-
Sleep Medicine Nov 2023Insomnia is a modifiable risk factor for suicide often treated with medications. However, little is known about the associations between insomnia medications and risk of...
PURPOSE
Insomnia is a modifiable risk factor for suicide often treated with medications. However, little is known about the associations between insomnia medications and risk of death by suicide. The purpose of this study is to model the comparative risk of suicide by each insomnia medication compared to zolpidem, a sedative-hypnotic approved for insomnia.
METHODS
First prescription fills of medications commonly used to treat insomnia were identified in electronic medical records. Date and cause of death were identified in death certificates. Cox proportional hazards models were used to analyze time from insomnia prescription to suicide.
RESULTS
More than 2 million patients filled a new insomnia prescription between 2005 and 2015, and 518 of them died by suicide within 12 months. Compared to zolpidem, the tricyclic antidepressants (amitriptyline, doxepin) were associated with a 64% lower risk of suicide (HR 0.36 (95% CI 0.22-0.66) and the sedating antihistamines (hydroxyzine, diphenhydramine) a 40% lower risk of suicide (HR 0.60 (0.41-0.89)). In contrast, the tetracyclic antidepressant (mirtazapine) was associated with a 62% higher risk of suicide (HR 1.62 (95% CI 1.10-2.38) compared to zolpidem.
CONCLUSION
Insomnia is a modifiable risk factor for suicide, yet many medications used to treat insomnia have never been tested for the indication in clinical trials. To define efficacy in the prevention of suicide, trials are warranted.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Zolpidem; Suicide; Antidepressive Agents; Hypnotics and Sedatives
PubMed: 37801864
DOI: 10.1016/j.sleep.2023.08.016 -
European Urology Open Science Oct 2023Radiotherapy of the pelvis is a widely used method for the treatment of malignancies, and local complications including pain following pelvic radiation therapy are... (Review)
Review
The Benefits and Harms of Pharmacological Treatment for Postradiation Pelvic Pain: A Systematic Review by the European Association of Urology Chronic Pelvic Pain Panel with Recommendations for Clinical Practice.
CONTEXT
Radiotherapy of the pelvis is a widely used method for the treatment of malignancies, and local complications including pain following pelvic radiation therapy are acknowledged complications.
OBJECTIVE
The primary objective is to assess the clinical effectiveness and safety of pharmacological therapies on postradiation pelvic pain.
EVIDENCE ACQUISITION
A systematic review of the use of different pharmacological treatments in the management of post-radiation pelvic pain was conducted (PROSPERO-ID: CRD42021249026). Comprehensive searches of EMBASE, Medline, and Cochrane library were performed for publications between January 1980 and April 2021. The primary outcomes were improvement in pain and adverse events following treatment. The secondary outcomes included quality of life, bowel function, and urinary function.
EVIDENCE SYNTHESIS
After screening 1514 abstracts, four randomised controlled trials were identified, enrolling 355 patients with bladder and anorectal subtypes of postradiotherapy chronic pelvic pain (CPP). A narrative synthesis was performed as heterogeneity of included studies precluded a meta-analysis. A single study reported a significant reduction in pain after 6 mo in patients with bladder pain syndrome treated with hyaluronic acid or hyperbaric oxygen. Anorectal pain was reported to be reduced by the application of 4% formalin, but the use of hyperbaric oxygen in postradiotherapy anorectal pain remains controversial. Adverse event reporting was generally poor. Studies looking at medications used routinely in guidelines for neuropathic pain, such as gabapentin, pregabalin, amitriptyline, and duloxetine, were absent or of poor quality when it came to postradiation pelvic pain.
CONCLUSIONS
Beneficial effects of hyperbaric oxygen or formalin on pain, quality of life, and functional symptoms were seen in patients with certain CPP subtypes, but the current evidence level is too weak to allow recommendations about the use of any pharmacological treatment for postradiation pelvic pain.
PATIENT SUMMARY
Different pharmacological treatments are used to treat pain after radiotherapy, but current studies are of insufficient quality to determine whether these should be recommended and many chronic pelvic pain subtypes are not covered. Further research is needed.
PubMed: 37711669
DOI: 10.1016/j.euros.2023.08.009 -
Neurotherapeutics : the Journal of the... Jan 2024While loss-of-function (LoF) variants in KCNQ2 are associated with a spectrum of neonatal-onset epilepsies, gain-of-function (GoF) variants cause a more complex...
While loss-of-function (LoF) variants in KCNQ2 are associated with a spectrum of neonatal-onset epilepsies, gain-of-function (GoF) variants cause a more complex phenotype that precludes neonatal-onset epilepsy. In the present work, the clinical features of three patients carrying a de novo KCNQ2 Y141N (n = 1) or G239S variant (n = 2) respectively, are described. All three patients had a mild global developmental delay, with prominent language deficits, and strong activation of interictal epileptic activity during sleep. Epileptic seizures were not reported. The absence of neonatal seizures suggested a GoF effect and prompted functional testing of the variants. In vitro whole-cell patch-clamp electrophysiological experiments in Chinese Hamster Ovary cells transiently-transfected with the cDNAs encoding Kv7.2 subunits carrying the Y141N or G239S variants in homomeric or heteromeric configurations with Kv7.2 subunits, revealed that currents from channels incorporating mutant subunits displayed increased current densities and hyperpolarizing shifts of about 10 mV in activation gating; both these functional features are consistent with an in vitro GoF phenotype. The antidepressant drug amitriptyline induced a reversible and concentration-dependent inhibition of current carried by Kv7.2 Y141N and G239S mutant channels. Based on in vitro results, amitriptyline was prescribed in one patient (G239S), prompting a significant improvement in motor, verbal, social, sensory and adaptive behavior skillsduring the two-year-treatment period. Thus, our results suggest that KCNQ2 GoF variants Y141N and G239S cause a mild DD with prominent language deficits in the absence of neonatal seizures and that treatment with the Kv7 channel blocker amitriptyline might represent a potential targeted treatment for patients with KCNQ2 GoF variants.
Topics: Infant, Newborn; Cricetinae; Animals; Humans; Amitriptyline; Cricetulus; CHO Cells; Gain of Function Mutation; Epilepsy; Phenotype; Seizures; KCNQ2 Potassium Channel
PubMed: 38241158
DOI: 10.1016/j.neurot.2023.10.006 -
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 -
Neurological Sciences : Official... May 2024
Topics: Humans; Amitriptyline; Rosacea; Exanthema
PubMed: 38221540
DOI: 10.1007/s10072-024-07307-z -
Bioinformation 2024Neuropathic pain largely influences the well-being of patients. Anticonvulsant and antidepressant medications, such as Pregabalin, Gabapentin, and Amitriptyline, are...
Neuropathic pain largely influences the well-being of patients. Anticonvulsant and antidepressant medications, such as Pregabalin, Gabapentin, and Amitriptyline, are routinely prescribed as initial treatments for neuropathic pain. The study sample has a total of 270 patients who meet the inclusion criteria and are further distributed into three equally sized groups (A, B, and C). Group A was administered with Gabapentine 300mg, Group B with Pregabalin 75 mg, and Amitriptyline 10 mg to Group C. The occurrence of any adverse drug response was documented using the ADR reporting form, while the pain of the patient's post-medication was recorded using a numerical pain rating scale (NPRS). The comparison of the NPRS scores of all three groups "by using ANOVA test" both at baseline and after 15 days reveal that the differences between the three groups are statistically insignificant (p > 0.089). However, after one month of continuous use, the difference becomes slightly significant (I.e., p = 0.003). Gabapentin, pregabalin, and amitriptyline demonstrate similar effectiveness in alleviating neuropathic (NeP) pain. The study concludes that gabapentin is superior to both pregabalin and amitriptyline with fewer adverse effects, leading to improved patient adherence for long-term use.
PubMed: 38854766
DOI: 10.6026/973206300200386 -
Frontiers in Pain Research (Lausanne,... 2023Standard medical therapy (SMT) in children with functional abdominal pain disorders (FAPD) includes cyproheptadine and amitriptyline. While percutaneous electrical nerve...
INTRODUCTION
Standard medical therapy (SMT) in children with functional abdominal pain disorders (FAPD) includes cyproheptadine and amitriptyline. While percutaneous electrical nerve field stimulation (PENFS) has shown benefit, no study has compared outcomes of PENFS to SMT. We aimed to examine changes in abdominal pain, nausea and disability before and after treatment and compare outcomes between treatments.
METHODS
The records of FAPD patients ages 11-21 years, treated with 4 weeks of PENFS, cyproheptadine or amitriptyline were reviewed. Outcomes were evaluated using validated questionnaires [Abdominal Pain Index (API), Nausea Severity Scale (NSS), and the Functional Disability Inventory (FDI)] at baseline and follow-up within 3 months (FU).
RESULT
Of 101 patients, 48% received PENFS, 31% cyproheptadine and 21% received amitriptyline. Median ages were 17 (15-19), 16 (15-18) and 15 (11-16) years respectively and the majority were females (75%, 90% and 52% respectively). In the PENFS group, API ( = 0.001), NSS ( = 0.059) and FDI ( = 0.048) were significantly lower at FU. API ( = 0.034) but not NSS and FDI ( > 0.05) decreased significantly at FU in the amitriptyline group. API, NSS and FDI did not change significantly with cyproheptadine at FU ( > 0.05). FU API scores were lower in PENFS vs. cyproheptadine ( = 0.04) but not vs. amitriptyline ( = 0.64). The FDI scores were significantly lower in the amitriptyline vs. cyproheptadine group ( = 0.03).
CONCLUSION
Therapy with PENFS showed improvements in abdominal pain, nausea and disability while amitriptyline showed improvements in abdominal pain within 3 months of treatment. PENFS was more effective than cyproheptadine in improving abdominal pain. Amitriptyline improved disability scores more than cyproheptadine and showed promise for treatment. PENFS may be a good non-pharmacologic alternative for FAPD.
PubMed: 37795388
DOI: 10.3389/fpain.2023.1251932 -
Canadian Family Physician Medecin de... Apr 2024To provide a summary of the noteworthy medical articles published in 2023 that are relevant to family physicians. (Review)
Review
OBJECTIVE
To provide a summary of the noteworthy medical articles published in 2023 that are relevant to family physicians.
SELECTING THE EVIDENCE
Articles were chosen and ranked by the PEER (Patients, Experience, Evidence, Research) team, a group of primary care health professionals focused on evidence-based medicine. The selection process involved routine surveillance of tables of contents in high-impact medical journals and continuous monitoring of EvidenceAlerts. Articles were prioritized based on their direct applicability to and potential to influence primary care practice.
MAIN MESSAGE
Selected articles addressed various clinical areas of primary care. The topics included a comparison of a treat-to-target approach versus a high-intensity statins prescription for lipid management; semaglutide and its impact on cardiovascular outcomes; respiratory syncytial virus vaccine for older adults; chlorthalidone versus hydrochlorothiazide in preventing cardiovascular events; amitriptyline for irritable bowel syndrome; the role of opioids in acute back pain; safety of oral penicillin challenges in patients allergic to penicillin; spironolactone for facial acne; strategies to reverse frailty in older adults; and identifying the provider of chronic disease management. Two "up and coming" medications are also mentioned: retatrutide for weight loss and fezolinetant for vasomotor symptoms of menopause.
CONCLUSION
Research published in 2023 yielded several high-quality articles with topics relevant to primary care, including cardiovascular care, irritable bowel syndrome, care of the elderly, and acne management.
Topics: Female; Humans; Aged; Irritable Bowel Syndrome; Analgesics, Opioid; Primary Health Care; Penicillins; Acne Vulgaris
PubMed: 38626998
DOI: 10.46747/cfp.7004245 -
Environmental Science and Pollution... Mar 2024The uptake, translocation, and metabolization of four widely used drugs, amitriptyline, orphenadrine, lidocaine, and tramadol, were investigated in a laboratory study....
The uptake, translocation, and metabolization of four widely used drugs, amitriptyline, orphenadrine, lidocaine, and tramadol, were investigated in a laboratory study. Cress (Lepidium sativum L.) and pea (Pisum sativum L.) were employed as model plants. These plants were grown in tap water containing the selected pharmaceuticals at concentrations ranging from 0.010 to 10 mg L, whereby the latter concentration was employed for the (tentative) identification of drug-related metabolites formed within the plant. Thereby, mainly phase I metabolites were detected. Time-resolved uptake studies, with sampling after 1, 2, 4, 8, and 16 days, revealed that all four pharmaceuticals were taken up by the roots and further relocated to plant stem and leaves. Also in these studies, the corresponding phase I metabolites could be detected, and their translocation from root to stem (pea only) and finally leaves could be investigated.
Topics: Amitriptyline; Pisum sativum; Brassicaceae; Orphenadrine; Tramadol; Lidocaine; Plants; Vegetables; Pharmaceutical Preparations; Plant Roots
PubMed: 38363510
DOI: 10.1007/s11356-024-32379-x