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Chronic stress is a universal condition commonly associated with many psychiatric diseases. An extensive body of evidence discussed hippocampal affection upon chronic stress exposure, however, the underlying molecular pathways still need to be identified. We investigated the impact of chronic stress on miR200/BMP/Olig‐2 signaling and hippocampal myelination. We also compared the effects of chronic administration of amitriptyline and cholecalciferol on chronically stressed hippocampi. Both amitriptyline and cholecalciferol significantly decreased serum cortisol levels, reduced immobility time in the forced swim test, increased the number of crossed squares in open field test, decreased the hippocampal expression of bone morphogenetic protein 4 (BMP4) and its messenger RNA (mRNA) levels, reduced miR200 expression as compared to untreated chronically stressed rats. Also, both drugs amended the hippocampal neuronal damage, enhanced the surviving cell count, and increased the pyramidal layer thickness of Cornu Ammonis subregion 1 (CA1) and granule cell layer of the dentate gyrus. Cholecalciferol was more effective in increasing the area percentage of myelin basic protein (MBP) and Olig‐2 positive cells count in hippocampi of chronic stress‐exposed rats than amitriptyline, thus enhancing myelination. We also found a negative correlation between the expression of BMP4, its mRNA, miR200, and the immunoexpression of MBP and Olig‐2 proteins. This work underscores the amelioration of the stress‐induced behavioral changes, inhibition of miR200/BMP4 signaling, and enhancement of hippocampal myelination following chronic administration of either amitriptyline or cholecalciferol, though cholecalciferol seemed more effective in brain remyelination. [ABSTRACT FROM AUTHOR]

The development and validation of two uncomplicated, selective, and non-extraction-based visible spectrophotometric methods was carried out for the quantification of a tricyclic antidepressant amitriptyline hydrochloride as pharmaceutical tablets as well as in its pure form. The methods rely on the formation of ion pair complexes between amitriptyline base and two acidic dyes, bromothymol blue and bromocresol purple, which were subsequently measured at 410 and 400 nm, respectively. The developed methods included numerous reaction variables that were examined and improved. Beer's law is applicable under optimal conditions for the bromothymol blue and bromocresol purple methods, respectively, over concentrations from 0.5 to 12.5 μg mL−1 and from 0.5 to 10.0 μg mL−1 amitriptyline hydrochloride. The computed values of molar absorptivity were 1.79 × 104 and 2.32 × 104 L.mol−1.cm−1 for bromothymol blue and bromocresol purple methods, respectively, with Sandell's sensitivity values of 0.0155 and 0.0119 μg cm−2. Both detection limits and quantification limits were computed and determined to be 0.55 and 1.67 μg mL−1 for bromothymol blue method, and 0.49 and 1.49 μg mL−1 for bromocresol purple method, respectively. The developed methods were successfully applied to estimate the concentration of amitriptyline hydrochloride in bulk form and commercial pills. Therefore, these methods demonstrate promising potential for testing this drug in labs for quality control. Spectrophotometric quantification of amitriptyline hydrochloride in pharmaceutical tablets: method development and validation [ABSTRACT FROM AUTHOR]

Concerns related to environmental risks associated with pharmaceuticals and personal care products (PPCPs) have led researchers to seek methods for assessing and monitoring these contaminants in the aquatic environment. Identifying and validating risk assessment tools that can evaluate ecological concerns and risks associated with PPCPs is critical. Herein, the suitability of a dose-related risk and effect assessment model, which estimates predicted environmental concentrations and allowed comparisons with predicted no effect concentrations determined, in combination with in vitro analyses of the whole effluent toxicity, was verified for the characterization of a PPCP hazard. Concentrations of the most utilized PPCPs in Norway were measured in influent and effluent samples and used to parameterize the fate model. Greater than 90% removal was attained for 12 out of 22 detected PPCPs. Removal was not dependent on the class or the concentration of the specific substance and varied between 12% and 100%. The PPCPs detected in the discharged wastewater were utilized to assess individual contributions to the risk of the effluent, and no risk was identified for the targeted 30 PPCP. The simulations provided valuable information regarding the discharge plume distribution over time, which can aid planning of future environmental monitoring investigations. Bioassays (using fish liver cells, PLHC-1) were used for assessing overall effluent toxicity, through cell viability, production of reactive oxygen species, and ethoxyresorufin-O-deethylase (EROD) activities. The present study may allow regulators to use risk-based strategies over removal criteria for monitoring studies and confirms the importance to take PPCP contamination into consideration when establishing environmental regulations. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions To evaluate the effectiveness, tolerability, and safety of topical amitriptyline as a potential route of administration for the management of burning mouth syndrome.Burning mouth syndrome is a complex, idiopathic, and debilitating orofacial pain disorder that impairs quality of life, with a prevalence of up to 18% in menopausal women. Available drugs to alleviate its burning sensation have inconsistent and limited efficacy. Given its physicochemical properties, excellent tolerability, and ability to target peripheral pathways, topical amitriptyline seems a promising mechanistically specific analgesic drug for burning mouth syndrome.In this retrospective cross‐sectional real‐world evidence study, patients with burning mouth syndrome who were prescribed topical amitriptyline for 8 weeks were identified. Eligibility criteria stemmed from ICHD‐3, ICOP, and consensus definitions. The primary outcome measure was mean daily pain intensity (on a 0–10 scale); secondary outcomes included adverse events and patient global impression of improvement. Data are given as the mean ± SD.A total of 15 patients fulfilling the eligibility criteria were included and analyzed. Mean daily pain was 6.7 ± 2.1 at baseline and 3.7 ± 2.3 after treatment, with a mean reduction of 3.1 ± 2.8 (p = 0.002). Half of the patients experienced a decrease in pain by at least 50% (p = 0.008). Several mild adverse events were reported, such as somnolence or dry mouth.Topical amitriptyline may be a safe and potent route of administration in the treatment of burning mouth syndrome, a hypothesis to be tested in further controlled trials. [ABSTRACT FROM AUTHOR]

The open-channel block of N-methyl-D-aspartate receptors (NMDARs) and their calcium-dependent desensitization (CDD) represent conventional mechanisms of glutamatergic synapse regulation. In neurotrauma, neurodegeneration, and neuropathic pain the clinical benefits of cure with memantine, ketamine, Mg2+, and some tricyclic antidepressants are often attributed to NMDAR open-channel block, while possible involvement of NMDAR CDD in the therapy is not well established. Here the effects of selective high-affinity sodium-calcium exchanger (NCX) isoform 1 inhibitor, SEA0400, on NMDA-activated whole-cell currents and their block by amitriptyline, desipramine and clomipramine recorded by patchclamp technique in cortical neurons of primary culture were studied. We demonstrated that in the presence of extracellular Ca2+, 50 nM SEA0400 caused a reversible decrease of the steady-state amplitude of NMDAR currents, whereas loading neurons with BAPTA or the removal of extracellular Ca2+ abolished the effect. The decrease did not exceed 30% of the amplitude and did not depend on membrane voltage. The external Mg2+ block and 50 nM SEA0400 inhibition of currents were additive, suggesting their independent modes of action. In the presence of Ca2+ SEA0400 speeded up the decay of NMDAR currents to the steady state determined by CDD. The measured IC50 value of 27 nM for SEA0400-induced inhibition coincides with that for NCX1. Presumably, SEA0400 effects are induced by an enhancement of NMDAR CDD through the inhibition of Ca2+ extrusion by NCX1. SEA0400, in addition, at nanomolar concentrations could interfere with Ca2+-dependent effect of tricyclic antidepressants. In the presence of 50 nM SEA0400, the IC50s for NMDAR inhibition by amitriptyline and desipramine increased by about 20 folds, as the Ca2+-dependent NMDAR inhibition disappeared. This observation highlights NCX1 involvement in amitriptyline and desipramine effects on NMDARs and unmasks competitive relationships between SEA0400 and these antidepressants. Neither amitriptyline nor desipramine could affect NCX3. The open-channel block of NMDARs by these substances was not affected by SEA0400. In agreement, SEA0400 did not change the IC50 for clomipramine, which acts as a pure NMDAR open-channel blocker. Thus, NCX seems to represent a promising molecular target to treat neurological disorders, because of the ability to modulate NMDARs by decreasing the open probability through the enhancement of their CDD. [ABSTRACT FROM AUTHOR]

Afferent synapses between inner hair cells (IHCs) and the type I spiral ganglion neurons (SGNs) in the cochlea provide over 95% of sensory signals for auditory perception in the brain. However, these afferent synapses are particularly vulnerable to damage, for example from excitotoxicity, and exposure to noise in the environment which often leads to noise‐induced cochlear synaptopathy (NICS). In this study, we simulated excitotoxic trauma by incubating kainic acid, a non‐desensitizing agonist for AMPA type glutamate receptors on cultured cochleae. The possible protective effects of amitriptyline against NICS were examined. We found that, in IHCs, amitriptyline reversed the decrease of Ca2+ current and exocytosis caused by excitotoxic trauma. In SGNs, amitriptyline promoted the recovery of neurite loss caused by excitotoxic trauma. Furthermore, we found that the protective effects of amitriptyline are likely mediated by suppressing apoptosis factors that were upregulated during excitotoxic trauma. In conclusion, our results suggest that amitriptyline could protect afferent synapses in the cochlea from NICS, making it a potential drug candidate for hearing protection. [ABSTRACT FROM AUTHOR]

Background: The use of potentially inappropriate medications (PIMs) is associated with increased risk of hospitalizations and emergency room visits and varies by racial and ethnic subgroups. Medicare's nationwide medication therapy management (MTM) program requires that Part D plans offer an annual comprehensive medication review (CMR) to all beneficiaries who qualify, and provides a platform to reduce PIM use. The objective of this study was to assess the impact of CMR on PIM discontinuation in Medicare beneficiaries and whether this differed by race or ethnicity. Methods: Retrospective cohort study of community‐dwelling Medicare Part D beneficiaries ≥66 years of age who were eligible for MTM from 2013 to 2019 based on 5% Medicare fee‐for‐service claims data linked to the 100% MTM data file. Among those using a PIM, MTM‐eligible CMR recipients were matched to non‐recipients via sequential stratification. The probability of PIM discontinuation was estimated using regression models that pooled yearly subcohorts accounting for within‐beneficiary correlations. The most common PIMs that were discontinued after CMR were reported. Results: We matched 24,368 CMR recipients to 24,368 CMR non‐recipients during the observation period. Median age was 74–75, 35% were males, most were White beneficiaries (86%–87%), and the median number of PIMs was 1. In adjusted analyses, CMR receipt was positively associated with PIM discontinuation (adjusted relative risk [aRR]: 1.26, 95% CI: 1.20–1.32). There was no evidence of differential impact of CMR by race or ethnicity. The PIMs most commonly discontinued after CMR were glimepiride, zolpidem, digoxin, amitriptyline, and nitrofurantoin. Conclusions: Among Medicare beneficiaries who are using a PIM, CMR receipt was associated with PIM discontinuation, suggesting that greater CMR use could facilitate PIM reduction for all racial and ethnic groups. [ABSTRACT FROM AUTHOR]

Previous literature suggests that sphingolipids may impact systemic coagulation and platelet aggregation, thus modulating the risks of thrombotic events. The goal of this investigation was to evaluate the role of serum sphingolipids on intrinsic platelet function to assess whether pharmacologic manipulation of sphingolipid metabolites would impact platelet aggregability. C57BL/6J mice were injected with either normal saline, 1 mg/kg FTY720 (synthetic sphingosine-1-phosphate [S1P] receptor analog), or 5 mg/kg SLM6031434 (sphingosine kinase two inhibitor). Mice were sacrificed at 6 h and whole blood (WB) was collected for impedance aggregometry assessing platelet responsiveness to arachidonic acid or adenosine diphosphate. Ex vivo studies utilized WB or platelet-rich plasma that was pretreated with S1P, FTY720, amitriptyline, or d-sphingosine then analyzed by aggregability and flow cytometry for platelet and platelet-derived microvesicle characteristics. FTY720 and SLM6031434 pretreated induced similar arachidonic acid and adenosine diphosphate–mediated platelet aggregation as controls. Ex vivo WB and platelet-rich plasma treatment with S1P, FTY720, amitriptyline and d-sphingosine did not impact platelet aggregation. The percentages of CD41+, CD62P+ and CD41+/ceramide+, CD62P+/ceramide + platelets, and platelet-derived microvesicle were not significantly different between amitriptyline-treated and normal saline-treated cohorts. Sphingolipid modulating agents, such as FTY720, SLM6031434, S1P, amitriptyline, ceramide, and d-sphingosine do not appear to independently impact platelet aggregation in murine models. [ABSTRACT FROM AUTHOR]

Amitriptyline is a tricyclic antidepressant widely used in clinical practice for the treatment of an-xiety and depression and chronic pain. These drugs have a multifaceted effect on cellular processes. One of their targets is sigma-1 receptors. Sigma-1 receptors are molecular chaperones located in the membrane of the endoplasmic reticulum; they are characterized by a unique structure and pharmacological profile. Sigma-1 receptors regulate many cellular processes in health and disease, including processes of Ca2+ signaling. Using Fura-2AM fluorescent Ca2+ probe, we showed for the first time that sigma-1 receptor agonist, the antidepressant amitriptyline, significantly suppresses Ca2+ mobilization from the intracellular Ca2+ stores and subsequent store-dependent Ca2+ entry into cells caused by inhibitors of endoplasmic Ca2+ ATPases thapsigargin and cyclopiazonic acid, as well as the disulfide-containing immunomodulators glutoxim and molixan, in rat peritoneal macrophages. The results indicate the participation of sigma-1 receptors in the complex signaling cascade caused by glutoxim or molixan, leading to an increase in intracellular Ca2+ concentration in macrophages. Data also indicate that sigma-1 receptors participate in the regulation of store-dependent Ca2+ entry in macrophages. [ABSTRACT FROM AUTHOR]

To describe the need and effectiveness of acute and preventive medications in a series of 100 consecutive patients referred due to COVID-19-related headaches. Patients were aged 48.0 (standard deviation (SD): 12.4), 84% were female, and 56% had a prior history of headache. The most common headache phenotype was holocranial (63%), frontal (48%), pressing (75%), of moderate intensity (7 out of 10), and accompanied by photophobia (58%). Acute medication was required by 93%, with paracetamol (46%) being the most frequently used drug, followed by ibuprofen (44%). The drugs with the highest proportion of a 2 h pain-freedom response were dexketoprofen (58.8%), triptans (57.7%), and ibuprofen (54.3%). Preventive treatment was required by 75% of patients. The most frequently used drugs were amitriptyline (66%), anesthetic blockades (18%), and onabotulinumtoxinA (11%). The drugs with the highest 50% responder rate were amitriptyline (45.5%), mirtazapine (50%), and anesthetic blockades (38.9%). The highest 75% responder rate was experienced following onabotulinumtoxinA (18.2%). In conclusion, most patients required acute medication, with triptans and non-steroidal anti-inflammatory drugs achieving the best responses. Three-quarters of patients required preventive medication. The most frequently used drug was amitriptyline, which obtained the best results. In some treatment-resistant patients, anesthetic blockades and onabotulinumtoxinA were also beneficial. [ABSTRACT FROM AUTHOR]

Abstract Burning mouth syndrome (BMS) is characterized by burning sensations in the oral region without corresponding abnormalities and is often accompanied by uncomfortable sensations. Herein, we present cases of BMS in which the remaining uncomfortable sensations improved with perospirone augmentation with clonazepam. Case 1: A 61‐year‐old man complained of a burning pain in his tongue, a sensation of dryness and discomfort as if his tongue was sticking to a palatal plate. With the diagnosis of BMS, psychopharmacotherapy was initiated with amitriptyline. At the dose of amitriptyline 50 mg, the pain lessened but uncomfortable sensations persisted. Further attempts to alleviate symptoms by combining aripiprazole with amitriptyline, aripiprazole with mirtazapine, or aripiprazole with clonazepam were limited; however, nearly all symptoms were relieved by a combination of perospirone 8.0 mg with clonazepam 1.5 mg. Case 2: A 51‐year‐old woman complained of a burning sensation along with oral dryness and crumb‐like feeling on her tongue. She was diagnosed with BMS and began treatment with amitriptyline. Her burning sensation improved at the dose of 25 mg, but uncomfortable sensations persisted. Augmentation of amitriptyline with aripiprazole, aripiprazole either with valproate, mirtazapine, or clonazepam failed to produce a significant improvement. However, a regimen of perospirone 6.0 mg and clonazepam 1.5 mg relieved the crumb‐like sensation and pain and culminated in a stabilized condition. The reported cases suggested that multiple approaches targeting the dopaminergic circuit in basal ganglia involving the serotoninergic and GABA systems, through the administration of perospirone with clonazepam is an effective adjunctive treatment for the remaining uncomfortable sensations in patients with BMS.

Abstract Background Chronic post-penile prosthesis pain is de novo pain persisting > 2 months post-operatively. This pain is inadequately reported, poorly understood and undermanaged. The purpose of this current pilot study was to improvise a medical approach to alleviate the condition and assess the combination of Pregabalin and Amitriptyline in its management. Results The study enrolled 9 patients complaining of idiopathic penile, pelvic, or scrotal pain persisting > 2 months after penile prosthesis implantation. Patients were prescribed pregabalin 75mg/12h (escalated after 1 week to 150mg/12h upon demand) and Amitriptyline 25mg once daily for 3 months. The pain was reassessed after 10, 30 and 100 days. The dose of pregabalin required and the side effects of the medication were noted. Findings revealed a significant decrease in pain duration (p = 0.007), frequency (p

Patients with mutations that alter the function of the sodium channel SCN8A present with a range of clinical features, including mild to severe seizures, developmental delay, intellectual disability, autism, feeding dysfunction, motor impairment, and hypotonia. In an effort to identify compounds that could be potentially beneficial in SCN8A-associated epilepsy, Atkin et al. conducted an in vitro screen which resulted in the identification of 90 compounds that effectively reduced sodium influx into the cells expressing the human SCN8A R1872Q mutation. The top compounds that emerged from this screen included amitriptyline, carvedilol, and nilvadipine. In the current study, we evaluated the ability of these three compounds to increase resistance to 6 Hz or pentylenetetrazole (PTZ)-induced seizures in wild-type CF1 mice and in a mouse line expressing the human SCN8A R1620L mutation. We also evaluated the effects of fenfluramine administration, which was recently associated with a 60%–90% decrease in seizure frequency in three patients with SCN8Aassociated epilepsy. While amitriptyline, carvedilol, and fenfluramine provided robust protection against induced seizures in CF1 mice, only carvedilol was able to significantly increase resistance to 6 Hz- and PTZ-induced seizures in RL/+ mutants. These results provide support for further evaluation of carvedilol as a potential treatment for patients with SCN8A mutations. [ABSTRACT FROM AUTHOR]

A method for the determination of amitriptyline, a tricyclic antidepressant, in human urine by immunosensors has been developed using supramolecular systems based on hexamolybdenum cluster complexes. These complexes have electrochemical activity and give a stable analytical signal, which was used in the development of amperometric immunosensors. Luminescence and dynamic light scattering methods were used to demonstrate the formation of a supramolecular system of self-organized hexamolybdenum nanoparticles and chitosan molecules. A composite material based on hexamolybdenum cluster complexes in combination with reduced graphene oxide has been developed. The working range of amitriptyline concentrations to be determined by an amperometric immunosensor was 1 × 10–9–1 × 10–4 M, the limit of determination was at a level of 5 × 10–10 M, and the amitriptyline content of urine samples was at a level of (n – 7) × 10–8 M. A comparison of the results of analysis performed using an amperometric immunosensor and a fluorescence polarization immunoassay showed the absence of significant systematic errors. The ability to determine amitriptyline in biological fluids makes it possible to select an optimal therapeutic dose of the drug, that is, to develop approaches to creating personalized medicine. [ABSTRACT FROM AUTHOR]

Burning mouth syndrome (BMS) is characterized by burning sensations in the oral region without corresponding abnormalities and is often accompanied by uncomfortable sensations. Herein, we present cases of BMS in which the remaining uncomfortable sensations improved with perospirone augmentation with clonazepam. Case 1: A 61‐year‐old man complained of a burning pain in his tongue, a sensation of dryness and discomfort as if his tongue was sticking to a palatal plate. With the diagnosis of BMS, psychopharmacotherapy was initiated with amitriptyline. At the dose of amitriptyline 50 mg, the pain lessened but uncomfortable sensations persisted. Further attempts to alleviate symptoms by combining aripiprazole with amitriptyline, aripiprazole with mirtazapine, or aripiprazole with clonazepam were limited; however, nearly all symptoms were relieved by a combination of perospirone 8.0 mg with clonazepam 1.5 mg. Case 2: A 51‐year‐old woman complained of a burning sensation along with oral dryness and crumb‐like feeling on her tongue. She was diagnosed with BMS and began treatment with amitriptyline. Her burning sensation improved at the dose of 25 mg, but uncomfortable sensations persisted. Augmentation of amitriptyline with aripiprazole, aripiprazole either with valproate, mirtazapine, or clonazepam failed to produce a significant improvement. However, a regimen of perospirone 6.0 mg and clonazepam 1.5 mg relieved the crumb‐like sensation and pain and culminated in a stabilized condition. The reported cases suggested that multiple approaches targeting the dopaminergic circuit in basal ganglia involving the serotoninergic and GABA systems, through the administration of perospirone with clonazepam is an effective adjunctive treatment for the remaining uncomfortable sensations in patients with BMS. This is the first report introduced cases of BMS where patients' remained discomfort was ameliorated by perospirone augmentation with clonazepam, which approaches multiply to dopaminergic circuit in basal ganglia involving serotoninergic and GABA system. It may be as effective adjunctive treatment for the remaining uncomfortable sensations in the patients with BMS. [ABSTRACT FROM AUTHOR]

BACKGROUND: Functional dyspepsia is a disorder of gut-brain interaction that has the potential to impact aviation performance. Proton pump inhibitors are well-tolerated but are only effective in one half of cases. Second-line treatments, including tricyclic antidepressants, are associated with drowsiness and are not routinely approved for use in aviators. We present a case of a Naval Flight Officer with functional dyspepsia who was successfully treated with amitriptyline and returned to flying status. CASE REPORT: A 23-yr-old male Naval Flight Officer presented with postprandial fullness and epigastric pain. His symptoms were refractory to trials of acid suppression and lifestyle modification. An extensive evaluation by Gastroenterology, including upper endoscopy, did not reveal an organic cause of his symptoms and he was diagnosed with functional dyspepsia. The patient's symptoms resolved with a trial of amitriptyline. Neuropsychological testing demonstrated no medication effect on cognitive performance. A waiver to resume flying duties on amitriptyline was submitted to the Naval Aerospace Medical Institute and was approved. DISCUSSION: We present the second known waiver issued in U.S. Naval aviation history for the use of amitriptyline to treat a gastrointestinal disorder. Amitriptyline is not commonly waived due to the potential for unacceptable cognitive side-effects in the flight environment. However, neuropsychological testing to assess for a possible medication effect on performance can be used to inform an aeromedical disposition and, in this case, allowed for a return to flight status. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Painful peripheral diabetic neuropathy (PRDN) is a common disabling condition. Pregabalin and amitriptyline are commonly prescribed as the first-line for PPDN despite the contradicting recommendations. There is a need to inform the scientific community regarding first-line pain control among patients with PPDN. This meta-analysis assessed pregabalin and amitriptyline effects on PPDN. PATIENTS AND METHODS: We searched PubMed, MEDLINE, Cochrane Library, EBSCO, and Google Scholar; the terms used were amitriptyline, pregabalin, painful diabetic neuropathy, antidepressant, gabapentinoids, quality of life, and adverse events. Boolean operators like AND, and OR were used. Six hundred and thirty-one studies were retrieved, and 37 full texts were screened. However, only six randomized controlled trials fulfilled the inclusion and exclusion criteria. RESULTS: No significant statistical differences between amitriptyline and pregabalin regarding pain score and significant pain reduction (odd ratio, -0.82, 95% CI, -2.21-0.58, and odd ratio, 1.16, 95% CI, 0.76-1.76 respectively). Quality of life, total adverse events, and drug discontinuation were not different between the two drugs (odd ratio, 0.89, 95% CI, -2.11-3.89, odd ratio, 0.98, 95% CI, 0.52-1.85, and odd ratio, 0.51, 95% CI, 0.08-3.15, respectively). CONCLUSIONS: No significant statistical differences between amitriptyline and pregabalin regarding their effects on pain and quality of life. The drugs showed similar total adverse events and drug withdrawal. Further larger real-world studies are needed. [ABSTRACT FROM AUTHOR]

Psychiatric drugs do not vanish after being carried to wastewater treatment plants by the urine or feces of patients and, a variable portion of their dose and also unused or expired drugs are lost to the environment. This is because the technology of plants is not intended to eradicate pharmaceuticals and their metabolites. Above all, psychotropics can change population dynamics and behavior at lower doses. We believe that antipsychotics have not gotten enough attention when it comes to drug pollution and that their importance as environmental pollutants has been underestimated. An innovative approach to eliminating pharmaceutical pollutants from water is the application of advanced oxidation methods. Among these oxidation methods are photocatalysis, ozonation, UV/hydrogen peroxide oxidation, and photo-Fenton oxidation. Photocatalytic degradation of pharmaceuticals is now the most widely used method since it is affordable and ecologically beneficial due to the reusable nature of the photocatalyst. When light is absorbed during photocatalytic degradation, electrons in the valence band (VB) get excited and migrate into the conduction band (CB). Consequently, hydroxyl radicals (•OH) are produced by VB's holes carrying out oxidation processes on photocatalyst surfaces. The charge difference between the two bands encourages reduction reactions by CB electrons at the surface. To perform successfully, a photocatalyst has to have enough surface-active sites, a favorable band edge location, modest bandgap energy, increased charge separation, and charge transfer. Due to the above-mentioned concerns, the investigation and analysis of the photocatalytic degradation of six psychiatric drugs—carbamazepine, sertraline, amisulpride, amitriptyline, diazepam, and alprazolam—are the main objectives of this review. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a global health concern with the acid sphingomyelinase (ASM)/ceramide (CE) pathway and the NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome identified as pivotal players in lipid disorders and inflammation. This study explores the interaction mechanism between the ASM/CE pathway and NLRP3 in NAFLD cell models, aiming to understand the impact of amitriptyline (Ami), an ASM inhibitor, on lipid deposition and hepatocyte injury by regulating the ASM/CE-NLRP3 pathway. Methods: HepG2 and HL-7702 cells were exposed to free fatty acids (FFAs) to establish the NAFLD model. The cells were divided into 5 groups: control group, model group, Ami group, tumor necrosis factoralpha (TNF-α) group, and Ami + TNF-α group. Intracellular lipid droplets were visualized using Oil Red O staining, and Western blot analysis quantified ASM, NLRP3, and caspase 1 protein expression. Enzyme linked immunosorbent assay (ELISA) was measured CE and ASM levels, while qRT-PCR assessed mRNA expression. The apoptotic rate was evaluated by flow cytometry (FCM). Results: Following FFAs incubation, significant increases in ASM and CE levels were observed in HepG2 and HL-7702 cells, accompanied by elevated expression of NLRP3, and caspase 1, and IL-1ß. TNF-α treatment further amplified these indicators. Ami demonstrated a reduction in lipid deposition, suppressed ASM/CE pathway activation, downregulated NLRP3 and caspase 1 expression, and improved apoptosis. Additionally, MCC950, a selective inhibitor of the NLRP3, mitigated NLRP3, caspase 1, and IL-1β expression, alleviating lipid deposition and apoptosis in the NAFLD cell model. Conclusion: The ASM/CE-NLRP3 pathway in NAFLD cells promotes hepatocyte steatosis, inflammation, and cell damage. Ami emerges as a promising therapeutic agent by inhibiting the ASM/CE-NLRP3 pathway, underscoring its potential as a key target for NAFLD treatment. [ABSTRACT FROM AUTHOR]

Objective: In this retrospective cross‐sectional real‐world evidence study from the Danish Headache Center (DHC), a national tertiary headache center in Denmark, we sought to identify potential pharmacological agents for the treatment of new daily persistent headache (NDPH). Background: NDPH is an enigmatic headache disorder with abrupt onset and chronic duration for which evidence‐based treatments are lacking. NDPH is a diagnosis of exclusion, for which secondary headaches must be ruled out and the etiology remains idiopathic. The sparse investigations of this disorder have not yielded a pathophysiological basis and no effective treatment for NDPH has been found. Methods: All patients with an NDPH diagnosis at the DHC were enrolled (n = 64). First, we reviewed the records of all patients with an NDPH diagnosis to evaluate whether they fulfilled the diagnostic criteria. Next, we extracted all the trialled acute and prophylactic pharmacological interventions for the included patients. Then, pharmacological interventions that had been tried in ≥ 20 patients were analyzed post hoc with efficacy as the outcome, which was stratified in five effect categories ("no effect," "partial effect," "full effect," "partial effect and cessation due to adverse events," and "full effect and cessation due to adverse events"). Descriptive statistical analysis was performed, and the results were schematically presented (see Table 2). Results: Fifty‐one patients out of 64 were found to fulfill NDPH criteria and were included in the study. The drugs tried by ≥ 20 patients were amitriptyline (n = 34), candesartan (n = 27), and mirtazapine (n = 20). No patients experienced a complete effect with these drugs while 9% (3/34), 26% (7/27), and 15% (3/20) experienced a partial effect with no adverse events that led to treatment discontinuation, respectively. The remaining patients experienced either no effect or a partial effect with adverse events leading to treatment discontinuation. Conclusion: In this study we add real‐world evidence to suggest that prophylactic drugs conventionally used for treating chronic migraine and chronic tension‐type headache have limited utility for treating NDPH; however, a partial response in 26% of patients using candesartan and 15% of patients using mirtazapine warrants further investigation in randomized double‐blinded placebo‐controlled trials. Plain Language Summary: New daily persistent headache (NDPH) is a chronic headache for which the cause remains unknown and with no established evidence‐based treatments. In our retrospective study from the Danish Headache Center, we explored potential medication solutions for NDPH in 51 patients. Candesartan and mirtazapine showed some benefit for patients with NDPH in 26% and 15% of our patients, respectively, highlighting a need for further investigations into the potential benefits of these drugs. [ABSTRACT FROM AUTHOR]

Hydrophilic interaction liquid chromatography (HILIC) has been widely applied to challenging analysis in biomedical and pharmaceutical fields, bridging the gap between normal‐phase high‐performance liquid chromatography and reversed‐phase high‐performance liquid chromatography (RP‐HPLC). This paper comprehensively explores the retention mechanisms of amitriptyline and its impurities A, B, C, D, F, and G on amide, amino, diol, and silica columns. Dual HILIC/RP‐HPLC retention mechanisms were developed, and transitional points between HILIC and RP‐HPLC mechanisms were calculated on amide, diol, and silica columns. Adsorption and partition contributions to overall retention mechanisms were evaluated using Python software in HILIC and RP‐HPLC regions. The cation exchange mechanism dominates overall retention for ionized analytes in the silica column (R2 > 0.995), whereas the retention of ionized analytes increases with pH. Impacts of acetonitrile content, buffer ionic strength, and pH, along with their interactions on the retention of ionized analytes in the silica column, were determined using the chemometric approach. Acetonitrile content showed the most significant impact on the retention mechanisms. These findings highlight that a detailed investigation into retention mechanisms provides notable insights into factors influencing analyte retention and separation, promising valuable guidance for future analysis. [ABSTRACT FROM AUTHOR]

Practical relevance: Chronic pain is a significant welfare concern in cats, and neuropathic pain, which arises from aberrant processing of sensory signals within the nervous system, is a subcategory of this type of pain. To comprehend this condition and how multimodal pharmacotherapy plays a central role in alleviating discomfort, it is crucial to delve into the anatomy of nociception and pain perception. In addition, there is an intricate interplay between emotional health and chronic pain in cats, and understanding and addressing the emotional factors that contribute to pain perception, and vice versa, is essential for comprehensive care. Clinical approach: Neuropathic pain is suspected if there is abnormal sensation in the area of the distribution of pain, together with a positive response to trial treatment with drugs effective for neuropathic pain. Ideally, this clinical suspicion would be supported by confirmation of a lesion at this neurolocalisation using diagnostic modalities such as MRI and neuroelectrophysiology. Alternatively, there may be a history of known trauma at that site. A variety of therapies, including analgesic, anti-inflammatory and adjuvant drugs, and neuromodulation (eg, TENS or acupuncture), can be employed to address different facets of pain pathways. Aim: This review article, aimed at primary care/ general practitioners, focuses on the identification and management of neuropathic pain in cats. Three case vignettes are included and a structured treatment algorithm is presented to guide veterinarians in tailoring interventions. Evidence base: The review draws on current literature, where available, along with the author's extensive experience and research. [ABSTRACT FROM AUTHOR]

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. Highlights: Acupuncture showed better improvement than sham acupuncture in reducing headache frequency of tension-type headache (TTH), but the lack of comparisons between acupuncture and first-line drugs impedes recommendation of acupuncture for TTH. Our indirect treatment comparison meta-analysis found similar effect between acupuncture and tricyclic antidepressants (TCAs) in reducing TTH frequency with very low certainty of evidence. Similar effect between acupuncture and TCAs were also observed in reducing headache intensity with very low certainty of evidence. Acupuncture had a lower rate of adverse events than amitriptyline with very low certainty of evidence. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionThis study aims to analyze the clinical effects of combining carbamazepine and amitriptyline in the treatment of diabetic neuropathy with concurrent diabetic foot.A total of 120 diabetic neuropathy patients treated at our hospital from June 2022 to November 2023 were included in the study. Patients meeting the inclusion criteria were registered, and their basic data were collected. The patients were randomly divided into two groups: the control group treated with amitriptyline and the study group treated with a combination of carbamazepine and amitriptyline.The study group demonstrated significantly better clinical efficacy compared to the control group (p < 0.05). There were no significant differences in psychological status and pain perception before treatment between the two groups (p > 0.05). However, post-treatment, the study group showed improved psychological status, reduced pain perception, and overall better quality of life in both physiological and psychological dimensions compared to the control group (p < 0.05).The combined use of carbamazepine and amitriptyline in the treatment of diabetic neuropathy with concurrent diabetic foot yields positive clinical outcomes. It effectively alleviates symptoms, improves psychological well-being, reduces pain sensation, and enhances overall quality of life. These findings can guide physicians in adopting a more evidence-based treatment approach and provide patients with more effective individualized treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Pediatric migraine prophylaxis is indicated when headaches are frequent and/or disabling. We aimed to conduct a study to compare the efficacy of cinnarizine and amitriptyline in pediatric migraine prophylaxis. Methods: In a randomized, double-blind trial, patients aged 4–17 years with migraine who were eligible for prophylaxis enrolled. The primary outcome was a reduction response rate of ≥50% with p < 0.005 with respect to headache characteristics. The secondary outcome was migraine disability assessment. We evaluated patients every four weeks for three months: T1: week 4, T2: week 8 and T3: week 12. The safety profile was also assessed. Results: Thirty patients were randomly assigned to each group. However, 43 patients completed the trial. Headache frequency decreased in amitriptyline group more effectively in T1 (p = 0.004). Amitriptyline was more successful in reducing the headache duration in all three periods (p < 0.005). There was no significant difference in severity improvement and reducing disability score between the two groups (p > 0.005). No serious adverse events were observed. Conclusions: Both medications are effective in ameliorating migraine headaches and related disabilities. However, amitriptyline appears be a preferable option over cinnarizine, given its faster onset of action, efficacy in reducing headache duration and longer-lasting effects. Trial Registration: The study was registered with the Iranian Registry of Clinical Trials (IRCT) under the code IRCT-20191112045413N1. [ABSTRACT FROM AUTHOR]

Antidepressant drugs play a crucial role in the treatment of mental health disorders, but their efficacy and safety can be compromised by drug degradation. Recent reports point to several drugs found in concentrations ranging from the limit of detection (LOD) to hundreds of ng/L in wastewater plants around the globe; hence, antidepressants can be considered emerging pollutants with potential consequences for human health and wellbeing. Understanding and implementing effective degradation strategies are essential not only to ensure the stability and potency of these medications but also for their safe disposal in line with current environment remediation goals. This review provides an overview of degradation pathways for amitriptyline, a typical tricyclic antidepressant drug, by exploring chemical routes such as oxidation, hydrolysis, and photodegradation. Connex issues such as stability-enhancing approaches through formulation and packaging considerations, regulatory guidelines, and quality control measures are also briefly noted. Specific case studies of amitriptyline degradation pathways forecast the future perspectives and challenges in this field, helping researchers and pharmaceutical manufacturers to provide guidelines for the most effective degradation pathways employed for minimal environmental impact. [ABSTRACT FROM AUTHOR]

Background: Fibromyalgia is a common condition characterised by chronic widespread musculoskeletal pain and central sensitivity features. Appropriate management requires a multidisciplinary approach prioritising non‐pharmacological strategies. Evidence‐based fibromyalgia medications are not always easily available, effective or tolerated. Aim: To characterise actual medication usage in Australian fibromyalgia patients. Methods: Demographic and clinical data, including medication use information, were gathered by chart review from patients attending the Monash Fibromyalgia Clinic between January 2019 and June 2022. Eligible patients were invited to complete an anonymous questionnaire between June and August 2022 to assess current therapeutic use. The questionnaire assessed fibromyalgia clinical features by using the Revised Fibromyalgia Impact Questionnaire and the 2016 modified American College of Rheumatology Fibromyalgia criteria. Results: The chart review included 474 patients, and 108 participants completed the questionnaire. Most chart review (78.7%) and questionnaire participants (85.2%) reported using at least one medication for their fibromyalgia. 48.5% of chart review patients and 58.3% of questionnaire participants reported using at least one evidence‐based medication, usually amitriptyline, duloxetine or pregabalin. However, the most common individual medications for questionnaire participants were non‐steroidal anti‐inflammatory drugs (48.2%), paracetamol (59.3%) and opioids (34.3%), with most opioids being typical opioids. Among questionnaire participants, 14.8% reported using cannabinoids, and 70.4% reported using at least one supplement, vitamin or herbal/naturopathic preparation. Not all medication or substance use was recorded during clinic appointments. Conclusion: Fibromyalgia patients engage in various pharmacotherapeutic strategies that are not always evidence‐based or disclosed to their treating clinicians. [ABSTRACT FROM AUTHOR]

Introduction: In the DELIVER study, eptinezumab reduced monthly migraine days (MMDs) more than placebo in patients with 2–4 prior preventive migraine treatment failures. This post hoc analysis evaluated the efficacy of eptinezumab across the 24-week placebo-controlled period of the DELIVER study in subgroups defined by prior treatment failure type. Methods: DELIVER (NCT04418765) randomized adults with migraine to eptinezumab 100 mg, 300 mg, or placebo, administered intravenously every 12 weeks. Changes from baseline in MMDs and percentages of patients with ≥ 50% reduction from baseline in MMDs (≥ 50% migraine responder rates [MRRs]) were summarized in subgroups of patients defined by prior treatment failure type. Subgroups were not mutually exclusive and included patients for whom topiramate, beta blockers (metoprolol, propranolol), amitriptyline, and/or flunarizine had failed. Results: Across Weeks 1–12 in all subgroups, patients treated with eptinezumab experienced greater reductions from baseline in MMDs than those receiving placebo (reductions ranged from 4.5–5.5 vs 1.6–2.4, respectively), with larger reductions over Weeks 13–24. Similarly, ≥ 50% MRRs were consistently higher with eptinezumab than placebo and increased following a second infusion. Conclusion: In all subgroups, regardless of prior preventive treatment failure type, eptinezumab demonstrated greater reductions in MMDs and higher MRRs compared with placebo. Trial Registration: ClinicalTrials.gov (Identifier: NCT04418765). [ABSTRACT FROM AUTHOR]

Aim: In the current study, a multivariate FTIR method and two different UV spectrophotometric methods were employed for the simultaneous determination of Amitriptyline Hydrochloride (ATH) and Propranolol Hydrochloride (PPH) in their combined formulation. Materials and Methods: The multivariate FTIR method based on the use of Classical Least Squares (CLS) was developed and executed in the lab solutions software for the simultaneous determination of ATH and PPH. CLS model was performed in the wavenumber range of 2550.04-3600.12 cm-1 and 969.64-1757 cm-1. In addition, two UV spectroscopic methods, namely absorbance correction method and crammer's matrix method were developed and validated in the concentration ranges of 2-10µg/mL and 5-55µg/mL for ATH and PPH respectively. Results: The statistical parameters obtained from the applied multivariate FTIR-CLS model revealed the model accuracy and the assay results of ATH and PPH were found to be 92.32 (%w/w) and 97.35 (%w/w) respectively. The developed UV spectroscopic methods were validated as per ICH guidelines and all the validation parameters were found to be within the acceptance criteria. Conclusion: The methods employed in the current study were found to simple, economical, accurate and do not require any prior separation. [ABSTRACT FROM AUTHOR]