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American Journal of Ophthalmology Case... Dec 2023To present a case of irreversible corneal edema after 10 years of amantadine use. A literature review was carried out to describe the clinical characteristics and...
PURPOSE
To present a case of irreversible corneal edema after 10 years of amantadine use. A literature review was carried out to describe the clinical characteristics and outcomes of amantadine-induced corneal edema.
OBSERVATIONS
A 36-year-old woman presented with a 6-week history of gradually progressive bilateral painless visual loss with visual acuity (VA) of 20/350 and 20/300 in the right and left eye, respectively. Examination showed bilateral diffuse central corneal edema with multiple Descemet membrane folds without endothelial guttata, keratic precipitates or intraocular inflammation. This did not respond to hypertonic saline drops and empirical treatment for presumed herpetic endotheliitis with oral acyclovir. Medication review revealed the use of amantadine 100mg daily for the past 10 years, prescribed by her neurologist for fatigue. Despite discontinuing amantadine, corneal edema was irreversible due to a markedly reduced endothelial cell count of 625 (right) and 680 cells/mm (left).
CONCLUSIONS AND IMPORTANCE
This case highlights the need to consider amantadine as a cause of unexplained bilateral non-guttae corneal edema. A literature review of 33 case reports revealed broadly similar features of amantadine-induced corneal edema; whilst most cases had favorable outcomes with median VA 20/25 (interquartile range IQR 20/20-20/30) and complete resolution of corneal edema within 30 days (IQR 14-35) of amantadine discontinuation, most experienced low endothelial cell density 759 cells/mm (IQR 621-1078). Taken together, screening specular microscopy ought to be considered for those in whom amantadine is likely required long-term.
PubMed: 37840541
DOI: 10.1016/j.ajoc.2023.101881 -
BMJ Open Jan 2024Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), and effective treatments are lacking. Amantadine is one of the most used treatments, although...
Amantadine and/or transcranial magnetic stimulation for fatigue associated with multiple sclerosis (FETEM): study protocol for a phase 3 randomised, double-blind, cross-over, controlled clinical trial.
INTRODUCTION
Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), and effective treatments are lacking. Amantadine is one of the most used treatments, although its efficacy is under debate. Transcranial magnetic stimulation (TMS) is a promising intervention that has shown positive effects in some preliminary investigations. We aim to investigate the effect of 6 weeks of amantadine and/or TMS in fatigue due to MS.
METHODS AND ANALYSIS
The study is a national, multicentre, phase 3, randomised, double-blind, cross-over, placebo-controlled and sham-controlled clinical trial. Adult patients with relapsing-remitting MS, Expanded Disability Status Scale score of 1.5-4.5 and Fatigue Severity Score>4 are eligible for the trial. Participants will be randomised to one of the sequences of the study. Each sequence consists of four periods of 6 weeks of treatment and three washout periods of 12-18 weeks. All patients will receive all the combinations of therapies. The primary outcome is the Modified Fatigue Impact Scale. The secondary outcomes are the Symbol Digit Modalities Test (cognition), Beck Depression Inventory-II (depressive symptoms) and Short-Survey 12 (quality of life). Safety and cost-effectiveness will also be evaluated. An exploratory substudy including MRI and blood biomarkers will be conducted.
ETHICS AND DISSEMINATION
The study is approved by the Ethics Committee of the Hospital Clinico San Carlos and the Spanish Agency of Medications and Medical Devices. All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences.
TRIAL REGISTRATION NUMBER
EudraCT 2021-004868-95; NCT05809414.
Topics: Adult; Humans; Multiple Sclerosis; Transcranial Magnetic Stimulation; Quality of Life; Amantadine; Double-Blind Method; Fatigue; Treatment Outcome; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Clinical Trials, Phase III as Topic
PubMed: 38176857
DOI: 10.1136/bmjopen-2023-078661 -
Alzheimer's Research & Therapy Aug 2023There are few updated studies on the prevalence and management of Alzheimer's disease (AD), which could be underdiagnosed or undertreated. The COVID-19 pandemic may have...
BACKGROUND
There are few updated studies on the prevalence and management of Alzheimer's disease (AD), which could be underdiagnosed or undertreated. The COVID-19 pandemic may have worsened the deficiencies in the diagnosis and treatment of these patients. Electronic medical records (EMR) offer an opportunity to assess the impact and management of medical processes and contingencies in the population.
OBJECTIVE
To estimate AD prevalence in Spain over a 6-year period, based on treated patients, according to usual clinical practice. Additionally, to describe the management of AD-treated patients and the evolution of that treatment during the 2020 COVID-19 pandemic.
METHODS
Retrospective study using the Spanish IQVIA EMR database. Patients treated with donepezil, galantamine, rivastigmine, and/or memantine were included in the study. Annual AD prevalence (2015-2020) was estimated and extrapolated to the national population level. Most frequent treatments and involved specialties were described. To assess the effect of COVID-19, the incidence of new AD cases in 2020 was calculated and compared with newly diagnosed cases in 2019.
RESULTS
Crude AD prevalence (2015-2020) was estimated at 760.5 per 100,000 inhabitants, and age-standardized prevalence (2020) was 664.6 (male 595.7, female 711.0). Monotherapy was the most frequent way to treat AD (86.2%), in comparison with dual therapy (13.8%); rivastigmine was the most prescribed treatment (37.3%), followed by memantine (36.4%) and donepezil (33.0%). Rivastigmine was also the most utilized medication in newly treated patients (46.7%), followed by donepezil (29.8%), although donepezil persistence was longer (22.5 vs. 20.6 months). Overall, donepezil 10 mg, rivastigmine 9.5 mg, and memantine 20 mg were the most prescribed presentations. The incidence rate of AD decreased from 148.1/100,000 (95% confidence interval [CI] 147.0-149.2) in 2019 to 118.4/100,000 (95% CI 117.5-119.4) in 2020.
CONCLUSIONS
The obtained prevalence of AD-treated patients was consistent with previous face-to-face studies. In contrast with previous studies, rivastigmine, rather than donepezil, was the most frequent treatment. A decrease in the incidence of AD-treated patients was observed during 2020 in comparison with 2019, presumably due to the significant impact of the COVID-19 pandemic on both diagnosis and treatment. EMR databases emerge as valuable tools to monitor in real time the incidence and management of medical conditions in the population, as well as to assess the health impact of global contingencies and interventions.
Topics: Humans; Male; Female; Alzheimer Disease; Donepezil; Rivastigmine; Memantine; Cholinesterase Inhibitors; Retrospective Studies; Pandemics; Prevalence; Piperidines; Phenylcarbamates; Indans; COVID-19; Galantamine
PubMed: 37537656
DOI: 10.1186/s13195-023-01271-0 -
Acta Pharmaceutica Sinica. B Feb 2024A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8 T cells is subject to the regulatory T lymphocytes...
A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8 T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated -cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile -carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and lung metastasis suppression with the aid of PD-1 antibody.
PubMed: 38322349
DOI: 10.1016/j.apsb.2023.10.006 -
Journal of Enzyme Inhibition and... Dec 2023An important drug used in the treatment of Parkinson's disease is amantadine. We are the first to perform a comprehensive study based on various glycation and oxidation...
An important drug used in the treatment of Parkinson's disease is amantadine. We are the first to perform a comprehensive study based on various glycation and oxidation factors, determining the impact of amantadine on protein glycoxidation. Sugars (glucose, fructose, galactose) and aldehydes (glyoxal, methylglyoxal) were used as glycation agents, and chloramine T was used as an oxidant. Glycoxidation biomarkers in albumin treated with amantadine were generally not different from the control group (glycation/oxidation factors), indicating that the drug did not affect oxidation and glycation processes. Molecular docking analysis did not reveal strong binding sites of amantadine on the bovine serum albumin structure. Although amantadine poorly scavenged hydroxyl radical and hydrogen peroxide, it had significantly lower antioxidant and antiglycation effect than all protein oxidation and glycation inhibitors. In some cases, amantadine even demonstrated glycoxidant, proglycation, and prooxidant properties. In summary, amantadine exhibited weak antioxidant properties and a lack of antiglycation activity.
Topics: Antioxidants; Glycation End Products, Advanced; Molecular Docking Simulation; Serum Albumin, Bovine; Amantadine
PubMed: 36325591
DOI: 10.1080/14756366.2022.2137161 -
Clinical Parkinsonism & Related... 2023Data on Huntington's disease (HD) epidemiology, treatment patterns, and economic burden in Israel are scarce.
INTRODUCTION
Data on Huntington's disease (HD) epidemiology, treatment patterns, and economic burden in Israel are scarce.
METHODS
Annual prevalence and incidence of HD (ICD-9-CM 333.4) were assessed in the Israel-based Maccabi Healthcare Services (MHS) database 2016-2018. Adherence (medication possession rate [MPR], proportion of disease covered) were assessed for adult people with HD (PwHD) 2013-2018. Healthcare resources utilization (HCRU) and costs related to inpatient and outpatient visits and all medications in 2018 were assessed for PwHD, who were randomly matched to MHS members without HD (1:3) by birth-year and sex.
RESULTS
Overall, 164 patients had at least one HD diagnosis. Annual prevalence and incidence were 4.45 and 0.24/100,000, respectively. A total of 67.0% of adult patients (n = 106) were taking tetrabenazine (median MPR and proportion of disease covered, 74.3% and 30.2%, respectively), 65.1% benzodiazepines (75.8% and 32.3%), and 11.3% amantadine (79.2% and 6.0%). Over a 1-year follow-up, PwHD (n = 81) had significantly more neurologist, psychiatrist, physiotherapist, and speech therapist visits (P < 0.05 for each) and more hospitalization days (P < 0.0001) compared with matched controls (n = 243). Total healthcare and medication costs per patient (US dollars) were significantly higher for PwHD than controls ($7,343 vs. $3,625; P < 0.001).
DISCUSSION/CONCLUSION
PwHD have greater annual HCRU and medical costs than MHS members without HD in Israel. Among those who have taken medications, adherence was lower than 80% (both MPR and proportion of disease covered), which may translate into suboptimal symptom relief and quality of life.
PubMed: 37497383
DOI: 10.1016/j.prdoa.2023.100208 -
Case Reports in Psychiatry 2023Tardive dyskinesia (TD) is characterized by abnormal and involuntary movements that generally occur after prolonged exposure to neuroleptic medications. In this article,...
Tardive dyskinesia (TD) is characterized by abnormal and involuntary movements that generally occur after prolonged exposure to neuroleptic medications. In this article, we present the case of a 29-year-old man with schizophrenia who developed TD following treatment with haloperidol. Despite various attempts with benzodiazepines, amantadine, and anticholinergics, the dyskinesias persisted. However, after 2 years of treatment with olanzapine alone, a progressive improvement occurred, leading to the complete disappearance of the dyskinesias. We also provide a brief review of reported cases of antipsychotic-induced TD that has improved with olanzapine.
PubMed: 37908858
DOI: 10.1155/2023/6688623 -
Journal of Feline Medicine and Surgery May 2024Chronic 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... (Review)
Review
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.
Topics: Cats; Animals; Neuralgia; Cat Diseases; Pain Management; Analgesics; Combined Modality Therapy
PubMed: 38710218
DOI: 10.1177/1098612X241246518 -
Clinics and Practice Jul 2023The usual adverse events of amantadine are dizziness, dry mouth, and peripheral edema. Postmarketing experience has revealed abnormal movements such as tremors,...
The usual adverse events of amantadine are dizziness, dry mouth, and peripheral edema. Postmarketing experience has revealed abnormal movements such as tremors, involuntary muscle contractions, and gait abnormalities. Herein, we report a case of an elderly male who presented with generalized twitching associated with amantadine. A 64-year-old male presenting with jerking movements within one day of onset was admitted. Sudden and involuntary distal lower and upper limb muscle twitching was observed. The subject presented subsequent brief movements when attempting to stand or hold arms antigravity. He was diagnosed with Parkinson's disease three years ago. Eight days before the presentation to the emergency department, he consulted with his primary care physician, who prescribed amantadine to improve his motor symptoms. On the seventh day, he developed brisk abnormal movements. Laboratory exams, neuroimaging, and electroencephalogram were unremarkable. Amantadine was discontinued. After three days, the patient reported that his jerking movements had fully recovered. To the authors' knowledge, 22 individuals with amantadine-associated myoclonus had already been reported in the literature. The pathophysiology of amantadine-induced myoclonus is probably related to serotoninergic pathways. Myoclonus secondary to amantadine was slightly more common in men. The population affected was elderly, with a mean and median age of 67.7 and 64 years.
PubMed: 37489424
DOI: 10.3390/clinpract13040075 -
Medicine Jun 2023Amantadine hydrochloride is a risky drug for triggering delirium in dialysis patients; however, it is often administered casually. Furthermore, little is known regarding...
Amantadine hydrochloride is a risky drug for triggering delirium in dialysis patients; however, it is often administered casually. Furthermore, little is known regarding the recovery and prognosis of dialysis patients with amantadine-associated delirium. Data of this retrospective cohort study were collected from a local hospital database for hospitalizations between January 2011 and December 2020. Patients were divided into 2 cohorts: early recovery (recovery within 14 days) and delayed recovery (recovery more than 14 days). The cases were analyzed together with the intermonth temperature using descriptive statistics. A Kaplan-Meier survival curve and binary logistic regression were applied for the analyses of prognoses and factors. A total of 57 patients were included in this study. The most common symptoms were hallucinations (45.61%) and muscle tremors (43.86%). Early recovery was observed in 63.16% of the patients. Only 3.51% of the cases occurred in local summer (June, July, and August). Better prognoses for survival (hazard ratio [HR] = 0.066, 95% confidence interval [95% CI] = 0.021-0.212) and hospitalization costs (7968.42 ± 3438.43 CNY vs 12852.38 ± 9361.13 CNY, P = .031) were observed in patients with early recovery than in those with delayed recovery. In the multivariate logistic regression adjusted by 1:1 propensity score matching, delayed recovery was independently caused by insomnia (P = .022, = 10.119, 95% CI = 1.403-72.990) and avoided in patients with urine volume over 300 mL (P = .029, = 0.018, 95% CI = 0.006-0.621). The increment (per 100 mg) of cumulative dose (P = .190, = 1.588, 95% CI = 0.395-3.172) tended to be a risk of delayed recovery. The area under curve of the receiver operating characteristic curve was 0.867, with a sensitivity of 90.5% and a specificity of 82.4% at the cutoff point (cutoff = 0.432). For amantadine-associated delirium in dialysis patients with uneven seasonal distribution, early recovery with better prognosis should be the aim of treatment by giving priority to the remedy of insomnia.
Topics: Humans; Renal Dialysis; Retrospective Studies; Seasons; Sleep Initiation and Maintenance Disorders; Amantadine; Delirium
PubMed: 37390288
DOI: 10.1097/MD.0000000000034077