-
Pediatric Emergency Care Dec 2021Amitriptyline ingestion is an important cause of poisoning morbidity and mortality in Turkey and other countries. In contrast to adults, data concerning amitriptyline...
BACKGROUND
Amitriptyline ingestion is an important cause of poisoning morbidity and mortality in Turkey and other countries. In contrast to adults, data concerning amitriptyline intoxication in children are limited. The purpose of this study was to investigate amitriptyline intoxication findings in the pediatric population, based on age groups and reported dosages.
METHODS
The medical records of 192 patients admitted to the Karadeniz Technical University Medical Faculty Farabi Hospital Pediatric Emergency Department, Turkey, due to amitriptyline intoxication in 1997-2017 were examined retrospectively. Patients were divided into 6 groups based on amitriptyline doses and 4 groups based on age. Complete blood count, blood glucose, serum electrolytes, renal and liver function tests, coagulation tests (prothrombin time and partial thromboplastin time), and blood gas analysis were studied in all patients. Electrocardiography was performed on all children, and chest radiography and electroencephalography on those with respiratory or central nervous system symptoms.
RESULTS
Amitriptyline intoxication was most frequently observed between the ages of 1 and 4 years. The most common signs and symptoms observed at time of hospital admission were lethargy and drowsiness (45.3%), sinus tachycardia (19.2%), and nausea and vomiting (13%). The most common laboratory finding was hyperglycemia (17.7). Six patients were intubated because of respiratory failure, and mechanical ventilation was initiated in these cases. One patient with amitriptyline overdose had persistent supraventricular tachycardia. Four children died due to amitriptyline intoxication.
CONCLUSIONS
Tricyclic antidepressant intoxication is a leading cause of mortality and morbidity in children. It is therefore particularly important to identify the clinical and laboratory findings that develop with high-dose consumption.
Topics: Adult; Amitriptyline; Antidepressive Agents, Tricyclic; Child; Child, Preschool; Humans; Infant; Retrospective Studies; Tertiary Care Centers; Turkey
PubMed: 32150000
DOI: 10.1097/PEC.0000000000002055 -
Biomolecules Nov 2022SARS-CoV-2 has undergone mutations, yielding clinically relevant variants.
BACKGROUND
SARS-CoV-2 has undergone mutations, yielding clinically relevant variants.
HYPOTHESIS
We hypothesized that in SARS-CoV-2, two highly conserved Orf3a and E channels directly related to the virus replication were a target for the detection and inhibition of the viral replication, independent of the variant, using FDA-approved ion channel modulators.
METHODS
A combination of a fluorescence potassium ion assay with channel modulators was developed to detect SARS-CoV-2 Orf3a/E channel activity. Two FDA-approved drugs, amantadine (an antiviral) and amitriptyline (an antidepressant), which are ion channel blockers, were tested as to whether they inhibited Orf3a/E channel activity in isolated virus variants and in nasal swab samples from COVID-19 patients. The variants were confirmed by PCR sequencing.
RESULTS
In isolated SARS-CoV-2 Alpha, Beta, and Delta variants, the channel activity of Orf3a/E was detected and inhibited by emodin and gliclazide (IC = 0.42 mM). In the Delta swab samples, amitriptyline and amantadine inhibited the channel activity of viral proteins, with IC values of 0.73 mM and 1.11 mM, respectively. In the Omicron swab samples, amitriptyline inhibited the channel activity, with an IC of 0.76 mM.
CONCLUSIONS
We developed an efficient method to screen FDA-approved ion channel modulators that could be repurposed to detect and inhibit SARS-CoV-2 viral replication, independent of variants.
Topics: Humans; Amantadine; Amitriptyline; Ion Channels; SARS-CoV-2; Drug Evaluation, Preclinical; Drug Repositioning; COVID-19 Drug Treatment
PubMed: 36421688
DOI: 10.3390/biom12111673 -
The American Journal of Emergency... Nov 2015
Topics: Adult; Amitriptyline; Antipsychotic Agents; Carbamazepine; Colitis, Ischemic; Humans; Male; Oxcarbazepine; Quetiapine Fumarate
PubMed: 25886897
DOI: 10.1016/j.ajem.2015.03.038 -
International Journal of Molecular... Dec 2022The facilitated activity of N-methyl-D-aspartate receptors (NMDARs) in the central and peripheral nervous systems promotes neuropathic pain. Amitriptyline (ATL) and...
The facilitated activity of N-methyl-D-aspartate receptors (NMDARs) in the central and peripheral nervous systems promotes neuropathic pain. Amitriptyline (ATL) and desipramine (DES) are tricyclic antidepressants (TCAs) whose anti-NMDAR properties contribute to their analgetic effects. At therapeutic concentrations <1 µM, these medicines inhibit NMDARs by enhancing their calcium-dependent desensitization (CDD). Li+, which suppresses the sodium−calcium exchanger (NCX) and enhances NMDAR CDD, also exhibits analgesia. Here, the effects of different [Li+]s on TCA inhibition of currents through native NMDARs in rat cortical neurons recorded by the patch-clamp technique were investigated. We demonstrated that the therapeutic [Li+]s of 0.5−1 mM cause an increase in ATL and DES IC50s of ~10 folds and ~4 folds, respectively, for the Ca2+-dependent NMDAR inhibition. The Ca2+-resistant component of NMDAR inhibition by TCAs, the open-channel block, was not affected by Li+. In agreement, clomipramine providing exclusively the NMDAR open-channel block is not sensitive to Li+. This Ca2+-dependent interplay between Li+, ATL, and DES could be determined by their competition for the same molecular target. Thus, submillimolar [Li+]s may weaken ATL and DES effects during combined therapy. The data suggest that Li+, ATL, and DES can enhance NMDAR CDD through NCX inhibition. This ability implies a drug−drug or ion−drug interaction when these medicines are used together therapeutically.
Topics: Rats; Animals; Antidepressive Agents, Tricyclic; Amitriptyline; Receptors, N-Methyl-D-Aspartate; Lithium; Calcium; Desipramine; Calcium, Dietary
PubMed: 36555818
DOI: 10.3390/ijms232416177 -
European Journal of Neurology Jan 2024Little is known about the comparative effects of migraine preventive drugs. We aimed to estimate treatment retention and effectiveness of migraine preventive drugs in a...
BACKGROUND AND PURPOSE
Little is known about the comparative effects of migraine preventive drugs. We aimed to estimate treatment retention and effectiveness of migraine preventive drugs in a nationwide registry-based cohort study in Norway between 2010 and 2020.
METHODS
We assessed retention, defined as the number of uninterrupted treatment days, and effectiveness, defined as the reduction in filled triptan prescriptions during four 90-day periods after the first preventive prescription, compared to a 90-day baseline period. We compared retention and efficacy for different drugs against beta blockers. Comparative retention was estimated with hazard ratios (HRs), adjusted for covariates, using Cox regression, and effectiveness as odds ratios (ORs) using logistic regression, with propensity-weighted adjustment for covariates.
RESULTS
We identified 104,072 migraine patients, 81,890 of whom were female (78.69%) and whose mean (standard deviation) age was 44.60 (15.61) years. Compared to beta blockers, botulinum toxin (HR 0.43, 95% confidence interval [CI] 0.42-0.44) and calcitonin gene-related peptide pathway antibodies (CGRPabs; HR 0.63, 95% CI 0.59-0.66) were the least likely to be discontinued, while clonidine (HR 2.95, 95% CI 2.88-3.02) and topiramate (HR 1.34, 95% CI 1.31-1.37) were the most likely to be discontinued. Patients on simvastatin, CGRPabs, and amitriptyline were more likely to achieve a clinically significant reduction in triptan use during the first 90 days of treatment, with propensity score-adjusted ORs of 1.28 (95% CI 1.19-1.38), 1.23 (95% CI 0.79-1.90), and 1.13 (95% CI 1.08-1.17), respectively.
CONCLUSIONS
We found a favorable effect of CGRPabs, amitriptyline, and simvastatin compared with beta blockers, while topiramate and clonidine were associated with poorer outcomes.
Topics: Humans; Female; Adult; Male; Topiramate; Cohort Studies; Clonidine; Amitriptyline; Migraine Disorders; Registries; Tryptamines; Simvastatin
PubMed: 37754544
DOI: 10.1111/ene.16062 -
European Journal of Clinical... Sep 2023We evaluated in vitro activity of 13 drugs used in the treatment of some non-communicable diseases via repurposing to determine their potential use in the treatment of...
Synergistic combination of carvedilol, amlodipine, amitriptyline, and antibiotics as an alternative treatment approach for the susceptible and multidrug-resistant A. baumannii infections via drug repurposing.
We evaluated in vitro activity of 13 drugs used in the treatment of some non-communicable diseases via repurposing to determine their potential use in the treatment of Acinetobacter baumannii infections caused by susceptible and multidrug-resistant strains. A. baumannii is a multidrug-resistant Gram-negative bacteria causing nosocomial infections, especially in intensive care units. It has been identified in the WHO critical pathogen list and this emphasises urgent need for new treatment options. As the development of new therapeutics is expensive and time consuming, finding new uses of existing drugs via drug repositioning has been favoured. Antimicrobial susceptibility tests were conducted on all 13 drugs according to CLSI. Drugs with MIC values below 128 μg/mL and control antibiotics were further subjected to synergetic effect and bacterial time-kill analysis. Carvedilol-gentamicin (FICI 0.2813) and carvedilol-amlodipine (FICI 0.5625) were determined to have synergetic and additive effect, respectively, on the susceptible A. baumannii strain, and amlodipine-tetracycline (FICI 0.75) and amitriptyline-tetracycline (FICI 0.75) to have additive effect on the multidrug-resistant A. baumannii strain. Most remarkably, both amlodipine and amitriptyline reduced the MIC of multidrug-resistant, including some carbapenems, A. baumannii reference antibiotic tetracycline from 2 to 0.5 μg/mL, for 4-folds. All these results were further supported by bacterial time-kill assay and all combinations showed bactericidal activity, at certain hours, at 4XMIC. Combinations proposed in this study may provide treatment options for both susceptible and multidrug-resistant A. baumannii infections but requires further pharmacokinetics and pharmacodynamics analyses and in vivo re-evaluations using appropriate models.
Topics: Humans; Anti-Bacterial Agents; Drug Repositioning; Amitriptyline; Carvedilol; Amlodipine; Drug Synergism; Microbial Sensitivity Tests; Acinetobacter Infections; Drug Resistance, Multiple, Bacterial; Tetracyclines; Acinetobacter baumannii
PubMed: 37428238
DOI: 10.1007/s10096-023-04634-5 -
Journal of Gastroenterology and... Apr 2022Amitriptyline improves symptoms in functional abdominal pain disorders (FAPD) in adults with variable results in pediatric studies. The study aims to evaluate the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIM
Amitriptyline improves symptoms in functional abdominal pain disorders (FAPD) in adults with variable results in pediatric studies. The study aims to evaluate the efficacy of amitriptyline in pediatric FAPD.
METHODS
In this open-label trial, children (≤ 18 years) diagnosed as FAPD based on ROME IV criteria were randomized to amitriptyline or placebo for 12 weeks. Post-treatment improvement of pain and quality of life (QOL) from the baseline were compared between the two groups.
RESULTS
The mean age of 149 children (amitriptyline 75, placebo 74) was 11.3 ± 3.5 years (79 boys). There was a significant difference in pain improvement in terms of reduction in scores for intensity (3.4 vs 0.9), frequency (3.6 vs 0.6), duration (3.5 vs 0.9), and QOL (2.3 vs 0.9) between amitriptyline and placebo group (P < 0.001 in all). Responders (> 50% reduction) in pain was seen in 76% in amitriptyline compared with 14.9% in the placebo group (P < 0.001). On multivariate analysis, the use of amitriptyline was the only factor predictive of response (odds ratio 24.1, 95% confidence interval: 9.1-64.6, P < 0.001). Minor adverse events were comparable between the groups (25.3% vs 13.5%, respectively, P = 0.07). Eighty-nine percent of children (24/27) who had extended treatment duration (6.8 ± 1.8 months) had pain improvement. After discontinuation of amitriptyline, 70% had sustained response over a mean follow up of 15.84 ± 5.6 months.
CONCLUSIONS
A 3-month trial of amitriptyline gives sustained relief of pain in two-thirds of children with FAPD. The safety profile of the drug and its efficacy necessitate more frequent use in the clinical settings.
Topics: Abdominal Pain; Adult; Aged, 80 and over; Amitriptyline; Child; Double-Blind Method; Humans; Irritable Bowel Syndrome; Male; Quality of Life; Treatment Outcome
PubMed: 34935191
DOI: 10.1111/jgh.15765 -
Clinical Journal of Sport Medicine :... Sep 2020To estimate the direct costs of pediatric postconcussive syndrome (PCS).
OBJECTIVE
To estimate the direct costs of pediatric postconcussive syndrome (PCS).
DESIGN
Retrospective cohort study.
SETTING
Subspecialty sports medicine clinics of a large pediatric tertiary care network in the United States.
PATIENTS
One hundred fifty-four patients aged 5 to 18 years with PCS, evaluated between 2010 and 2011.
ASSESSMENT OF INDEPENDENT VARIABLES
Direct costs included visits to sports medicine clinic, visio-vestibular therapy, homebound education, subspecialist referral, and prescription-only medications (amantadine and amitriptyline), all measured beginning at 28 days after injury.
MAIN OUTCOME MEASURES
Postconcussive syndrome was defined as persistence beyond 28 days from injury.
RESULTS
The cost incurred by each PCS patient for sports medicine visits was $1575, for visio-vestibular therapy was $985, for homebound tutoring was $55, for prescription medications was $22, and for subspecialist referral was $120, totaling $3557 per patient, with a 95% confidence interval range of $2886 to $4257.
CONCLUSIONS
Given the high economic costs of PCS determined in this study, therapies that mitigate this syndrome may have the potential to be cost-effective and even cost saving.
Topics: Adolescent; Amantadine; Amitriptyline; Child; Child, Preschool; Confidence Intervals; Direct Service Costs; Education; Humans; Outcome Assessment, Health Care; Post-Concussion Syndrome; Referral and Consultation; Retrospective Studies; Sports Medicine; Time Factors; United States
PubMed: 31219930
DOI: 10.1097/JSM.0000000000000732 -
Neurological Sciences : Official... May 2024
Topics: Humans; Amitriptyline; Rosacea; Exanthema
PubMed: 38221540
DOI: 10.1007/s10072-024-07307-z -
Pharmacoepidemiology and Drug Safety Apr 2023Low dose amitriptyline is prescribed off-label to improve sleep maintenance in patients with insomnia disorder. Data on treatment outcomes are limited. We aimed to...
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.
Topics: Humans; Amitriptyline; Sleep Initiation and Maintenance Disorders; Off-Label Use; Cross-Sectional Studies; Treatment Outcome; Fatigue; Patient Reported Outcome Measures
PubMed: 36309966
DOI: 10.1002/pds.5561