-
Clinical Therapeutics Mar 2024Treatments for myalgic encephalomyelitis and chronic fatigue syndrome can be adapted for post-COVID-19 condition. Our aim was to compare treatments in patients from our...
PURPOSE
Treatments for myalgic encephalomyelitis and chronic fatigue syndrome can be adapted for post-COVID-19 condition. Our aim was to compare treatments in patients from our post-COVID-19 clinic.
METHODS
We conducted a retrospective cohort study and included consecutive patients enrolled in our post-COVID-19 clinic. We included patients who received low-dose naltrexone, amitriptyline, duloxetine, and physical therapy, and evaluated improvements in fatigue, pain, dyspnea, and brain fog recorded in the electronic health record. We calculated the adjusted relative hazard of improvement using Cox proportional models. We adjusted for demographic characteristics, comorbidities, and prior COVID-19 hospitalization.
FINDINGS
We included the first 108 patients with post-COVID-19 enrolled in the clinic. Most of the patients received amitriptyline. The relative hazard of improvement for those taking low-dose naltrexone was 5.04 (95% CI, 1.22-20.77; P = 0.02) compared with physical therapy alone. Both fatigue and pain were improved in patients taking low-dose naltrexone; only fatigue was improved in patients taking amitriptyline.
IMPLICATIONS
Post-COVID-19 condition symptoms may improve in patients taking medications adapted from myalgic encephalomyelitis and chronic fatigue syndrome. Randomized controlled trials should evaluate these medications and translational studies should further evaluate their mechanisms of action.
Topics: Humans; Fatigue Syndrome, Chronic; Naltrexone; Retrospective Studies; Amitriptyline; COVID-19; Chronic Disease; Pain
PubMed: 38267326
DOI: 10.1016/j.clinthera.2023.12.009 -
Respiratory Research Oct 2023The standard therapy for bronchial asthma consists of combinations of acute (short-acting ß-sympathomimetics) and, depending on the severity of disease, additional...
INTRODUCTION
The standard therapy for bronchial asthma consists of combinations of acute (short-acting ß-sympathomimetics) and, depending on the severity of disease, additional long-term treatment (including inhaled glucocorticoids, long-acting ß-sympathomimetics, anticholinergics, anti-IL-4R antibodies). The antidepressant amitriptyline has been identified as a relevant down-regulator of immunological T2-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 (ß-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 T2-allergic phenotype and on acute airway hyperresponsiveness with bronchoconstriction, especially when inhaled.
Topics: Mice; Rats; Humans; Animals; Guinea Pigs; Bronchoconstriction; Methacholine Chloride; Amitriptyline; Histamine; Bronchodilator Agents; Serotonin; Acetylcholine; Sympathomimetics; 1-Methyl-3-isobutylxanthine; Dilatation; Lung; Asthma; Albuterol; Endothelins; Thromboxanes
PubMed: 37907918
DOI: 10.1186/s12931-023-02580-6 -
Toxicology in Vitro : An International... Mar 2023Paroxetine is functionally classified as a selective serotonin reuptake inhibitor. Paroxetine can induce mitochondria-dependent apoptosis through the ROS-MAPK...
INTRODUCTION
Paroxetine is functionally classified as a selective serotonin reuptake inhibitor. Paroxetine can induce mitochondria-dependent apoptosis through the ROS-MAPK pathway.Amitriptyline is a tricyclic antidepressant. This drug induces the expression of p53, thereby activating caspase-3. Amitriptyline has also been studied as a potential candidate for inducing oxidative stress and cytotoxicity in cancer cells, which may be more effective than other chemotherapy drugs. This study aims to to investigate the anticancer effects of paroxetine and amitriptyline and their combination treatment on HT29 and A549 cell lines for the first time.
METHODS
In order to investigate the anticancer effect of two drugs, paroxetine and amitriptyline, on inhibiting the growth of A549 and HT29 cancer cells, oxidative stress factors and LDH enzyme and apoptosis tests were performed.
RESULTS
Two drugs, amitriptyline and paroxetine alone, inhibited the growth of cancer cells in such a way that the inhibitory effect of the cells increased with the increase in the dose of the drug. In the simultaneous exposure of these two drugs, the inhibitory effect was much greater than the effect of single drug exposure. Also, these two drugs have caused LDH leakage and induction of apoptosis.
CONCLUSION
According to the results of the study, it was found that these two drugs have the necessary ability to inhibit the growth of cancer cells by inducing apoptosis and LDH leakage and inducing oxidative stress.
Topics: Humans; Paroxetine; Amitriptyline; A549 Cells; Selective Serotonin Reuptake Inhibitors; Antidepressive Agents, Tricyclic
PubMed: 36460226
DOI: 10.1016/j.tiv.2022.105532 -
Family Practice Apr 2017The role of amitriptyline in musculoskeletal pain is not as clearly defined as in classical neuropathic pain conditions. (Review)
Review
BACKGROUND
The role of amitriptyline in musculoskeletal pain is not as clearly defined as in classical neuropathic pain conditions.
OBJECTIVE
To assess the efficacy and effectiveness of amitriptyline in the treatment of pain in musculoskeletal complaints.
METHODS
An extensive search (including Medline, Embase and Web of Science) was made up to April 2016 for randomised controlled trials on amitriptyline in musculoskeletal complaints compared to placebo, usual care, or other analgesic use. Included studies were assessed for risk of bias. Outcomes of interest were pain reduction and function improvement.
RESULTS
Of the 2066 articles identified, seven were finally included. These studies were performed in patients with low back pain (4), rheumatoid arthritis (2), and patients with arm pain from repetitive use (1). No meta-analysis was performed due to clinical heterogeneity of the studies. Two studies with low risk of bias found positive results. One study found that 50 mg/day of amitriptyline [Visual Analogue Scale (VAS) -3.9 points] resulted in a significantly greater reduction in pain than treatment with pregabalin 600 mg/day (VAS -2.9 points) and improved function (improvement on the Oswestry Disability Index >20%: 65% versus 49.5%). Amitriptyline improved function in arm pain compared to placebo (Upper Extremity Function Scale: -3.9 versus 0.8). A similar amount of side-effects occurred in the amitriptyline and the comparison groups.
CONCLUSION
Few studies have evaluated the use of amitriptyline in musculoskeletal complaints. Although amitriptyline may be effective in musculoskeletal complaints, more studies are required to establish for whom amitriptyline works better than other analgesics.
Topics: Amitriptyline; Analgesics, Non-Narcotic; Arthritis, Rheumatoid; Humans; Low Back Pain; Musculoskeletal Pain; Pain Measurement
PubMed: 28334783
DOI: 10.1093/fampra/cmw134 -
The Journal of Family Practice Sep 2023YES. Low-dose naltrexone is as effective as amitriptyline in the treatment of painful diabetic neuropathy and has a superior safety profile (strength of recommendation... (Randomized Controlled Trial)
Randomized Controlled Trial
YES. Low-dose naltrexone is as effective as amitriptyline in the treatment of painful diabetic neuropathy and has a superior safety profile (strength of recommendation [SOR], B; single randomized controlled trial [RCT]). Low-dose naltrexone significantly reduced pain by 32% in inflammatory conditions and 44% in neuropathic conditions (SOR, B; single retrospective cohort study). Doses as low as 5.4 mg were found to reduce pain in 95% of patients with fibromyalgia (SOR, B; single prospective dose-response study).
Topics: Humans; Naltrexone; Pain Management; Amitriptyline; Fibromyalgia; Pain
PubMed: 37729143
DOI: 10.12788/jfp.0654 -
BMJ (Clinical Research Ed.) Apr 2023The studyTesfaye S, Sloan G, Petrie J, et al. Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine... (Randomized Controlled Trial)
Randomized Controlled Trial
The studyTesfaye S, Sloan G, Petrie J, et al. Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomised crossover trial. 2022;400:680-90.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/combination-therapy-for-painful-diabetic-neuropathy-is-safe-and-effective/.
Topics: Humans; Diabetic Neuropathies; Pregabalin; Analgesics; Amitriptyline; Duloxetine Hydrochloride; Treatment Outcome; Double-Blind Method; Diabetes Mellitus
PubMed: 37085164
DOI: 10.1136/bmj.p866 -
Expert Opinion on Pharmacotherapy Jul 2018Interstitial cystitis (IC) and bladder pain syndrome (BPS) are chronic conditions that can be debilitating for patients. There is no consensus as to their etiology, and... (Review)
Review
INTRODUCTION
Interstitial cystitis (IC) and bladder pain syndrome (BPS) are chronic conditions that can be debilitating for patients. There is no consensus as to their etiology, and there are many proposed treatment algorithms. Oftentimes multimodal therapy, such as combining behavioral modification and physical therapy alongside pharmacotherapies, will be utilized. With the various treatment options available to patients and providers, there is an ever-growing need to implement evidence-based therapies.
AREAS COVERED
The authors explore the different pharmacotherapies as commonly recommended in the American Urological Association (AUA) and European Association of Urology (EAU) multitiered guidelines for IC/BPS treatment as well as other investigational therapies. Pharmacotherapies targeting bladder, pelvic, and/or systemic factors in the overall treatment of IC/BPS are discussed with a particular focus on evidence-based guideline therapies. This article also looks at emerging therapies of interest.
EXPERT OPINION
IC/BPS is a syndrome that requires a multimodal approach, including clinical phenotyping and directed therapy based on the patient's symptoms. The AUA and EAU provide guidelines for practitioners to follow, but adequate treatment requires the therapy to be targeted toward the patient's phenotypic domain.
Topics: Amitriptyline; Antibodies, Monoclonal; Antidepressive Agents, Tricyclic; Cimetidine; Cystitis, Interstitial; Histamine Antagonists; Humans; Hydroxyzine; Immunosuppressive Agents; Pentosan Sulfuric Polyester
PubMed: 29972328
DOI: 10.1080/14656566.2018.1491968 -
Annals of Emergency Medicine May 2017
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Brugada Syndrome; Drug Overdose; Electrocardiography; Humans; Male; Middle Aged; Suicide, Attempted; Tachycardia, Sinus; Unconsciousness
PubMed: 28442081
DOI: 10.1016/j.annemergmed.2016.03.022 -
Anesthesia and Analgesia Jun 2018
Topics: Amitriptyline; Animals; Cardiotoxicity; Guinea Pigs; Lipids
PubMed: 29517570
DOI: 10.1213/ANE.0000000000002884 -
American Journal of Men's Health Mar 2018Amitriptyline is an old drug but is still prevalently used as the first-line treatment for a variety of common diseases. Surprisingly, knowledge of sexual risks with... (Meta-Analysis)
Meta-Analysis Review
Amitriptyline is an old drug but is still prevalently used as the first-line treatment for a variety of common diseases. Surprisingly, knowledge of sexual risks with amitriptyline comes from only one clinical trial and several case reports from three decades ago. In the current study, a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) related to amitriptyline and sexual dysfunction (SD) was performed. The frequency, gender-difference, types, disease-specificity and time course of SD, and the relationship between SD and nonsexual adversity were studied. A total of 14 publications, including 8 qualified randomized clinical trials, were eligible. The frequency of SD in overall, male and female patients was 5.7, 11.9 and 1.7%, respectively. SD was six-fold higher in men than women. The frequency of SD was 6.9% in depressive patients compared with 0.8% in non-depressive patients ( p = .008), and gradually decreased at 8 weeks after treatment ( p = .02). Amitriptyline impacted arousal and libido more than orgasm and ejaculation in male patients but mainly libido in female patients. SD was significantly correlated with insomnia linearly whereas somnolence and nausea dually. Therefore, amitriptyline-associated SD mainly occurs in depressive and male patients, disturbs each phase of the sexual response cycle in men but mainly libido in women, gradually decreases under long-term treatment, and can be predicted by the co-existence of insomnia, somnolence or nausea during treatment. Clinicians should caution and tailor the gender and disease vulnerability of amitriptyline in their practice.
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Depression; Humans; Male; Sexual Dysfunctions, Psychological
PubMed: 29019272
DOI: 10.1177/1557988317734519