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BMJ Neurology Open 2024Migraine is the second most common prevalent disorder worldwide and is a top cause of disability with a substantial economic burden. Many preventive migraine medications...
BACKGROUND
Migraine is the second most common prevalent disorder worldwide and is a top cause of disability with a substantial economic burden. Many preventive migraine medications have notable side effects that affect different body organs.
METHOD
We systematically searched for published randomised controlled trials (RCTs) using terms for migraine/headache and preventive medications. Using eligibility criteria, two reviewers independently assessed the articles. Cochrane risk-of-bias tool was applied to assess the quality of the studies. Data were classified by system organ class (SOC).
RESULTS
Thirty-two RCTs with 21 780 participants met the eligibility criteria for the incidence of adverse events (AEs). Additionally, 33 RCTs with 22 615 participants were included to synthesise the incidence of serious AEs (SAEs). The percentage of attributed AEs and SAEs to each SOC for 10 preventive drugs with different dosing regimens was calculated. Amitriptyline and topiramate had a higher incidence of nervous system disorders; Topiramate was also associated with a higher incidence of psychiatric disorders. All drugs showed a certain incidence of infections and infestations, with Onabotulinumtoxin A (BTA) having the lowest rate. BTA had a higher incidence of musculoskeletal disorders than the other drugs. Calcitonin gene-related peptide (CGRP) monoclonal antibodies (MAbs) such as fremanezumab and galcanezumab were linked to more general disorders and administration site conditions than other drugs.
CONCLUSION
Notably, the observed harm to SOCs varies among these preventive drugs. We suggest conducting head-to-head RCTs to evaluate the safety profile of oral medications, BTA, and CGRP MAbs in episodic and/or chronic migraine populations.
PROSPERO REGISTRATION NUMBER
CRD42021265993.
PubMed: 38646505
DOI: 10.1136/bmjno-2023-000616 -
Neuropsychopharmacology : Official... Feb 2024Prototypic antidepressants, such as tricyclic/tetracyclic antidepressants (TCAs), have multiple pharmacological properties and have been considered to be more effective...
Prototypic antidepressants, such as tricyclic/tetracyclic antidepressants (TCAs), have multiple pharmacological properties and have been considered to be more effective than newer antidepressants, such as selective serotonin reuptake inhibitors, in treating severe depression. However, the clinical contribution of non-monoaminergic effects of TCAs remains elusive. In this study, we discovered that amitriptyline, a typical TCA, directly binds to the lysophosphatidic acid receptor 1 (LPAR1), a G protein-coupled receptor, and activates downstream G protein signaling, while exerting a little effect on β-arrestin recruitment. This suggests that amitriptyline acts as a G protein-biased agonist of LPAR1. This biased agonism was specific to TCAs and was not observed with other antidepressants. LPAR1 was found to be involved in the behavioral effects of amitriptyline. Notably, long-term infusion of mouse hippocampus with the potent G protein-biased LPAR agonist OMPT, but not the non-biased agonist LPA, induced antidepressant-like behavior, indicating that G protein-biased agonism might be necessary for the antidepressant-like effects. Furthermore, RNA-seq analysis revealed that LPA and OMPT have opposite patterns of gene expression changes in the hippocampus. Pathway analysis indicated that long-term treatment with OMPT activated LPAR1 downstream signaling (Rho and MAPK), whereas LPA suppressed LPAR1 signaling. Our findings provide insights into the mechanisms underlying the non-monoaminergic antidepressant effects of TCAs and identify the G protein-biased agonism of LPAR1 as a promising target for the development of novel antidepressants.
Topics: Mice; Animals; Amitriptyline; Depression; Antidepressive Agents; Antidepressive Agents, Tricyclic; GTP-Binding Proteins
PubMed: 37673966
DOI: 10.1038/s41386-023-01727-9 -
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 -
Environmental Monitoring and Assessment Mar 2024Defining the environmental occurrence and distribution of chemicals of emerging concern (CECs), including pharmaceuticals and personal care products (PPCPs) in coastal...
Defining the environmental occurrence and distribution of chemicals of emerging concern (CECs), including pharmaceuticals and personal care products (PPCPs) in coastal aquatic systems, is often difficult and complex. In this study, 70 compounds representing several classes of pharmaceuticals, including antibiotics, anti-inflammatories, insect repellant, antibacterial, antidepressants, chemotherapy drugs, and X-ray contrast media compounds, were found in dreissenid mussel (zebra/quagga; Dreissena spp.) tissue samples. Overall concentration and detection frequencies varied significantly among sampling locations, site land-use categories, and sites sampled proximate and downstream of point source discharge. Verapamil, triclocarban, etoposide, citalopram, diphenhydramine, sertraline, amitriptyline, and DEET (N,N-diethyl-meta-toluamide) comprised the most ubiquitous PPCPs (> 50%) detected in dreissenid mussels. Among those compounds quantified in mussel tissue, sertraline, metformin, methylprednisolone, hydrocortisone, 1,7-dimethylxanthine, theophylline, zidovudine, prednisone, clonidine, 2-hydroxy-ibuprofen, iopamidol, and melphalan were detected at concentrations up to 475 ng/g (wet weight). Antihypertensives, antibiotics, and antidepressants accounted for the majority of the compounds quantified in mussel tissue. The results showed that PPCPs quantified in dreissenid mussels are occurring as complex mixtures, with 4 to 28 compounds detected at one or more sampling locations. The magnitude and composition of PPCPs detected were highest for sites not influenced by either WWTP or CSO discharge (i.e., non-WWTPs), strongly supporting non-point sources as important drivers and pathways for PPCPs detected in this study. As these compounds are detected at inshore and offshore locations, the findings of this study indicate that their persistence and potential risks are largely unknown, thus warranting further assessment and prioritization of these emerging contaminants in the Great Lakes Basin.
Topics: Animals; Sertraline; Lakes; Environmental Monitoring; Bivalvia; Anti-Bacterial Agents; Etoposide; Cosmetics; Antidepressive Agents; Pharmaceutical Preparations
PubMed: 38438687
DOI: 10.1007/s10661-023-12119-3 -
The Journal of Headache and Pain Apr 2024Acupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
Acupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis.
METHODS
We searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach.
RESULTS
A total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23).
CONCLUSION
Acupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence.
Topics: Humans; Tension-Type Headache; Antidepressive Agents, Tricyclic; Acupuncture Therapy; Randomized Controlled Trials as Topic
PubMed: 38679721
DOI: 10.1186/s10194-024-01776-5 -
Langmuir : the ACS Journal of Surfaces... Aug 2023We have observed ultrasmall unilamellar vesicles, with diameters of less than 20 nm, in mixtures of the tricyclic antidepressant drug amitriptyline hydrochloride (AMT)...
We have observed ultrasmall unilamellar vesicles, with diameters of less than 20 nm, in mixtures of the tricyclic antidepressant drug amitriptyline hydrochloride (AMT) and the unsaturated zwitterionic phospholipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) in physiological saline solution. The size and shape of spontaneously formed self-assembled aggregates have been characterized using complementary techniques, i.e., small-angle neutron and X-ray scattering (SANS and SAXS) and cryo-transmission electron microscopy (cryo-TEM). We observe rodlike mixed micelles in more concentrated samples that grow considerably in length upon dilution, and a transition from micelles to vesicles is observed as the concentration approaches the critical micelle concentration of AMT. Unlike the micelles, the spontaneously formed vesicles decrease in size with each step of dilution, and ultrasmall unilamellar vesicles, with diameters as small as about 15 nm, were observed at the lowest concentrations. The spontaneously formed ultrasmall unilamellar vesicles maintain their size for as long we have investigated them (i.e., several months). To the best of our knowledge, such small vesicles have never before been reported to form spontaneously in a biocompatible phospholipid-based system. Most interestingly, the size of the vesicles was observed to be strongly dependent on the chemical structure of the phospholipid, and in mixtures of AMT and the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), the vesicles were observed to be considerably larger in size. The self-assembly behavior in the phospholipid-drug surfactant system in many ways resembles the formation of equilibrium micelles and vesicles in mixed anionic/cationic surfactant systems.
Topics: Phospholipids; Unilamellar Liposomes; Micelles; Scattering, Small Angle; X-Ray Diffraction; Surface-Active Agents
PubMed: 37530182
DOI: 10.1021/acs.langmuir.3c01023 -
Cureus Feb 2024Migraine is a globally prevalent neurological disorder. Amitriptyline, a tricyclic antidepressant, has shown potential as a prophylactic treatment for migraine; however,...
Migraine is a globally prevalent neurological disorder. Amitriptyline, a tricyclic antidepressant, has shown potential as a prophylactic treatment for migraine; however, its role as a first-line medication has been debated. A modified Delphi method was used to develop consensus statements on migraine and its management. The literature review identified knowledge gaps, and two survey rounds were conducted among a panel of experts. Consensus was reached for 12 out of 23 initial survey questions, whereas no consensus was reached for four questions after the deliberation in the second round. The results showed that migraine is highly prevalent among women aged 15-35 years in India. Amitriptyline is an effective monotherapy for prophylactic migraine management, with a recommended initial dose of 5-10 mg. A gradual titration over six months achieves optimal results. Amitriptyline is also safe for managing catamenial migraine and can be used at lower doses during pregnancy to alleviate symptoms. The outcomes of this study emphasize that amitriptyline should be considered as a primary prophylactic treatment for migraine because of its efficacy and safety. The evidence-based consensus achieved is intended to serve as guidance for healthcare practitioners in India, and it is anticipated that such adoption will lead to improvement in patient outcomes and an enhancement in the quality of life for those affected by migraines.
PubMed: 38500929
DOI: 10.7759/cureus.54270 -
Cureus Oct 2023Cholesterol embolization syndrome (CES) is a rare but systemic severe disease caused by the distal showering of cholesterol crystals after angiography, major surgery,...
Cholesterol embolization syndrome (CES) is a rare but systemic severe disease caused by the distal showering of cholesterol crystals after angiography, major surgery, thrombolysis, or anticoagulation. Here, we present a case of a 74-year-old male with a history of coronary artery disease, chronic kidney disease, peripheral vascular disease, antiphospholipid syndrome, and right internal carotid artery occlusion who developed purple discoloration and ulceration involving several toes two months after coronary artery bypass surgery. A broad differential diagnosis for blue toes was considered, and a biopsy was obtained, which revealed an arterial lumen filled with large cholesterol crystal spaces, confirming the diagnosis of CES. Treatment of CES remains a bimodal approach of supportive and prophylactic care. Although there is no direct evidence in favor of antiplatelet agents, their use seems reasonable because they have been shown to reduce the risk of other cardiovascular events in patients with extensive atherosclerosis. In this case, the patient's toe pain improved with the use of topical amitriptyline ketamine and has achieved complete resolution of pain and skin discoloration at a seven-month follow-up.
PubMed: 38022197
DOI: 10.7759/cureus.46986 -
Talanta Jun 2024This article describes the synthesis of sorptive phases for bioanalysis based on the modification of cellulose paper with natural beeswax as sorbent, resulting in a...
This article describes the synthesis of sorptive phases for bioanalysis based on the modification of cellulose paper with natural beeswax as sorbent, resulting in a substrate completely renewable and sustainable. The preparation of the sorptive phases consisted of the dissolution of beeswax in hexane, followed by its drop-casting on cellulose paper and subsequent evaporation of the solvent. The beeswax modification of paper renders it hydrophobic, enabling the extraction of the target analytes, i.e., imipramine, desipramine, amitriptyline and trimipramine, via hydrophobic interactions. The main variables affecting the extraction performance were investigated (e.g., pH, ionic strength, extraction time, eluent composition, agitation speed). The analytical workflow combines a straightforward sampling, simultaneous extraction of 30 samples in 1 h, and the rapid (<2 min) determination of the analytes via direct infusion mass spectrometry. The method provided limits of detection in the range 2.0 and 3.2 μg L, and the precision, expressed as relative standard deviation, was better than 5.4 % and 8.5 % for intra and inter-day analyses, respectively. The accuracy, in terms of relative recovery, ranged from 90 % to 121 % using saliva as model biofluid.
Topics: Antidepressive Agents, Tricyclic; Cellulose; Amitriptyline; Waxes
PubMed: 38479029
DOI: 10.1016/j.talanta.2024.125860 -
Heliyon Mar 2024Both peripheral neuropathy and depression can be viewed as neurodegeneration's consequences of diabetes, at least in part coexisting with or resulting from...
Both peripheral neuropathy and depression can be viewed as neurodegeneration's consequences of diabetes, at least in part coexisting with or resulting from sodium-calcium dysbalance. This study aims to assess the therapeutic potential of the orally applied reverse-mode inhibitor of the sodium-calcium exchanger (NCX) KB-R7943 in the streptozotocin (STZ) diabetes model in rats. A pilot pharmacokinetic (PK) study with high-performance liquid chromatography with high-resolution tandem mass spectrometric detection revealed higher drug exposure (AUC), lower volume of distribution (Vd) and clearance (Cl), and faster decline of the plasma concentration (ƛ) in rats with diabetes vs. controls. Brain and heart accumulation and urinary excretion of the unmetabolized KB-R7943 at least 24 h were also demonstrated in all rats. However, heart and hippocampus KB-R7943 penetration (AUC/AUC) was higher in controls vs. diabetic rats. The development of thermal, mechanical, and chemical-induced allodynia was assessed with the Cold plate test (CPT), Randall-Stiletto (R-S) test, and 0.5% formalin test (FT). Amitriptyline 10 mg/kg, KB-R7943 5 mg/kg, or 10 mg/kg p.o once daily was applied from the 28th to the 49th day. The body weight, coat status, CPT, R-S, and FT were evaluated on days (-5), 0, and 42. On day 41, a forced swim test and 24-h spontaneous physical activities were assessed. The chronic treatment effects were calculated as % of the maximum. A dose-depended amelioration of neuropathic and depression-like effects was demonstrated. The oral application of KB-R7943 for potentially treating neurodegenerative consequences of diabetes merits further studies. The brain, heart, and kidneys are essential contributors to the PKs of this drug, and their safety involvement needs to be further characterized.
PubMed: 38524546
DOI: 10.1016/j.heliyon.2024.e27367