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Pharmaceuticals (Basel, Switzerland) Jul 2023Amitriptyline was first introduced as a medication to treat depression. Over time, this substance has been used to treat other conditions, such as gastrointestinal...
Amitriptyline was first introduced as a medication to treat depression. Over time, this substance has been used to treat other conditions, such as gastrointestinal disorders, fibromyalgia, neuropathic pain, and analgesia, among others. However, there are no published studies that provide a broad view of the possible motivations that have led to changes in the use of amitriptyline. In this study, we have identified the landscape of use for amitriptyline based on knowledge mapping of the 100 most-cited articles about this drug. We searched Web of Science Core Collection without time and language restrictions. We obtained 14,446 results, but we only used the 100 most-cited articles that had amitriptyline as the object of study. We collected the following information from each article: authors, country of the corresponding authors, year of publication, citation count, citation density (number of citations per year), and keywords. In addition, we seek to map in the chosen articles study design and research findings. We found that since 1980, the use of amitriptyline has expanded beyond depression, moving to off-label use to treat a variety of diseases and conditions, including post-herpetic neuralgia, neuropathic pain, primary fibrosis, fibromyalgia, and migraine, can be considered a drug with more clinical applicability than its original clinical indication.
PubMed: 37513958
DOI: 10.3390/ph16071047 -
Frontiers in Psychiatry 2023Depression is widespread global problem that not only severely impacts individuals' physical and mental health but also imposes a heavy disease burden on nations and...
BACKGROUND
Depression is widespread global problem that not only severely impacts individuals' physical and mental health but also imposes a heavy disease burden on nations and societies. The role of inflammation in the pathogenesis and pathophysiology of depression has received much attention, but the precise relationship between the two remains unclear. This study aims to investigate the correlation between depression and inflammation using a network medicine approach.
METHODS
We utilized a degree-preserving approach to identify the large connected component (LCC) of all depression-related proteins in the human interactome. The LCC was deemed as the disease module for depression. To measure the association between depression and other diseases, we calculated the overlap between these disease protein modules using the Sab algorithm. A smaller Sab value indicates a stronger association between diseases. Building on the results of this analysis, we further explored the correlation between inflammation and depression by conducting enrichment and pathway analyses of critical targets. Finally, we used a network proximity approach to calculate drug-disease proximity to predict the efficacy of drugs for the treatment of depression. We calculated and ranked the distances between depression disease modules and 6,100 drugs. The top-ranked drugs were selected to explore their potential for treating depression based on the hypothesis that their antidepressant effects are related to reducing inflammation.
RESULTS
In the human interactome, all depression-related proteins are clustered into a large connected component (LCC) consisting of 202 proteins and multiple small subgraphs. This indicates that depression-related proteins tend to form clusters within the same network. We used the 202 LCC proteins as the key disease module for depression. Next, we investigated the potential relationships between depression and 299 other diseases. Our analysis identified over 18 diseases that exhibited significant overlap with the depression module. Where S = -0.075 for the vascular disease and depressive disorders module, S = -0.070 for the gastrointestinal disease and depressive disorders module, and S = -0.062 for the endocrine system disease and depressive disorders module. The distance between them S < 0 implies that the pathogenesis of depression is likely to be related to the pathogenesis of its co-morbidities of depression and that potential therapeutic approaches may be derived from the disease treatment libraries of these co-morbidities. Further, considering that the inflammation is ubiquitous in some disease, we calculate the overlap between the collected inflammation module (236 proteins) and the depression module (202 proteins), finding that they are closely related (S = -0.358) in the human protein interaction network. After enrichment and pathway analysis of key genes, we identified the HIF-1 signaling pathway, PI3K-Akt signaling pathway, Th17 cell differentiation, hepatitis B, and inflammatory bowel disease as key to the inflammatory response in depression. Finally, we calculated the -score to determine the proximity of 6,100 drugs to the depression disease module. Among the top three drugs identified by drug-disease proximity analysis were Perphenazine, Clomipramine, and Amitriptyline, all of which had a greater number of targets in the network associated with the depression disease module. Notably, these drugs have been shown to exert both anti-inflammatory and antidepressant effects, suggesting that they may modulate depression through an anti-inflammatory mechanism. These findings demonstrate a correlation between depression and inflammation at the network medicine level, which has important implications for future elucidation of the etiology of depression and improved treatment outcomes.
CONCLUSION
Neuroimmune signaling pathways play an important role in the pathogenesis of depression, and many classes of antidepressants exhibiting anti-inflammatory properties. The pathogenesis of depression is closely related to inflammation.
PubMed: 37492068
DOI: 10.3389/fpsyt.2023.1184188 -
Journal of Environmental Management Oct 2023Three-dimensional heteroatom-doped graphene presents a state-of-the-art approach for effective remediation of pharmaceutical wastewater on account of its distinguished...
Three-dimensional heteroatom-doped graphene presents a state-of-the-art approach for effective remediation of pharmaceutical wastewater on account of its distinguished adsorption and physicochemical attributes. Amitriptyline is an emerging tricyclic antidepressant pollutant posing severe risks to living habitats through water supply and food chain. With ultra-large surface area and plentiful chemical functional groups, graphene oxide is a favorable adsorbent for decontaminating polluted water. Herein, a new boron-doped graphene oxide composite reinforced with carboxymethyl cellulose was successfully developed via solution-based synthesis. Characterization study revealed that the adsorbent was formed by graphene sheets intertwined into a porous network and engrafted with 13.37 at% of boron. The adsorbent has a zero charge at pH 6 and contained various chemical functional groups favoring the attachment of amitriptyline. It was also found that a mere 10 mg of adsorbent was able to achieve relatively high amitriptyline removal (89.31%) at 50 ppm solution concentration and 30 °C. The amitriptyline adsorption attained equilibrium within 60 min across solution concentrations ranging from 10 to 300 ppm. The kinetic and equilibrium of amitriptyline adsorption were well correlated to the pseudo-second-order and Langmuir models, respectively, portraying the highest Langmuir adsorption capacity of 737.4 mg/g. Notably, the predominant mechanism was chemisorption assisted by physisorption that contributed to the outstanding removal of amitriptyline. The saturated adsorbent was sufficiently regenerated using ethanol eluent. The results highlighted the impressive performance of the as-synthesized boron-doped adsorbent in treating amitriptyline-containing waste effluent.
Topics: Graphite; Amitriptyline; Boron; Adsorption; Pharmaceutical Preparations; Kinetics; Water Pollutants, Chemical; Hydrogen-Ion Concentration
PubMed: 37413724
DOI: 10.1016/j.jenvman.2023.118363 -
Cureus May 2023Chronic respiratory insufficiency can result from respiratory infections like pneumonia, which can permanently harm the lungs and respiratory system. A 21-year-old...
Chronic respiratory insufficiency can result from respiratory infections like pneumonia, which can permanently harm the lungs and respiratory system. A 21-year-old female patient arrived at our emergency medicine department (ED) complaining of acute lower-limb pain that worsened when she walked. She also reported feeling weak and having an acute, undiagnosed fever that was resolved by taking medicine two days after the day of admission. She was found to have a body temperature of 99.4°F, decreased air entry on the left side of the chest, and diminished bilateral plantar responsiveness. With the exception of a low calcium level and an increased liver function test, her biochemical indicators were normal. The left lung's basal region had fibrosis, and the right lung's hyperplasia served as a compensatory mechanism, according to the chest radiograph and CT scan of the thorax. The patient underwent treatment with intravenous pantoprazole, ondansetron, ceftriaxone, multivitamin supplementation, gabapentin, and tablets of amitriptyline. On Day 7, her lower limb pain had significantly recovered. After an eight-day hospital stay, she was discharged with instructions to follow up with the pulmonary medicine outpatient department (OPD) and the neurology OPD. A well-known occurrence known as compensatory hyperinflation of the lung happens when one lung is severely injured or rendered inoperable, leading the other lung to enlarge to make up for the loss of respiratory function. This case demonstrates the ability of the respiratory system to compensate for significant damage to one of the lungs.
PubMed: 37398719
DOI: 10.7759/cureus.39771 -
World Journal of Psychiatry Jun 2023Available pharmacotherapies for autism spectrum disorders (ASD) are reviewed based on clinical and research experience, highlighting some older drugs with emerging... (Review)
Review
Available pharmacotherapies for autism spectrum disorders (ASD) are reviewed based on clinical and research experience, highlighting some older drugs with emerging evidence. Several medications show efficacy in ASD, though controlled studies in ASD are largely lacking. Only risperidone and aripiprazole have Federal Drug Administration approval in the United States. Methylphenidate (MPH) studies showed lower efficacy and tolerability for attention deficit hyperactivity disorder (ADHD) than in the typically developing (TD) population; atomoxetine demonstrated lower efficacy but comparable tolerability to TD outcomes. Guanfacine improved hyperactivity in ASD comparably to TD. Dex-troamphetamine promises greater efficacy than MPH in ASD. ADHD medications reduce impulsive aggression in youth, and may also be key for this in adults. Controlled trials of the selective serotonin reuptake inhibitors citalopram and fluoxetine demonstrated poor tolerability and lack of efficacy for repetitive behaviors. Trials of antiseizure medications in ASD remain inconclusive, however clinical trials may be warranted in severely disabled individuals showing bizarre behaviors. No identified drugs treat ASD core symptoms; oxytocin lacked efficacy. Amitriptyline and loxapine however, show promise. Loxapine at 5-10 mg daily resembled an atypical antipsychotic in positron emission tomography studies, but may be weight-sparing. Amitriptyline at approximately 1 mg/ kg/day used cautiously, shows efficacy for sleep, anxiety, impulsivity and ADHD, repetitive behaviors, and enuresis. Both drugs have promising neurotrophic properties.
PubMed: 37383284
DOI: 10.5498/wjp.v13.i6.262 -
Arquivos de Neuro-psiquiatria Jun 2023Chronic low back pain (CLBP) is a global health problem, and gabapentin and pregabalin are often used in the treatment of patients without associated radiculopathy or...
BACKGROUND
Chronic low back pain (CLBP) is a global health problem, and gabapentin and pregabalin are often used in the treatment of patients without associated radiculopathy or neuropathy. Therefore, determining their efficacy and safety is of enormous value.
OBJECTIVE
To examine the efficacy and safety of using gabapentin and pregabalin for CLBP without radiculopathy or neuropathy.
METHODS
We performed a search on the CENTRAL, MEDLINE, EMBASE, LILACS, and Web of Science data bases for clinical trials, cohorts, and case-control studies that evaluated patients with CLBP without radiculopathy or neuropathy for at least eight weeks. The data were extracted and inserted into a previously-prepared Microsoft Excel spreadsheet; the outcomes were evaluated using the Cochrane RoB 2 tool, and the quality of evidence, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
RESULTS
Of the 2,230 articles identified, only 5 were included, totaling 242 participants. In them, pregabalin was slightly less efficacious than amitriptyline, the combination of tramadol/acetaminophen, and celecoxib, and pregabalin added to celecoxib showed no benefit when compared to celecoxib alone (very low evidence for all). On the other hand, although one study with gabapentin did not support its use in a general sample of patients with low back pain, another found a reduction in the pain scale and improved mobility (moderate evidence). No serious adverse events were observed in any of the studies.
CONCLUSION
Quality information to support the use of pregabalin or gabapentin in the treatment of CLBP without radiculopathy or neuropathy is lacking, although results may suggest gabapentin as a viable option. More data is needed to fill this current gap in knowledge.
Topics: Humans; Radiculopathy; Gabapentin; Pregabalin; Low Back Pain; Celecoxib
PubMed: 37379868
DOI: 10.1055/s-0043-1764414 -
Drug Safety Aug 2023Time- and resource-demanding activities related to processing individual case safety reports (ICSRs) include manual procedures to evaluate individual causality with the...
Developing an Artificial Intelligence-Guided Signal Detection in the Food and Drug Administration Adverse Event Reporting System (FAERS): A Proof-of-Concept Study Using Galcanezumab and Simulated Data.
INTRODUCTION
Time- and resource-demanding activities related to processing individual case safety reports (ICSRs) include manual procedures to evaluate individual causality with the final goal of dismissing false-positive safety signals. Eminent experts and a representative from pharmaceutical industries and regulatory agencies have highlighted the need to automatize time- and resource-demanding procedures in signal detection and validation. However, to date there is a sparse availability of automatized tools for such purposes.
OBJECTIVES
ICSRs recorded in spontaneous reporting databases have been and continue to be the cornerstone and the most important data source in signal detection. Despite the richness of this data source, the incessantly increased amount of ICSRs recorded in spontaneous reporting databases has generated problems in signal detection and validation due to the increase in resources and time needed to process cases. This study aimed to develop a new artificial intelligence (AI)-based framework to automate resource- and time-consuming steps of signal detection and signal validation, such as (1) the selection of control groups in disproportionality analyses and (2) the identification of co-reported drugs serving as alternative causes, to look to dismiss false-positive disproportionality signals and therefore reduce the burden of case-by-case validation.
METHODS
The Summary of Product Characteristics (SmPC) and the Anatomical Therapeutic Chemical (ATC) classification system were used to automatically identify control groups within and outside the chemical subgroup of the proof-of-concept drug under investigation, galcanezumab. Machine learning, specifically conditional inference trees, has been used to identify alternative causes in disproportionality signals.
RESULTS
By using conditional inference trees, the framework was able to dismiss 20.00% of erenumab, 14.29% of topiramate, and 13.33% of amitriptyline disproportionality signals on the basis of purely alternative causes identified in cases. Furthermore, of the disproportionality signals that could not be dismissed purely on the basis of the alternative causes identified, we estimated a 15.32%, 25.39%, and 26.41% reduction in the number of galcanezumab cases to undergo manual validation in comparison with erenumab, topiramate, and amitriptyline, respectively.
CONCLUSION
AI could significantly ease some of the most time-consuming and labor-intensive steps of signal detection and validation. The AI-based approach showed promising results, however, future work is needed to validate the framework.
Topics: United States; Humans; Artificial Intelligence; Drug-Related Side Effects and Adverse Reactions; Adverse Drug Reaction Reporting Systems; United States Food and Drug Administration; Amitriptyline; Topiramate; Databases, Factual
PubMed: 37300636
DOI: 10.1007/s40264-023-01317-0 -
Journal of Clinical Medicine Jun 2023: Vulvodynia is defined as a chronic idiopathic vulvar pain condition. This study aimed to investigate the effect of central sensitization on the prognosis of...
: Vulvodynia is defined as a chronic idiopathic vulvar pain condition. This study aimed to investigate the effect of central sensitization on the prognosis of neuromodulator treatment for vulvodynia. A total of 105 patients with vulvodynia who underwent pelvic mapping pain exploration were included and scored according to the Convergence PP Criteria for pelvic pain and central sensitization. The patients were treated according to chronic pelvic pain guidelines, and their response to treatment was evaluated. A total of 35 out 105 patients (33%) with vulvodynia had central sensitization, which was associated with comorbidities, dyspareunia, pain with micturition, and pain with defecation. Dyspareunia and pain with defecation were independent prognostic factors for central sensitization. Patients with central sensitization experienced more pain during intercourse, urination, or defecation, had more comorbidities, and responded worse to treatment. They required more treatment, with a longer response time (over 2 months). Patients with localized vulvodynia were treated with physiotherapy and lidocaine, while patients with generalized vulvodynia were treated with neuromodulators. Amitriptyline was effective in treating patients with generalized spontaneous vulvodynia and dyspareunia. Overall, this study highlights the importance of considering central sensitization in the diagnosis and treatment of vulvodynia and the need for individualized treatment based on the patient's symptoms and underlying mechanisms. Vulvodynia patients with central sensitization had more pain during intercourse, urination, or defecation, and responded worse to treatment, requiring more time and medication.
PubMed: 37298046
DOI: 10.3390/jcm12113851