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Polski Merkuriusz Lekarski : Organ... 2023Aim: Conduct a comparative analysis of effectiveness of obesity treatment in primary care using patient-oriented approach with motivational counseling for lifestyle...
COMPARATIVE ANALYSIS OF EFFECTIVENESS OF OBESITY TREATMENT IN PRIMARY CARE USING PATIENT-ORIENTED APPROACH WITH MOTIVATIONAL COUNSELING FOR LIFESTYLE CORRECTION AND ITS COMBINATION WITH ARMODAFINIL THERAPY IN PATIENTS WITH CONCOMITANT SHIFT WORK SLEEP DISORDER.
OBJECTIVE
Aim: Conduct a comparative analysis of effectiveness of obesity treatment in primary care using patient-oriented approach with motivational counseling for lifestyle correction and its combination with armodafinil therapy in patients with concomitant shift work sleep disorder.
PATIENTS AND METHODS
Materials and Methods: 75 patients with obesity were studied, 38 patients had shift work disorder. Patients were divided into 2 groups: I (37 patients with obesity treated with motivational counseling) and II (38 patients with obesity and shift work disorder treated additionally with armodafinil 150 mg daily). The examination was at baseline, after 1st, 3th and 6th months. Statistical analysis was provided.
RESULTS
Results: After 1 month of treatment, there were improvement of eating behavior, level of anxiety and depression, prognosis of diabetes development. At 3rd month, more pronounced changes were observed in 2nd group: 10% body weight loss, changes in eating behavior, sleep quality, anxiety level (p<0.05). After 6 months, examined indicators in both groups normalized, but dynamics in 2nd group was more significant; armodafinil-treated group had significantly better results in body weight loss, BMI, WC, HC, ConI, AVI, BPs, HOMA index, serotonin, leptin, levels of anxiety and depression, eating behavior, daytime dysfunction, level of sleepiness, quality of life and risk of developing diabetes.
CONCLUSION
Conclusions: The use of armofafinil in addition to patientoriented motivational counseling in lifestyle correction ("5 As" and "5R") in patients with obesity connected with shift work disorder and excessive daytime sleepiness allows to reduce body weight by more than 16,52%, in contrast to isolated use of the same technique of motivational counseling in obese patients without sleep disorder (only 5,51%).
Topics: Humans; Modafinil; Sleep Disorders, Circadian Rhythm; Quality of Life; Benzhydryl Compounds; Life Style; Obesity; Diabetes Mellitus; Weight Loss; Primary Health Care; Counseling
PubMed: 38069857
DOI: 10.36740/Merkur202305115 -
International Journal of Molecular... Nov 2023-CE-123, a novel dopamine transporter inhibitor, has emerged as a potential candidate for cognitive enhancement. The objective of this study was to compare the tissue...
-CE-123, a novel dopamine transporter inhibitor, has emerged as a potential candidate for cognitive enhancement. The objective of this study was to compare the tissue distribution profiles, with a specific focus on central nervous system distribution and metabolism, of -CE-123 and -modafinil. To address this objective, a precise liquid chromatography-high resolution mass spectrometry method was developed and partially validated. Neuropharmacokinetic parameters were assessed using the Combinatory Mapping Approach. Our findings reveal distinct differences between the two compounds. Notably, -CE-123 demonstrates a significantly superior extent of transport across the blood-brain barrier (BBB), with an unbound brain-to-plasma concentration ratio (K) of 0.5, compared to -modafinil's K of 0.1. A similar pattern was observed for the transport across the blood-spinal cord barrier. Concerning the drug transport across cellular membranes, we observed that -CE-123 primarily localizes in the brain interstitial space, whereas -modafinil distributes more evenly across both sides of the plasma membrane of the brain's parenchymal cells (K). Furthermore, our study highlights the substantial differences in hepatic metabolic stability, with -CE-123 having a 9.3-fold faster metabolism compared to -modafinil. In summary, the combination of improved BBB transport and higher affinity of -CE-123 to dopamine transporters in comparison to -modafinil makes -CE-123 a promising candidate for further testing for the treatment of cognitive decline.
Topics: Benzhydryl Compounds; Brain; Central Nervous System; Dopamine Plasma Membrane Transport Proteins; Modafinil
PubMed: 38069277
DOI: 10.3390/ijms242316956 -
Environmental Science and Pollution... Jan 2024Nonmedical use of modafinil (MOD) led to increased rates of overdose toxicity, road accidents, addiction, withdrawal, suicide, and mental illnesses. The current study...
Selenium alleviates modafinil-induced neurobehavioral toxicity in rat via PI3K/Akt/mTOR/GSK3B signaling pathway and suppression of oxidative stress and apoptosis: in vivo and in silico study.
Nonmedical use of modafinil (MOD) led to increased rates of overdose toxicity, road accidents, addiction, withdrawal, suicide, and mental illnesses. The current study aims to determine the probable MOD brain toxicity and elucidate the possible role of selenium (Se) in ameliorating the neurotoxicity in rat models. Fifty-four male Albino rats were randomly assigned into nine groups. The groups were G1 (control negative), G2 (Se0.1), G3 (Se0.2), G4 (MOD300), G5 (MOD600), G6 (Se0.1 + MOD300), G7 (Se0.2 + MOD300), G8 (Se0.1 + MOD600), and G9 (Se0.2 + MOD600). After finishing the experiment, blood and brain tissue were harvested for biochemical and histological investigation. Neurobehavior parameters were assessed. Tissue neurotransmitter levels and oxidative stress markers were assessed. Gene expression of PI3K/Akt/mTOR-GSK3B, orexin, and orexin receptor2 was measured by qRT-PCR. Histological and immunohistochemistry assessments, as well as molecular docking, were carried out. MOD-induced neurobehavioral toxicity exhibited by behavioral and cognitive function impairments, which are associated with decreased antioxidant activities, increased MDA levels, and decreases in neurotransmitter levels. Brain levels of mRNA expression of PI3K, Akt, and mTOR were decreased, while GS3K, orexin, and orexin receptors were significantly elevated. These disturbances were confirmed by histopathological brain changes with increased silver and Bax immunostaining and decreased crystal violet levels. MOD induced neurotoxic effects in a dose-dependent manner. Compared with the MOD groups, SE coadministration significantly attenuates MOD-induced toxic changes. Docking study shows the protective role of Se as an apoptosis inhibitor and inflammation inhibitor. In conclusion, Se could be used as a biologically effective antioxidant compound to protect from MOD neurobehavioral toxicity in Wistar rats by reversing behavioral alterations, inflammation, apoptosis, and oxidative injury.
Topics: Humans; Rats; Male; Animals; Selenium; Proto-Oncogene Proteins c-akt; Antioxidants; Phosphatidylinositol 3-Kinases; Modafinil; Orexins; Molecular Docking Simulation; Rats, Wistar; Signal Transduction; TOR Serine-Threonine Kinases; Oxidative Stress; Inflammation; Apoptosis; Neurotransmitter Agents; Glycogen Synthase Kinase 3 beta
PubMed: 38015391
DOI: 10.1007/s11356-023-31093-4 -
Physical Medicine and Rehabilitation... Feb 2024Pharmacologic treatment of disorders of consciousness remains a critical but challenging task for clinicians. Amantadine has been shown to promote the rate of neurologic... (Review)
Review
Pharmacologic treatment of disorders of consciousness remains a critical but challenging task for clinicians. Amantadine has been shown to promote the rate of neurologic recovery for patients with traumatic disorders of consciousness when administered between 4 and 16 weeks, as demonstrated by a well-designed randomized control trial. While there are no large, randomized controlled trials to support the use of other dopaminergic medicines (bromocriptine, levodopa, apomorphine), there is a large body of literature implicating their role in improving alertness and responsiveness in disorders of consciousness. Zolpidem can increase the level of consciousness in a small subset of patients. Zolpidem and intrathecal baclofen likely increase the level of consciousness via the mesocircuit pathway. Psychostimulant medications can be initiated in patients, even without strong evidence to support their use, as long as basic principles of brain injury medicine are followed, and there are systems in place to evaluate therapeutic response.
Topics: Humans; Consciousness; Zolpidem; Consciousness Disorders; Brain Injuries; Amantadine; Randomized Controlled Trials as Topic
PubMed: 37993186
DOI: 10.1016/j.pmr.2023.06.023 -
Clinical NeuropharmacologyAcute traumatic brain injury is one of the most common causes of death and disability. Reduction in the level of consciousness is a significant complication that can...
OBJECTIVES
Acute traumatic brain injury is one of the most common causes of death and disability. Reduction in the level of consciousness is a significant complication that can impact morbidity. Glasgow Coma Scale (GCS) is the most widely used method of assessing the level of consciousness. Neurostimulants such as amantadine and modafinil are common pharmacologic agents that increase GCS in patients with brain trauma. This study aimed to compare the effectiveness of these 2 drugs.
METHODS
This systematic review obtained articles from Google Scholar, PubMed, Scopus, Embase, and MEDLINE databases. Extensive searches were conducted separately by 4 individuals in 3 stages. Ultimately, 16 clinical trials, cohort studies, case reports, and case series articles were obtained after reading the title, abstract, and full text and considering the exclusion criteria. The data of the final article were entered into the analysis table. This study was registered with PROSPERO (registration number CRD42022334409) and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
Amantadine seems to be associated with a higher overall response rate. In contrast, modafinil is associated with the most remarkable change in GCS score during treatment. However, the number of clinical trials with high quality and sample size has not been satisfactory to compare the effectiveness of these 2 drugs and their potential side effects.
CONCLUSIONS
The authors recommend additional double-blind clinical trials are needed to be conducted with a larger sample size, comparing amantadine with modafinil to delineate the efficacy and adverse effects, both short and long term.
Topics: Humans; Modafinil; Consciousness; Brain Injuries, Traumatic; Amantadine; Brain Injuries; Randomized Controlled Trials as Topic
PubMed: 37962310
DOI: 10.1097/WNF.0000000000000577 -
Scientific Reports Nov 2023The use of so-called 'smart drugs' such as modafinil to improve cognitive performance has recently attracted considerable attention. However, their side effects have... (Randomized Controlled Trial)
Randomized Controlled Trial
The use of so-called 'smart drugs' such as modafinil to improve cognitive performance has recently attracted considerable attention. However, their side effects have limited user enthusiasm. Open-label placebo (OLP) treatment, i.e., inert treatments that are openly disclosed to individuals as having no active pharmacological ingredient, has been shown to improve various medical symptoms and conditions, including those related to cognitive performance. OLP treatment could therefore be an exciting alternative to pharmacological cognitive enhancers. Here, we used a randomized-controlled design to investigate the effect of a 21-day OLP treatment on several sub-domains of cognitive performance in N = 78 healthy volunteers. Subjective and objective measures of cognitive performance as well as different measures of well-being were obtained before and after the treatment period. Using a combination of classic Frequentist and Bayesian analysis approaches showed no additional benefit from OLP treatment in any of the subjective or objective measures of cognitive performance. Our study thus highlights possible limitations of OLP treatment in boosting cognitive performance in healthy volunteers. These findings are discussed in the light of expectancy-value considerations that may determine OLP efficacy.
Topics: Humans; Attention; Bayes Theorem; Cognition; Healthy Volunteers; Modafinil; Placebo Effect
PubMed: 37945662
DOI: 10.1038/s41598-023-45979-3 -
Purinergic Signalling Nov 2023Adenosine receptor (AR) suppresses inflammation and fibrosis by activating cyclic adenosine monophosphate (cAMP) signaling. We investigated whether altered AR expression...
Adenosine receptor (AR) suppresses inflammation and fibrosis by activating cyclic adenosine monophosphate (cAMP) signaling. We investigated whether altered AR expression contributes to the development of fibrotic diseases and whether AAR and AAR upregulation inhibits fibrotic responses. Primary human lung fibroblasts (HLFs) from normal (NHLFs) or patients with idiopathic pulmonary fibrosis (DHLF) were used for in vitro testing. Murine models of fibrotic liver or pulmonary disease were developed by injecting thioacetamide intraperitoneally, by feeding a high-fat diet, or by intratracheal instillation of bleomycin. Modafinil, which activates cAMP signaling via AAR and AAR, was administered orally. The protein amounts of AAR, AAR, and exchange protein directly activated by cAMP (Epac) were reduced, while collagen and α-smooth muscle actin (α-SMA) were elevated in DHLFs compared to NHLFs. In liver or lung tissue from murine models of fibrotic diseases, AAR and AAR were downregulated, but AAR and AAR were not. Epac amounts decreased, and amounts of collagen, α-SMA, K2.3, and K3.1 increased compared to the control. Modafinil restored the amounts of AAR, AAR, and Epac, and reduced collagen, α-SMA, K2.3, and K3.1 in murine models of fibrotic diseases. Transforming growth factor-β reduced the amounts of AAR, AAR, and Epac, and elevated collagen, α-SMA, K2.3, and K3.1 in NHLFs; however, these alterations were inhibited by modafinil. Our investigation revealed that AAR and AAR downregulation induced liver and lung fibrotic diseases while upregulation attenuated fibrotic responses, suggesting that AAR and AAR-upregulating agents, such as modafinil, may serve as novel therapies for fibrotic diseases.
PubMed: 37938538
DOI: 10.1007/s11302-023-09973-8 -
Journal of Clinical Sleep Medicine :... Mar 2024This case report recounts the details of a patient diagnosed with narcolepsy and cataplexy whose headaches improved once treatment with armodafinil began. The clinical...
UNLABELLED
This case report recounts the details of a patient diagnosed with narcolepsy and cataplexy whose headaches improved once treatment with armodafinil began. The clinical significance of this report lies in the fact that armodafinil is known to cause headaches, at least initially. But perhaps through a reduced need for caffeine and/or a regulation of sleep/wake, armodafinil may reduce headache frequency and severity.
CITATION
Barone DA. Headache improves with armodafinil. 2024;20(3):469-470.
Topics: Humans; Modafinil; Narcolepsy; Caffeine; Cataplexy; Headache
PubMed: 37921201
DOI: 10.5664/jcsm.10906 -
Cureus Sep 2023Our aim is to report the clinical profile and outcome of patients diagnosed with idiopathic hypersomnia (IH). Idiopathic hypersomnolence is a complex, debilitating, and...
Our aim is to report the clinical profile and outcome of patients diagnosed with idiopathic hypersomnia (IH). Idiopathic hypersomnolence is a complex, debilitating, and uncommon sleep disorder manifested mainly by chronic excessive daytime sleepiness (EDS). This paper reports on the treatment of a patient with idiopathic hypersomnia who was treated with low sodium oxybate (LXB) due to a lack of response to the first-line drug modafinil. This patient, who presented with worsening excessive daytime sleepiness, sleep drunkenness, and sleep disturbances, was diagnosed with idiopathic hypersomnia by overnight polysomnography (PSG) and a multiple sleep latency test (MSLT). Stimulant agent modafinil was prescribed along with sleep hygiene education. Her symptoms did not respond to modafinil, and she was switched to a recently approved newer medication, i.e., low sodium oxybate.
PubMed: 37900508
DOI: 10.7759/cureus.45976