A comparative study on prophylactic efficacy of cinnarizine and amitriptyline in childhood migraine: a randomized double-blind clinical trial.

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.

Platelet Function is Independent of Sphingolipid Manipulation.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Sphingolipid modulating agents, such as FTY720, SLM6031434, S1P, amitriptyline, ceramide, and d-sphingosine do not appear to independently impact platelet aggregation in murine models.

Amitriptyline and cholecalciferol amend hippocampal histological structure and myelination during stress in Wistar rats via regulating miR200/BMP4/Olig-2 signaling.

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.

Clinical effects of combined use of carbamazepine and amitriptyline in the treatment of diabetic neuropathy with concurrent diabetic foot.

OBJECTIVE: This study aims to analyze the clinical effects of combining carbamazepine and amitriptyline in the treatment of diabetic neuropathy with concurrent diabetic foot. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

An Overview of Degradation Strategies for Amitriptyline.

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.

Amitriptyline effectiveness in burning mouth syndrome: An in-depth case series analysis.

OBJECTIVES: To assess the effectiveness of amitriptyline (AMT), and to identify the determinants of the treatment's effectiveness in patients diagnosed with burning mouth syndrome (BMS). BACKGROUND: Treatment of BMS is challenging and no established treatment protocol is available. AMT may be an important treatment option, cout not all patients benefit from this drug. Studies assessing factors related to treatment response are valuable in improving decision-making. MATERIALS AND METHODS: This case series study examined the medical records of all patients diagnosed with BMS at an oral medicine unit in a university hospital from 2008 to 2022. The patients were divided into responders to AMT and non-responders to AMT. Data on demographic information, comorbidities, medications, types of symptoms and oral subsites affected were collected. Descriptive and bivariate analyses were conducted to assess the association between the independent variables and the outcome, using the Chi-squared test (P < .05). RESULTS: Three hundred and fourty-nine patients reported a burning mouth sensation, 50 of them (14.3%) being diagnosed with primary BMS. Of these, 35 were treated with AMT, and 26 (74.2%) responded significantly to AMT. All males responded to AMT, whereas only 67.9% of females responded. The mean dose of AMT among responders was 29.8 ± 12.3 mg, with most patients achieving a response with 25 mg (61.5% of patients), followed by 50 mg (23%). The concomitant use of an anticonvulsant resulted in non-response. CONCLUSIONS: AMT may be effective in BMS management for most patients.

An investigation of the potential effects of amitriptyline on polycystic ovary syndrome induced by estradiol valerate.

Polycystic ovarian syndrome (PCOS) is frequently observed in adolescent women and usually progresses with depression. The aim of this study was to examine the effects of amitriptyline (Ami), a drug used in the treatment of depression, in individuals with PCOS. Forty 12-week-old female Wistar albino rats were randomly divided into five groups: control, sham, PCOS, Ami, and PCOS + Ami. To induce the syndrome in the PCOS groups, a single dose of 4 mg/kg estradiol valerate was administered by intraperitoneal injection; 10 mg/kg Ami was administered by intraperitoneal injection for 30 days in the Ami groups. After 30 days, all the animals were sacrificed and blood, ovary, and brain tissues were collected and subjected to routine tissue processing. Stereological, histopathological analyses were performed on the ovarian sections, while luteinizing hormone (LH), follicle-stimulating hormone (FSH), catalase (CAT), and superoxide dismutase (SOD) levels were investigated in blood samples. The volume of the corpus luteum and preantral follicles increased in the PCOS group, while a decrease was determined in the number of antral follicles using stereological methods. Biochemical analysis revealed that FSH levels increased and CAT enzyme levels decreased in the PCOS group. Significant morphological changes were observed in ovaries from the PCOS group. The volume of the corpus luteum in the PCOS + Ami group decreased compared to the PCOS group. Serum FSH levels decreased in the PCOS + Ami group, while CAT enzyme levels increased compared to the PCOS group. Degenerative areas were also seen in the PCOS + Ami group ovaries. Ami administration was unable to sufficiently ameliorate the morphological and biochemical changes caused in the ovarian tissues by PCOS. In addition, this study is one of the few studies examining the effects of amitriptyline, an antidepressant frequently used in depression treatment of individuals with PCOS. We also observed firstly that use of amitriptyline caused PCOS-like ovarian morphology in healthy rat ovaries, while it had a healing effect by volume decreasing of cystic structures in the ovary with PCOS.

Amitriptyline efficacy in decreasing implant-induced foreign body reaction.

Beyond its actions on the nervous system, amitriptyline (AM) has been shown to lower inflammatory, angiogenic, and fibrogenic markers in a few pathological conditions in human and in experimental animal models. However, its effects on foreign body reaction (FBR), a complex adverse healing process, after biomedical material implantation are not known. We have evaluated the effects of AM on the angiogenic and fibrogenic components on a model of implant-induced FBR. Sponge disks were implanted subcutaneously in C57BL/6 mice, that were treated daily with oral administration of AM (5 mg/kg) for seven consecutive days in two protocols: treatment was started on the day of surgery and the implants were removed on the seventh day after implantation and treatment started 7 days after implantation and the implants removed 14 after implantation. None of the angiogenic (vessels, Vascular endothelial growth factor (VEGF), and interleukin-1ß (IL-1ß) or fibrogenic parameters (collagen, TGF-ß, and fibrous capsule) and giant cell numbers analyzed were attenuated by AM in 7-day-old implants. However, AM was able to downregulate angiogenesis and FBR in 14-day-old implants. The effects of AM described here expands its range of actions as a potential agent capable of attenuating fibroproliferative processes that may impair functionality of implantable devices.

Irradiation accelerates SARS-CoV-2 infection by enhancing sphingolipid metabolism.

Cancer patients who receive radiotherapy have a high risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, but the concrete reason remains unclear. Herein, we investigated the influence of irradiation on the vulnerability of cancer cells to SARS-CoV-2 using S pseudovirions and probed the underlying mechanism via RNA-seq and other molecular biology techniques. Owing to the enhancement of sphingolipid metabolism, irradiation accelerated pseudovirion infection. Mechanistically, irradiation induced the expression of acid sphingomyelinase (ASM), which catalyses the hydrolysis of sphingomyelin to ceramide, contributing to lipid raft formation and promoting SARS-CoV-2 invasion. Inhibition of lipid raft formation with methyl-ß-cyclodextrin (MßCD) or the tyrosine kinase inhibitor genistein and ASM suppression through small interfering RNA or amitriptyline (AMT) treatment abolished the enhancing effect of irradiation on viral infection. Animal experiments supported the finding that irradiation promoted SARS-CoV-2 S pseudovirion infection in A549 cell tumour-bearing BALB/c nude mice, whereas AMT treatment dramatically decreased viral infection. This study discloses the role of sphingolipid metabolism in irradiation-induced SARS-CoV-2 infection, thus providing a potential target for clinical intervention to protect patients receiving radiotherapy from COVID-19.

Amitriptyline inhibits bronchoconstriction and directly promotes dilatation of the airways.

INTRODUCTION: The standard therapy for bronchial asthma consists of combinations of acute (short-acting ß2-sympathomimetics) and, depending on the severity of disease, additional long-term treatment (including inhaled glucocorticoids, long-acting ß2-sympathomimetics, anticholinergics, anti-IL-4R antibodies). The antidepressant amitriptyline has been identified as a relevant down-regulator of immunological TH2-phenotype in asthma, acting-at least partially-through inhibition of acid sphingomyelinase (ASM), an enzyme involved in sphingolipid metabolism. Here, we investigated the non-immunological role of amitriptyline on acute bronchoconstriction, a main feature of airway hyperresponsiveness in asthmatic disease. METHODS: After stimulation of precision cut lung slices (PCLS) from mice (wildtype and ASM-knockout), rats, guinea pigs and human lungs with mediators of bronchoconstriction (endogenous and exogenous acetylcholine, methacholine, serotonin, endothelin, histamine, thromboxane-receptor agonist U46619 and leukotriene LTD4, airway area was monitored in the absence of or with rising concentrations of amitriptyline. Airway dilatation was also investigated in rat PCLS by prior contraction induced by methacholine. As bronchodilators for maximal relaxation, we used IBMX (PDE inhibitor) and salbutamol (ß2-adrenergic agonist) and compared these effects with the impact of amitriptyline treatment. Isolated perfused lungs (IPL) of wildtype mice were treated with amitriptyline, administered via the vascular system (perfusate) or intratracheally as an inhalation. To this end, amitriptyline was nebulized via pariboy in-vivo and mice were ventilated with the flexiVent setup immediately after inhalation of amitriptyline with monitoring of lung function. RESULTS: Our results show amitriptyline to be a potential inhibitor of bronchoconstriction, induced by exogenous or endogenous (EFS) acetylcholine, serotonin and histamine, in PCLS from various species. The effects of endothelin, thromboxane and leukotrienes could not be blocked. In acute bronchoconstriction, amitriptyline seems to act ASM-independent, because ASM-deficiency (Smdp1-/-) did not change the effect of acetylcholine on airway contraction. Systemic as well as inhaled amitriptyline ameliorated the resistance of IPL after acetylcholine provocation. With the flexiVent setup, we demonstrated that the acetylcholine-induced rise in central and tissue resistance was much more marked in untreated animals than in amitriptyline-treated ones. Additionally, we provide clear evidence that amitriptyline dilatates pre-contracted airways as effectively as a combination of typical bronchodilators such as IBMX and salbutamol. CONCLUSION: Amitriptyline is a drug of high potential, which inhibits acute bronchoconstriction and induces bronchodilatation in pre-contracted airways. It could be one of the first therapeutic agents in asthmatic disease to have powerful effects on the TH2-allergic phenotype and on acute airway hyperresponsiveness with bronchoconstriction, especially when inhaled.

Off-label low dose amitriptyline for insomnia disorder: Patient-reported outcomes.

PURPOSE: Low dose amitriptyline is prescribed off-label to improve sleep maintenance in patients with insomnia disorder. Data on treatment outcomes are limited. We aimed to assess patient-reported treatment effect and side effects of low dose amitriptyline for insomnia in routine care data. METHODS: Cross-sectional study: Seven hundred fifty-two consecutive patients with insomnia disorder having sleep maintenance problems were treated in an outpatient sleep clinic with low dose amitriptyline (10-20 mg based on self-titration). Treatment was intended to improve sleep maintenance. Before the planned follow-up consultation (approximately 6 weeks after start treatment) patients completed an online treatment evaluation questionnaire. Treatment (dose, adherence), sleep, fatigue, satisfaction and side effects were assessed by multiple-choice questions with room for free-text elaboration. RESULTS: 53.7% of the patients reported to use amitriptyline up to 10 mg/day, 42.9% used a self-increased dose of mostly 20 mg/day, while 3.5% had discontinued treatment. 73.9% of the total study population reported improvement of sleep maintenance, 31.3% improved sleep onset, 35.2% improved daytime fatigue, and 45.8% reported to be (very) satisfied with treatment results. 66.1% reported at least one side effect. The reported side effects were generally the already known side effects of amitriptyline. CONCLUSION: These patient-reported outcomes support the clinical observations that low dose amitriptyline improves sleep maintenance on the short term and that it is generally well tolerated. This further justifies randomized controlled trials in patients with insomnia disorder and sleep maintenance problems to assess the effectiveness and safety of low dose amitriptyline on the short and long term.

Does the addition of electrical stimulation or kinesiotherapy improve outcomes of amitriptyline treatment for women with vulvodynia? A randomized clinical trial.

INTRODUCTION AND HYPOTHESIS: Women diagnosed with provoked vulvodynia frequently report a great deal of frustration in achieving symptomatic relief. Physical therapy and drug treatment are among the interventions most indicated by guidelines; however, whether those modalities are effective when combined remains unclear. The objective was to evaluate the effectiveness of adding a physical therapy modality compared with amitriptyline alone for the treatment of vulvodynia. METHODS: Eighty-six women with vulvodynia were randomized to (G1) 25 mg amitriptyline, once a day (n=27), (G2) amitriptyline + electrical stimulation therapy (n=29) or (G3) amitriptyline + kinesiotherapy (n=30). All treatment modalities were administered for 8 weeks. The primary endpoint was the reduction in vestibular pain. Secondary measurements focused on sexual pain, frequency of vaginal intercourse, Friedrich score, and overall sexual function. Data were analyzed using intention-to-treat. RESULTS: All treatment modalities resulted in a significant decrease in vestibular pain (p<0.001), sexual pain (p<0.05), Friedrich score (p<0.001), and an increase in the frequency of sexual intercourse (p<0.05). G3 was more effective than G1 at reducing sexual pain (G1: 5.3±3.3 vs G3: 3.2±2.7; p=0.01) and at improving sexual function (G1: 18.8±9.8 vs G3: 23.9±7.8; p=0.04). CONCLUSION: Kinesiotherapy and electrotherapy additions to amitriptyline administration as well as amitriptyline alone, were effective at improving vestibular pain in women with vulvodynia. Women receiving physical therapy had the greatest improvement in sexual function and frequency of intercourse at post-treatment and follow-up.

Therapeutic potential of amitriptyline for paraquat-induced pulmonary fibrosis: Involvement of caveolin-1-mediated anti-epithelial-mesenchymal transition and inhibition of apoptosis.

OBJECTIVE: Treatment of pulmonary fibrosis caused by paraquat (PQ) poisoning remains problematic. Amitriptyline (AMT) has multiple pharmacological effects. Here we investigated the anti-fibrotic effect of AMT on PQ-induced pulmonary fibrosis and its possible mechanism. METHODS: C57BL/6 mice were randomly divided into control, PQ, PQ + AMT and AMT groups. Histopathology of the lungs, blood gas analysis, and levels of hydroxyproline (HYP), transforming growth factor ß1 (TGF-ß1) and interleukin 17 (IL-17) were measured. The siRNA transfection inhibited caveolin-1 in A549 cells, which induced epithelial-mesenchymal transition (EMT) by PQ and followed intervention with AMT. E-cadherin, N-cadherin, α-smooth muscle actin (α-SMA) and caveolin-1 were studied by immunohistochemistry and western blot analysis. The apoptosis rate was measured by flow cytometry. RESULTS: Compared with the PQ group, the PQ + AMT group displayed mild pathological changes in pulmonary fibrosis, lower HYP, IL-17 and TGF- ß1 levels in lung, but high TGF- ß1 in serum. Levels of N-cadherin and α-SMA in the lungs were significantly decreased, but caveolin-1 was increased, while SaO2 and PaO2 levels were higher. Compared with the PQ group, the apoptosis rate, N-cadherin and α-SMA levels in A549 cells were significantly decreased after PQ treatment and high dose AMT intervention (p < 0.01). The expressions of E-cadherin, N-cadherin and α-SMA in the PQ-induced cells transfected with caveolin-1 siRNA or siControl RNA were significantly different (p < 0.01), but the apoptosis rate was unaltered. CONCLUSION: AMT inhibited PQ-induced EMT in A549 cells and improved lung histopathology and oxygenation in mice by up-regulating caveolin-1.

Evaluation of adsorption performance and mechanisms of a highly effective 3D boron-doped graphene composite for amitriptyline pharmaceutical removal.

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.

European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention-part 1: amitriptyline.

OBJECTIVE: The aim of this paper is to critically re-appraise the published trials assessing amitriptyline for migraine prophylaxis. METHODS: We report our methods and results following the Preferred Reporting Items for Systematic Reviews (PRISMA), by searching MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials of pharmacologic treatments for migraine prophylaxis. We included randomized trials that compared amitriptyline with placebo for migraine prophylaxis in adults. Our outcomes of interest were informed by the Outcome Set for preventive intervention trials in chronic and episodic migraine (COSMIG) and include the proportion of patients who experience a 50% or more reduction in migraine days per month, migraine days per month, and adverse events leading to discontinuation. We assessed risk of bias by using a modified Cochrane RoB 2.0 tool and the certainty of evidence by using the GRADE approach. RESULTS: Our search yielded 10.826 unique records, of which three trials (n = 622) were eligible for data synthesis and analysis. We found moderate certainty evidence that amitriptyline increases the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo (relative risk: 1.60 (95% CI 1.17 to 2.19); absolute risk difference: 165 more per 1,000 (95% CI 47 more to 327 more). We found moderate certainty evidence that amitriptyline increases the proportion of patients who discontinue due to adverse events compared to placebo (risk difference: 0.05 (95% CI 0.01 to 0.10); absolute risk difference: 50 more per 1,000 (95% CI 10 more to 100 more). CONCLUSIONS: Our meta-analysis showed that amitriptyline may have a prophylactic role in migraine patients, however these results are far from robust. This warrants further large-scale research to evaluate the role of amitriptyline in migraine prevention.

Effect of an Antidepressant on Medication Adherence among Type 2 Diabetic Patients with Depression Accessing Care in GOPC of FETHI.

Comorbid depression among diabetes mellitus (DM) patients is on the increase. This has been linked with poor glycaemic control, greater risk of complications, high burden of medical cost and health care utilisation, and worsening prevalence of other comorbidities resulting in decreased life expectancy. This study determined the antidepressant effect of amitriptyline on depression and glycaemic control among the depressed type 2 DM patients attending Federal Teaching Hospital, Ido-Ekiti (FETHI), Nigeria. It was an interventional study involving 51 depressed type 2 DM patients randomly screened using Patient Health Questionnaire-9 (PHQ-9). They had health education and oral amitriptyline 50mg at night for two months. Postintervention assessment was done using the same tool. Respondents' age ranged between 44 and 78 years with a mean age of 58±8.4 years. Post-intervention assessment showed improved depressive symptoms; 50% of the respondents had significantly improved glycaemic control with a statistically significant effect on depression (the median score of PHQ-9 reduced from 6.0 to 3.0).

La dépression comorbide chez les diabétiques est en augmentation. Elle a été associée à un mauvais contrôle de la glycémie, à un risque accru de complications, à une charge élevée en termes de coûts médicaux et d'utilisation des soins de santé, ainsi qu'à un taux de mortalité plus élevé chez les personnes souffrant de comorbidité. Cette étude a déterminé l'effet de l'antidépresseur (Amitriptyline) sur la dépression et le contrôle de la glycémie chez les patients dépressifs atteints de diabète de type 2 qui fréquentent l'hôpital universitaire fédéral d'Ido-Ekiti (FETHI). Il s'agit d'une étude interventionnelle portant sur 51 patients atteints de diabète de type 2 et déprimés, sélectionnés au hasard à l'aide du questionnaire sur la santé des patients 9 (PHQ-9). Ils ont bénéficié d'une éducation à la santé et ont pris 50 mg d'amitriptyline par voie orale pendant deux mois. L'évaluation post-intervention a été réalisée à l'aide du même outil. L'âge des personnes interrogées était compris entre 44 et 78 ans, avec un âge moyen de 58± 8,4 ans. L'évaluation postintervention a montré une amélioration des symptômes dépressifs, 50% des personnes interrogées ont eu un contrôle glycémique significativement amélioré avec un effet statistiquement significatif sur la dépression (le score médian du PHQ est passé de 6,0 à 3,0). Mots clés: Diabète sucré, dépression, contrôle glycémique, observance thérapeutique.

Endothelial Acid Sphingomyelinase Promotes NLRP3 Inflammasome and Neointima Formation During Hypercholesterolemia.

The NOD-like receptor pyrin domain 3 (NLRP3) inflammasome is activated during atherogenesis, but how this occurs is unclear. Here, we explored the mechanisms activating and regulating NLRP3 inflammasomes via the acid sphingomyelinase (ASM)-ceramide signaling pathway. As a neointima formation model, partial left carotid ligations were performed on endothelial cell (EC)-specific ASM transgene mice (Smpd1trg/ECcre) and their control littermates (Smpd1trg/WT and WT/WT) fed on the Western diet (WD). We found neointima formation remarkably increased in Smpd1trg/ECcre mice over their control littermates. Next, we observed enhanced colocalization of NLRP3 versus adaptor protein ASC (the adaptor molecule apoptosis-associated speck-like protein containing a CARD) or caspase-1 in the carotid ECs of WD-treated Smpd1trg/ECcre mice but not in their control littermates. In addition, we used membrane raft (MR) marker flotillin-1 and found more aggregation of ASM and ceramide in the intima of Smpd1trg/ECcre mice than their control littermates. Moreover, we demonstrated by in situ dihydroethidium staining, carotid intimal superoxide levels were much higher in WD-treated Smpd1trg/ECcre mice than in their control littermates. Using ECs from Smpd1trg/ECcre and WT/WT mice, we showed ASM overexpression markedly enhanced 7-ketocholesterol (7-Ket)-induced increases in NLRP3 inflammasome formation, accompanied by enhanced caspase-1 activity and elevated interleukin-1ß levels. These 7-Ket-induced increases were significantly attenuated by ASM inhibitor amitriptyline. Furthermore, we determined that increased MR clustering with NADPH oxidase subunits to produce superoxide contributes to 7-Ket-induced NLRP3 inflammasome activation via a thioredoxin-interacting protein-mediated controlling mechanism. We conclude that ceramide from ASM plays a critical role in NLRP3 inflammasome activation during hypercholesterolemia via MR redox signaling platforms to produce superoxide, which leads to TXNIP dissociation.

Tantali fibromyalgic supplicium: Is there any relief with the antidepressant employment? A systematic review.

Widespread musculoskeletal pain characterizes fibromyalgia (FM), accompanied by sleep, fatigue, and mood problems. Chronic stress and depression play a crucial role in the etiology and pathophysiology of FM. They may contribute to a dysregulation of the central pain mechanisms together with the neuroendocrine and immune systems. Pharmacological treatments are the first-line therapy to reduce the symptoms of FM. The US Food and Drug Administration (FDA) indicated gabapentinoid, pregabalin, duloxetine, and milnacipran for adult patients. An alternative approach is widely used, based on therapies including interventions in patient education, behavioral therapy, exercise, pain management, and a healthy diet. A systematic search was performed on PubMed, MEDLINE, EMBASE, and Web of Science databases. The authors established the selection, inclusion, and exclusion criteria. We found a total of 908 articles. This systematic review will include ten articles selected after excluding duplicates and reading the abstracts and full texts. All studies related the effect of drugs to various symptoms caused by fibromyalgia patients with depression, such as insomnia/sleepiness, depression, suicide, difficulty walking/working, pain, fatigue, and nervousness. Although, we concluded that antidepressant drugs are effective in treating depression and pain in fibromyalgia, further studies are needed to understand the etiology of this disease and to find a combination of therapies to increase tolerability and adherence of the patient to the drug, decreasing the adverse effects.

Do medication prescription patterns follow guidelines in a cohort of women with interstitial cystitis/bladder pain syndrome?

OBJECTIVE: To describe prescription prevalence of oral bladder pain medications among women with interstitial cystitis/bladder pain syndrome (IC/BPS) and to compare with current treatment guidelines. METHODS: We sampled female patients with an ICD-9/10 diagnosis of IC/BPS (595.1/N30.10) by querying active users of the Veterans Health Administration. Medical records were reviewed to determine whether patients met IC/BPS diagnostic criteria. A cohort of women with other pelvic pain disorders was identified. Prescription prevalence of typical non-narcotic oral bladder pain medications was compared between the two groups and healthy controls. Prescription prevalence was also compared before and after the diagnosis of IC/BPS was made using Poisson regression. RESULTS: There were 641 women who met criteria for IC/BPS and 197 women with "Other pelvic pain" disorders. Women with IC/BPS were prescribed a pain medication more often than those with "Other pelvic pain" (77% vs. 59%, p < 0.0001). Of the women with IC/BPS, 44% tried three or more pain medications. Of women with a diagnosis of IC/BPS, only 67% were prescribed an American Urological Association-recommended medication. Prescription prevalence increased after diagnosis for both pentosan polysulfate (10%-29%, p < 0.0001) and hydroxyzine (17%-40%, p < 0.0001), but not for amitriptyline or cimetidine. Amitriptyline was prescribed to 223 women with IC/BPS, only 125 of which (56%) had a documented history of depression. CONCLUSIONS: Many women with IC/BPS required multiple bladder prescriptions, highlighting the difficulty in finding an effective treatment for IC/BPS. Pentosan polysulfate and hydroxyzine were preferred IC/BPS medications. Our next step will be to analyze treatment patterns in those patients who did not receive medications.

Real world use of oral treatments in interstitial cystitis/bladder pain syndrome in the UK: Outcome of a cross sectional study.

BACKGROUND: To describe the oral treatments people living with interstitial cystitis/bladder pain syndrome (IC/BPS) are using to treat their urologic condition in the UK. METHOD: A questionnaire hyperlink encompassing current and previous medications taken for IC/BPS with other sociodemographic and diagnostic indices was available to the Bladder Health UK website. Interested and fully consented individuals accessed and completed the survey. RESULTS: A total of 601 accessed the questionnaire of whom 173 participants responded (response rate: 28.7%) with a mean ± SD O'Leary/Sant scores of 20.12 ± 9.38. A sample size of 171 was estimated to be used in the survey. A fifth of the participants were not on any treatment at all. Amitriptyline was the most prevalent medication in use both alone and in combination. A shift in the use of unapproved (for IC/BPS) antidepressant, smooth muscle relaxant, opioids, gabapentenoids, and antibiotics was observed in the sample. There were no significant differences between the mean (SD) O'Leary/Sant scores of cohorts currently taking oral medications and those not taking it. More than two-thirds of the participants had been diagnosed with the disease more than 5 years. Just under a half (47.4%) of participants reported a history of allergy. CONCLUSION: Our study provides contemporary evidence that the treatments used for managing IC/BPS encompass a broad range of medications both recommended and not recommended by current guidelines. The latter suggests patients are willing to try novel treatments when more conventional ones are ineffective.