed there was an improvement in collaboration between teams, improved training of junior doctors and higher job satisfaction. CONCLUSIONS: Improved 5-day consultant presence is associated with reduced LOS. Learning points included the delay in implementation due to the complexity of consultant job planning. We plan to extend COW to 7-days for all general medical wards.

Gene expression profiles at different stages of collagen-induced arthritis.

The molecular basis to autoimmune arthritis is unclear. To identify candidate molecules that may be involved in the development and progression of collagen-induced arthritis (CIA), an animal model for human rheumatoid arthritis, we used microarray and real-time PCR assays to examine the gene expression profiles at the onset, peak and decline phase of CIA. Our results showed that, of the 514 immune-related genes assayed in microarrays, fifty-eight genes showed differential expression with thirty-one up-regulated and twenty-seven down-regulated in CIA joints, in comparison to normal joint tissue. By real-time PCR, expression of some chemokines/chemokine receptors, such as CCR1, CXCR4, CXCL13 and MCP1, showed significantly elevated in the inflamed joints. Quite a few genes were significantly up- or down-regulated at the peak time point, which indicates their roles in the progression of the disease. In addition, the expression levels of some genes remained significantly elevated at all stages of the disease. These gene expression profiles may help understand the pathogenesis of the disease.

Bedside placement of nasojejunal tubes: a randomised-controlled trial of spiral- vs straight-ended tubes.

BACKGROUND AND AIMS: The success rate of unguided nasojejunal feeding tube insertion is low, thus often requiring endoscopic or radiological assistance. The spiral end of the Bengmark nasojejunal tube is supposed to aid post-pyloric placement, but no comparative trial has been performed. METHODS: Patients requiring nasojejunal feeding were randomised to have either Medicina (straight) or Bengmark (spiral) nasojejunal tube placed after stratification into those with normal gastric emptying or clinical evidence of delayed gastric emptying. Nasojejunal tubes were placed at the bedside in a standard fashion without radiological guidance by the same person for pre- and/or post-operative feeding. Bolus intravenous metaclopromide (10mg) was given prior to insertion in the abnormal gastric emptying group. Abdominal radiographs were obtained at 4 and 24h, and the primary end-point was jejunal placement at 24h. RESULTS: Forty-seven patients were randomised of which 17 (11 straight, 6 spiral) could not tolerate the nasojejunal tube. Of the 30 remaining patients, 16 had normal gastric emptying. In patients with normal gastric emptying, successful placement at 24h was achieved in 78% (spiral tube), vs 14% (straight tube) (P=0.041). In the abnormal gastric emptying group, success rates were 57% and 0%, respectively (P=0.07). CONCLUSION: Spiral nasojejunal tubes are preferable to straight tubes for bedside unguided post-pyloric feeding in patients with normal gastric emptying.