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Expert Opinion on Pharmacotherapy Jun 2024Osteoarthritis (OA) related pain has affected millions of people worldwide. However, the current pharmacological options for managing OA-related pain have not achieved a... (Review)
Review
INTRODUCTION
Osteoarthritis (OA) related pain has affected millions of people worldwide. However, the current pharmacological options for managing OA-related pain have not achieved a satisfactory effect.
AREAS COVERED
This narrative review provides an overview of the current and emerging drugs for OA-related pain. It covers the drugs' mechanism of action, safety, efficacy, and limitations. The National Library of Medicine (PubMed) database was primarily searched from 2000 to 2024.
EXPERT OPINION
Current treatment options are limited and suboptimal for OA pain management. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are the recognized and first-line treatment in the management of OA-related pain, and other drugs are inconsistent recommendations by guidelines. Emerging treatment options are promising for OA-related pain, including nerve growth factor (NGF) inhibitors, ion channel inhibitors, and calcitonin gene-related peptide (CGRP) antagonists. Besides, drugs repurposing from antidepressants and antiepileptic analgesics are shedding light on the management of OA-related pain. The management of OA-related pain is challenging as pain is heterogeneous and subjective. A more comprehensive strategy combined with non-pharmacological therapy needs to be considered, and tailored management options to individualized patients.
PubMed: 38938057
DOI: 10.1080/14656566.2024.2374464 -
The Senior Care Pharmacist Jul 2024In older inpatients, anticholinergic medications can increase the risk of complications that may increase length of stay (LOS). Cyclobenzaprine is an anticholinergic...
In older inpatients, anticholinergic medications can increase the risk of complications that may increase length of stay (LOS). Cyclobenzaprine is an anticholinergic medication associated with mental status changes, falls, and injuries in older patients. The purpose of this study is to determine whether use of a lower cyclobenzaprine dose (5 mg) compared with higher dosing (10 mg) will affect LOS, 30-day readmission rates, and need for injectable psychotropic agents in inpatients 65 years of age and older. This was a retrospective cohort analysis comparing outcomes in patients 65 years of age and older who received either a 5 mg or 10 mg cyclobenzaprine dose during their inpatient admission over a 2.5-year period. The primary outcome was hospital LOS, adjusted using multivariate linear regression. Secondary outcomes included 30-day readmission rate adjusted using logistic regression and use of injectable antipsychotics or benzodiazepines. A sub-analysis evaluated the impact of the institution's implementation of a geriatric prescribing context (GEM-CON) on cyclobenzaprine dose selection. The adjusted LOS was 32.7% longer (95% CI 25.9%-39.9%) for patients exposed to higher-dose cyclobenzaprine. Use of injectable antipsychotics or benzodiazepines was also significantly greater in the higher-dose group ( < 0.001; = 0.025). Cyclobenzaprine dose was not significantly associated with readmission on multivariate analysis (OR = 0.93, 95% CI 0.45-1.93). After GEM-CON implementation, there was a significant increase in use of the recommended lower cyclobenzaprine dose ( < 0.001). Use of lower cyclobenzaprine dosing in older inpatients is associated with reduced hospital LOS and need for injectable antipsychotics and benzodiazepines.
Topics: Humans; Aged; Retrospective Studies; Male; Female; Aged, 80 and over; Length of Stay; Patient Readmission; Amitriptyline; Dose-Response Relationship, Drug; Inpatients; Cholinergic Antagonists; Cohort Studies; Antipsychotic Agents
PubMed: 38937891
DOI: 10.4140/TCP.n.2024.249 -
BMC Pulmonary Medicine Jun 2024Pulmonary embolism (PE) is a severe and life-threatening complication of venous thromboembolism. However, there is a lack of systematic studies on differences between...
BACKGROUND
Pulmonary embolism (PE) is a severe and life-threatening complication of venous thromboembolism. However, there is a lack of systematic studies on differences between female and male PE patients. This paper aimed to compare the sex-specific differences in clinical characteristics and laboratory indicators in psychotic patients with PE.
METHODS
This retrospective study enrolled psychiatric patients with PE from June 2018 to June 2022 at Shenzhen Kangning Hospital (Shenzhen Mental Health Center). Demographic characteristics, factors associated with PE, and laboratory indices were collected to assess sex-specific differences.
RESULTS
Of the 168 patients, 87 (51.8%) were female and 81 (48.2%) were male, with a mean age of 58 years for females and 46 years for male patients. The male group had higher ratio of hyperprolactinemia, more patients using antipsychotic medications, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation than the female group (p < 0.05). Female patients were significantly older, exhibited a higher prevalence of diabetes, and had a greater number of patients taking antidepressants and hypnotics/sedatives than male patients (p < 0.05). Schizophrenia spectrum disorders were more prevalent in male patients, while female patients had a higher incidence of mood disorders (p < 0.05). Among patients aged < 45 years, the male group had higher D-dimer levels at PE onset and greater D-dimer difference (p < 0.05). Among all 112 patients aged ≥ 45 years, male patients were more likely than female patients to have respiratory tract infections, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation (p < 0.05). The multiple linear regression analysis indicated that hyperprolactinemia and the use of first-generation antipsychotics (FGAs) were associated with D-dimer levels at PE onset in male patients, while the time of PE onset and protective restraints were associated with D-dimer levels at PE onset in female patients (p < 0.05).
CONCLUSION
PE-associated clinical features differ between male and female patients. These differences may imply that the processes and mechanisms of PE onset are sex specific. Male patients are more likely to have respiratory tract infections and higher D-dimer levels at PE onset than female patients. The use of FGAs may be associated with increased D-dimer in male psychiatric patients, while protective restraints may be associated with increased D-dimer in female psychiatric patients.
Topics: Humans; Male; Female; Pulmonary Embolism; Retrospective Studies; Middle Aged; Fibrin Fibrinogen Degradation Products; Sex Factors; Adult; Aged; China; Antipsychotic Agents; Risk Factors; Mental Disorders; Hyperprolactinemia; Prevalence
PubMed: 38937698
DOI: 10.1186/s12890-024-03122-6 -
The British Journal of General Practice... Jul 2024
Topics: Humans; Primary Health Care; Prognosis; Severity of Illness Index; Depression; Antidepressive Agents; Depressive Disorder
PubMed: 38936876
DOI: 10.3399/bjgp24X738537 -
Pharmacology, Biochemistry, and Behavior Jun 2024TPN672MA, an innovative antipsychotic drug candidate currently in clinical trials, acts as a dopamine D/D receptor partial agonist, serotonin 5-HT receptor agonist, and...
TPN672MA, an innovative antipsychotic drug candidate currently in clinical trials, acts as a dopamine D/D receptor partial agonist, serotonin 5-HT receptor agonist, and serotonin 5-HT receptor antagonist. Preclinical investigations have demonstrated its potential in treating the core symptoms of schizophrenia. The present study highlights TPN672MA's significant antidepressant-like effects in classical behavioral models, such as the chronic social defeat stress paradigm. The pronounced 5-HT receptor agonism and D/D receptor partial agonism of TPN672MA likely contribute to its therapeutic effects in depression. Additionally, TPN672MA's antidepressant-like efficacy may be linked to its ability to enhance the expression levels of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein-95 (PSD95) in the hippocampus. Furthermore, TPN672MA displayed a more rapid onset of antidepressant-like action. In conclusion, TPN672MA represents a promising new drug candidate for the treatment of symptoms of schizophrenia and depression.
PubMed: 38936482
DOI: 10.1016/j.pbb.2024.173809 -
European Neuropsychopharmacology : the... Jun 2024An estimated 30 % of Major Depressive Disorder (MDD) patients exhibit resistance to conventional antidepressant treatments. Identifying reliable biomarkers of...
Multimodal brain-derived subtypes of Major depressive disorder differentiate patients for anergic symptoms, immune-inflammatory markers, history of childhood trauma and treatment-resistance.
An estimated 30 % of Major Depressive Disorder (MDD) patients exhibit resistance to conventional antidepressant treatments. Identifying reliable biomarkers of treatment-resistant depression (TRD) represents a major goal of precision psychiatry, which is hampered by the clinical and biological heterogeneity. To uncover biologically-driven subtypes of MDD, we applied an unsupervised data-driven framework to stratify 102 MDD patients on their neuroimaging signature, including extracted measures of cortical thickness, grey matter volumes, and white matter fractional anisotropy. Our novel analytical pipeline integrated different machine learning algorithms to harmonize data, perform data dimensionality reduction, and provide a stability-based relative clustering validation. The obtained clusters were characterized for immune-inflammatory peripheral biomarkers, TRD, history of childhood trauma and depressive symptoms. Our results indicated two different clusters of patients, differentiable with 67 % of accuracy: one cluster (n = 59) was associated with a higher proportion of TRD, and higher scores of energy-related depressive symptoms, history of childhood abuse and emotional neglect; this cluster showed a widespread reduction in cortical thickness (d = 0.43-1.80) and volumes (d = 0.45-1.05), along with fractional anisotropy in the fronto-occipital fasciculus, stria terminalis, and corpus callosum (d = 0.46-0.52); the second cluster (n = 43) was associated with cognitive and affective depressive symptoms, thicker cortices and wider volumes. Multivariate analyses revealed distinct brain-inflammation relationships between the two clusters, with increase in pro-inflammatory markers being associated with decreased cortical thickness and volumes. Our stratification of MDD patients based on structural neuroimaging identified clinically-relevant subgroups of MDD with specific symptomatic and immune-inflammatory profiles, which can contribute to the development of tailored personalized interventions for MDD.
PubMed: 38936143
DOI: 10.1016/j.euroneuro.2024.05.015 -
Ticks and Tick-borne Diseases Jun 2024Radicular pain is the most predominant symptom among adults with Lyme neuroborreliosis (LNB) but the duration preceding and following diagnosis remains unknown. We aimed...
BACKGROUND
Radicular pain is the most predominant symptom among adults with Lyme neuroborreliosis (LNB) but the duration preceding and following diagnosis remains unknown. We aimed to investigate whether patients with LNB have increased obtainment of analgesics before and after diagnosis and for how long.
METHODS
We performed a nationwide, population-based, matched cohort study (2009-2021). all Danish residents with LNB (positive Borrelia burgdorferi intrathecal antibody index test and cerebrospinal fluid pleocytosis) were included. To form a comparison cohort, individuals from the general population were randomly extracted and matched 10:1 to patients with LNB on age and sex. Outcomes were obtainment of simple analgesics, antiepileptics, tricyclic antidepressants, serotonin and noradrenaline reuptake inhibitors, tramadol, and other opioids. We calculated monthly and six-monthly proportions of individuals with obtainment of analgesics and absolute risk differences.
RESULTS
1,056 patients with LNB and 10,560 comparison cohort members were included. An increased proportion of patients with LNB obtained analgesics from 3 months before study inclusion, especially simple analgesics, tramadol, and other opioids. Within the 0-1-month period after study inclusion, patients with LNB most frequently obtained simple analgesics (15 %), antiepileptics (11 %), and tramadol (10 %). Thereafter, obtainment of analgesics declined within a few months. A slightly larger proportion of patients with LNB obtained antiepileptics up to 2.5 years after diagnosis.
CONCLUSIONS
Up to 3 months preceding diagnosis, LNB was preceded by increased obtainment of analgesics, which suggests diagnostic delay. Importantly, most patients with LNB did not obtain analgesics after the immediate disease course, although obtainment remained more frequent up to 2.5 years after.
PubMed: 38936014
DOI: 10.1016/j.ttbdis.2024.102371 -
International Journal of Surgery... Jun 2024Postoperative depression has a profound impact on patients' postoperative rehabilitation and overall quality of life. Preventing postoperative depression is of...
BACKGROUND
Postoperative depression has a profound impact on patients' postoperative rehabilitation and overall quality of life. Preventing postoperative depression is of significant value because conventional antidepressants have a slow onset of action. Esketamine showed prompt and sustained antidepressant efficacy. Nevertheless, the safety and effectiveness of perioperative esketamine in preventing postoperative depression are still unknown. The purpose of this meta-analysis was to assess the safety and effectiveness of perioperative intravenous esketamine in relation to its ability to prevent postoperative depression.
MATERIALS AND METHODS
Randomized controlled trials were searched in the following databases: Web of Science, Cochrane Central Registry of Controlled Trials, PubMed, and Embase. The primary outcome assessed is the postoperative depression scores. Postoperative pain ratings and adverse effects constituted secondary outcomes. Subgroup analyses were carried out on the basis of multiple variables, including the absence or presence of preoperative depression, the mode of esketamine administration, the dosage of esketamine, and the type of anesthesia.
RESULTS
A total of 16 studies encompassed 1161 patients who received esketamine intervention, whereas 1106 patients served as controls. Esketamine was efficacious in reducing postoperative depression scores when administered perioperatively, and the esketamine group maintained a lower postoperative depression score than the control group more than four weeks after surgery. Esketamine effectively alleviated postoperative pain scores without increasing the occurrence of postoperative nausea and vomiting, dizziness, drowsiness, nightmares, and dissociation.
CONCLUSION
The administration of esketamine during the perioperative has the potential to decrease postoperative depression and pain scores without increasing the incidence of adverse effects.
PubMed: 38935104
DOI: 10.1097/JS9.0000000000001870 -
Chemistry & Biodiversity Jun 2024This review focus on the terpenoids as potential therapeutic agents for depression and anxiety disorders, which naturally found in a variety of plants and exhibit a wide...
This review focus on the terpenoids as potential therapeutic agents for depression and anxiety disorders, which naturally found in a variety of plants and exhibit a wide range of biological activities. Among the terpenoids discussed in this review are α-pinene, β-caryophyllene, α-phellandrene, limonene, β-linalool, 1, 8-cineole, β-pinene, caryophyllene oxide, p-cymene, and eugenol. All of these compounds have been studied extensively regarding their pharmacological properties, such as neuroprotective effect, anti-inflammation, antibacterial, regulation of neurotransmitters and antioxidant effect. Preclinical evidence are reviewed to highlight their diverse mechanisms of action and therapeutic potential to support antidepressant and anxiolytic properties. Additionally, challenges and future directions are also discussed to emphasize therapeutic utility of terpenoids for mental health disorders. Overall, this review provides a promising role of terpenoids as novel therapeutic agents for depression and anxiety, with potential implications for the development of more effective and well-tolerated treatments in the field of psychopharmacology.
PubMed: 38934531
DOI: 10.1002/cbdv.202400788 -
Neural Regeneration Research Jun 2024In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may...
In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.
PubMed: 38934398
DOI: 10.4103/NRR.NRR-D-23-01878