scholarly journals Urothelial toxicity of esketamine in the treatment of depression

2020 ◽  
Vol 237 (11) ◽  
pp. 3295-3302
Author(s):  
Hannelore Findeis ◽  
Cathrin Sauer ◽  
Anthony Cleare ◽  
Michael Bauer ◽  
Philipp Ritter
Keyword(s):  
Laboratory Data ◽  
Rapid Onset ◽  
Treatment Schedule ◽  
Treatment Of Depression ◽  
Icd 10 ◽  
Repeated Doses ◽  
Free Haemoglobin ◽  
Leukocyte Concentration ◽  
Depression Ratings ◽  
Antidepressant Action

Abstract Rationale Ketamine is the first widely used substance with rapid-onset antidepressant action. However, there are uncertainties regarding its potential urothelial toxicity, particularly after repeated application. In the context of rising recreational ketamine use, severe side effects affecting the human urinary tract have been reported. It is assumed that ketamine interacts with bladder urothelial cells and induces apoptosis. Objectives This study aimed to assess whether single or repeated doses of esketamine used in an antidepressant indication are associated with urinary toxicity. Methods We included male and female inpatients with a current episode of depression and a diagnosis of recurrent depressive disorder, bipolar disorder or schizoaffective disorder according to ICD-10 criteria (n = 25). The esketamine treatment schedule involved a maximum of 3× weekly dosing at 0.25–0.5 mg/kg i.v. or s.c. The primary outcome was the change in urine toxicity markers (leukocytes, erythrocytes, protein and free haemoglobin). Description of demographic, clinical and laboratory data was conducted using means, standard deviations, frequencies and percentages. Changes in urinary toxicity markers over time were evaluated using linear mixed models with gender as a covariate. Results The participants received an average of 11.4 (SD 8) esketamine treatments, and an average number of 11.2 (SD 8) urine samples were analysed over the course of treatment. Neither urinary leukocyte concentration (F(20; 3.0) = 3.1; p = 0.2) nor erythrocyte concentration (F(20;2.2) = 4.1; p = 0.2) showed a significant trend towards increase during the course of esketamine treatment. Similarly, free haemoglobin and protein concentrations, which were analysed descriptively, did not display a rise during treatment. There was a significant improvement in depression ratings after esketamine treatment (p < 0.001). Conclusions This study is, to the best of our knowledge, the first to focus on urothelial toxicity of esketamine used in antidepressant indication and dose. The results indicate that the use of single or repeated doses of esketamine is unlikely to cause urothelial toxicity. The results are in need of confirmation as sample size was small.

Neuroplasticity: A Key Player in the Antidepressant Action of Chinese Herbal Medicine

2021 ◽  
pp. 1-19
Author(s):  
Baomei Xia ◽  
Chang Chen ◽  
Weiwei Tao
Keyword(s):  
Herbal Medicine ◽  
Chinese Herbal Medicine ◽  
Antidepressant Effect ◽  
Glutamatergic System ◽  
Monoamine Neurotransmitters ◽  
Chinese Herbal ◽  
Treatment Of Depression ◽  
Neural Apoptosis ◽  
Treatment Theory ◽  
Antidepressant Action

Traditional Chinese medicine (TCM) is a systematic medicine. It provides alternative strategies for the treatment of depression with its clinical experience, comprehensive diagnosis, and treatment theory. Chinese herbal medicine (CHM) is the major form of TCM prescription, and numerous CHMs have been demonstrated to possess remarkable antidepressant-like properties. A diversity of mechanisms have been implicated in CHM-associated antidepressant property. This paper reviewed the neuroplastic mechanisms underlying the antidepressant actions of CHM, finding that CHM repairs neuroplasticity by improving neurogenesis, neurotrophic factors, synaptic spine morphology, cell signaling, glutamatergic system, monoamine neurotransmitters, and neural apoptosis. CHM thereby exerts an antidepressant effect, attempting to offer a better understanding of the mechanisms implicated in TCM-related antidepressant-like efficacy and laying a foundation for the scientific evaluation and development of TCM in treating depression.

scholarly journals Prolonged epigenetic and synaptic plasticity alterations following single exposure to a psychedelic in mice

2021 ◽  
Author(s):  
Mario de la Fuente Revenga ◽  
Bohan Zhu ◽  
Christopher A. Guevara ◽  
Lynette B. Naler ◽  
Justin M. Saunders ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Clinical Evidence ◽  
Single Exposure ◽  
Hyperactivity Disorder ◽  
Treatment Of Depression ◽  
Biological Substrates ◽  
Spine Structure ◽  
Fast Acting ◽  
Underlying Risk ◽  
Antidepressant Action

Clinical evidence suggests a potential therapeutic effect of classic psychedelics for the treatment of depression. The most outstanding and distinct characteristic is the rapid and sustained antidepressant action with one single exposure to the drug. However, the biological substrates and key mediators of psychedelics’ enduring action remain unknown. Here, we show that a single administration of the psychedelic DOI produced fast-acting effects on frontal cortex dendritic spine structure and acceleration of fear extinction via the 5-HT2A receptor. Additionally, a single dose of DOI led to changes in chromatin organization particularly at enhancer regions of genes involved in synaptic assembly that stretched for days after the psychedelic exposure. DOI-induced alterations in neuronal epigenome overlapped with genetic loci associated with schizophrenia, depression and attention deficit hyperactivity disorder. Together, these data support the notion that epigenetic-driven changes in synaptic plasticity operate as the mechanistic substrate of psychedelic’s long-lasting antidepressant action but also warn on the limitations in individuals with underlying risk for psychosis.

scholarly journals The ACE (Albumin, CRP and Endoscopy) Index in Acute Colitis: A Simple Clinical Index on Admission that Predicts Outcome in Patients With Acute Ulcerative Colitis

2020 ◽  
Author(s):  
Rebecca K Grant ◽  
Gareth-Rhys Jones ◽  
Nikolas Plevris ◽  
Ruairi W Lynch ◽  
Philip W Jenkinson ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Predictive Value ◽  
Laboratory Data ◽  
Area Under The Curve ◽  
Binary Logistic Regression ◽  
High Risk Population ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Icd 10

Abstract Background Intravenous (IV) steroids remain the first-line treatment for patients with acute ulcerative colitis (UC). However, 30% of patients do not respond to steroids, requiring second-line therapy and/or surgery. There are no existing indices that allow physicians to predict steroid nonresponse at admission. We aimed to determine if admission biochemical and endoscopic values could predict response to IV steroids. Methods All admissions for acute UC (ICD-10 K51) between November 1, 2011, and October 31, 2016 were identified. Case note review confirmed diagnosis; clinical, endoscopic, and laboratory data were collected. Steroid response was defined as discharge home with no further therapy for active UC. Nonresponse was defined as requirement for second-line therapy or surgery. Univariate and binary logistic regression analyses were employed to identify factors associated with steroid nonresponse. Results Two hundred and thirty-five acute UC admissions were identified, comprising both acute severe and acute nonsevere UC; 155 of the 235 patients (66.0%) responded to steroids. Admission C-reactive protein (CRP) (P = 0.009, odds ratio [OR] 1.006), albumin (P &lt; 0.001, OR 0.894) and endoscopic severity (P &lt; 0.001, OR 3.166) differed significantly between responders and nonresponders. A simple UC severity score (area under the curve [AUC] 0.754, P &lt; 0.001) was derived from these variables; 78.1% (25 of 32) of patients with concurrent CRP ≥50 mg/L, albumin ≤30 g/L, and increased endoscopic severity (severe on physician’s global assessment) (maximum score = 3) did not respond to IV steroids (positive predictive value [PPV] 78.1%, negative predictive value [NPV] 87.1%). Conclusions More than three quarters of patients scoring 3 (albumin ≤30 g/L, CRP ≥50 mg/L, and increased endoscopic severity) did not respond to IV steroids. This combination of parameters (ACE) identifies on admission a high-risk population who may benefit from earlier second-line medical treatment or surgical intervention.

scholarly journals Riluzole Stimulates BDNF Release from Human Platelets

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Patrick Türck ◽  
Marcos Emílio Frizzo
Keyword(s):  
Healthy Subjects ◽  
Direct Action ◽  
Human Platelets ◽  
Mechanisms Of Action ◽  
Bdnf Expression ◽  
Extracellular Glutamate ◽  
Low Concentrations ◽  
Treatment Of Depression ◽  
The Central Nervous System ◽  
Antidepressant Action

Brain-derived neurotrophic factor (BDNF) has several functions in the central nervous system, where it contributes to brain development and its functionality through affecting neuronal survival and activity and also modulating neurotransmitter levels. This neurotrophin is also found in the serum, but its origin and peripheral function remain unknown. Although the source of circulating BDNF is uncertain, it is stored in platelets and can be released through pharmacological treatment. Decreased levels of BDNF in the serum have been related to the pathophysiology of depression, and this relationship is reinforced by the reversal of this condition by treatment with antidepressants. Recently, riluzole has been proposed for the treatment of depression because it has the ability to lower extracellular glutamate levels and increase BDNF expression; and both mechanisms could be associated with its antidepressant action. Considering that riluzole enhances BDNF levels in the serum of patients, we investigated if treatment with this drug could stimulate the release of this neurotrophin from human platelets obtained from healthy subjects. When platelets were incubated with riluzole for 4 h, the basal value of BDNF (92.9±11.1 pg 10−6platelets) was significantly increased (P<0.05,n=27). This stimulatory effect was achieved at low concentrations of riluzole (from 10 µM) and was not observed when platelets were incubated with the drug for 24 h. The direct action of riluzole evoking BDNF release from human platelets at therapeutic concentrations is important and may contribute to the understanding of its mechanisms of action in the treatment of depression.

Mechanism of action of dextromethorphan/quinidine: comparison with ketamine

CNS Spectrums ◽  
2013 ◽  
Vol 18 (5) ◽  
pp. 225-227 ◽  
Author(s):  
Stephen M. Stahl
Keyword(s):  
Mood Disorders ◽  
Short Duration ◽  
Mechanism Of Action ◽  
Intravenous Administration ◽  
Rapid Onset ◽  
Treatment Resistant ◽  
Antidepressant Effects ◽  
Repeated Doses

ISSUE:Reports of rapid-onset but short-duration antidepressant effects in patients with treatment-resistant mood disorders after intravenous administration of ketamine have prompted efforts to find an agent with ketamine's properties that can be administered orally in repeated doses in order to sustain that action. One candidate for this is dextromethorphan, and here the pharmacologic mechanism of action is compared and contrasted with that of ketamine.

scholarly journals Validating a computable phenotype for nephrotic syndrome in children and adults using PCORnet® data

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0002892021
Author(s):  
Andrea L. Oliverio ◽  
Dorota Marchel ◽  
Jonathan P. Troost ◽  
Isabelle Ayoub ◽  
Salem Almaani ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Language Processing ◽  
Laboratory Data ◽  
Area Under The Curve ◽  
The United States ◽  
Primary Nephrotic Syndrome ◽  
Common Causes ◽  
Icd 10 ◽  
Positive Classification ◽  
Sensitivity Specificity

Background: Primary nephrotic syndromes are rare diseases which impedes adequate sample size for observational patient-oriented research and clinical trial enrollment. A computable phenotype may be powerful in identifying patients with these diseases for research across multiple institutions. Methods: A comprehensive algorithm of inclusion and exclusion ICD-9 and ICD-10 codes to identify patients with primary nephrotic syndrome was developed. The algorithm was executed against the PCORnet® CDM at 3 institutions from Jan 1, 2009 to Jan 1, 2018, where a random selection of 50 cases and 50 non-cases (individuals not meeting case criteria seen within the same calendar year and within five years of age of a case) were reviewed by a nephrologist, for a total of 150 cases and 150 non-cases reviewed. The classification accuracy (sensitivity, specificity, positive and negative predictive value, F1 score) of the computable phenotype was determined. Results: The algorithm identified a total of 2,708 patients with nephrotic syndrome from 4,305,092 distinct patients in the CDM at all sites from 2009-2018. For all sites, the sensitivity, specificity, and area under the curve of the algorithm were 99% (95% CI: 97-99%), 79% (95% CI: 74-85%), and 0.9 (0.84-0.97), respectively. The most common causes of false positive classification were secondary FSGS (9/39) and lupus nephritis (9/39). Conclusion: This computable phenotype had good classification in identifying both children and adults with primary nephrotic syndrome utilizing only ICD-9 and ICD-10 codes, which are available across institutions in the United States. This may facilitate future screening and enrollment for research studies and enable comparative effectiveness research. Further refinements to the algorithm including use of laboratory data or addition of natural language processing may help better distinguish primary and secondary causes of nephrotic syndrome.

scholarly journals Can AI Help Pediatricians? Diagnosing Kawasaki Disease Using DRSA

Children ◽  
2021 ◽  
Vol 8 (10) ◽  
pp. 929
Author(s):  
Bartosz Siewert ◽  
Jerzy Błaszczyński ◽  
Ewelina Gowin ◽  
Roman Słowiński ◽  
Jacek Wysocki
Keyword(s):  
Kawasaki Disease ◽  
General Condition ◽  
Early Stage ◽  
Laboratory Data ◽  
Decision Rules ◽  
Final Diagnosis ◽  
International Classification Of Diseases ◽  
Reactive Protein ◽  
Classification Of Diseases ◽  
Icd 10

The DRSA method (dominance-based rough set approach) was used to create decision-making rules based on the results of physical examination and additional laboratory tests in the differential diagnosis of Kawasaki disease (KD), infectious mononucleosis and S. pyogenes pharyngitis in children. The study was conducted retrospectively. The search was based on the ICD-10 (International Classification of Diseases) codes of final diagnosis. Demographic and laboratory data from one Polish hospital (Poznan) were collected. Traditional statistical methods and the DRSA method were applied in data analysis. The algorithm formed 45 decision rules recognizing KD. The rules with the highest sensitivity (number of false negatives equals zero) were based on the presence of conjunctivitis and CRP (C-reactive Protein) ≥ 40.1 mg/L, thrombocytosis and ESR (Erythrocyte Sedimentation Rate) ≥ 77 mm/h; fair general condition and fever ≥ 5 days and rash; fair general condition and fever ≥ 5 days and conjunctivitis; fever ≥ 5 days and rash and CRP ≥ 7.05 mg/L. The DRSA analysis may be helpful in diagnosing KD at an early stage of the disease. It can be used even with a small amount of clinical or laboratory data.

The Use of Ketamine as Therapy for Depression

2021 ◽  
Vol 1 (2) ◽  
pp. 28-31
Author(s):  
Lovina Lovina
Keyword(s):  
Chronic Pain ◽  
Clinical Practice ◽  
Side Effects ◽  
Developed Countries ◽  
Rapid Onset ◽  
Systemic Arterial Pressure ◽  
Chronic Pain Management ◽  
Extracellular Glutamate ◽  
Treatment Of Depression ◽  
New Generation

Depressive disorder is still a significant problem in several developed countries and is morbidity caused by mental disorders. With the development of science, now discovered the unique pharmacodynamic properties of ketamine, which is used as an antidepressant. As we know in clinical practice, ketamine is used for anaesthesia, analgesia, sedation, and chronic pain management. Rapid-onset antidepressants resulted from increased levels of BDNF in the hippocampus. Extracellular glutamate agents are not new for the treatment of depression. According to the neurobiology view, depression is a monoaminergic phenomenon, so this is the impetus for discovering a new generation of antidepressants. Ketamine can be given intravenously in subanesthetic doses. Still, monitoring must be carrying in therapy administration because of the possible side effects such as hypersalivation, tachycardia, increased systemic arterial pressure, and intracranial pressure.

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