Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.323
Filtrar
2.
Cochrane Database Syst Rev ; 5: CD012714, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34031871

RESUMO

BACKGROUND: Idiopathic hypersomnia is a disorder of excessive daytime sleepiness, often accompanied by long sleep times or pronounced difficulty in awakening, in the absence of a known cause. The optimal treatment strategy for idiopathic hypersomnia is currently unknown. OBJECTIVES: To assess the effects of medications for daytime sleepiness and related symptoms in individuals with idiopathic hypersomnia and, in particular, whether medications may: 1. reduce subjective measures of sleepiness; 2. reduce objective measures of sleepiness; 3. reduce symptoms of cognitive dysfunction; 4. improve quality of life; and 5. be associated with adverse events. SEARCH METHODS: We searched the following databases on 4 February 2021: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 1 February 2021), and reference lists of articles. CRS Web includes randomized or quasi-randomized controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialized registers of Cochrane Review Groups, including the Cochrane Epilepsy Group. We previously searched the WHO ICTRP separately when loading of ICTRP records into CRS Web was temporarily suspended. SELECTION CRITERIA: Randomized studies comparing any medication to placebo, another medication, or a behavioral intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional data. We collected data on adverse events from the included trials. MAIN RESULTS: We included three trials, with a total of 112 participants. Risk of bias was low for the included studies. Two pharmaceutical company-sponsored trials compared modafinil with placebo, involving 102 participants, nearly all of whom had idiopathic hypersomnia without long sleep time. Modafinil significantly improved self-reported sleepiness on the Epworth Sleepiness Scale by 5.08 points more than placebo (95% confidence interval (CI) 3.01 to 7.16; 2 studies, 101 participants; high-certainty evidence). Modafinil also significantly improved disease severity on the Clinical Global Impression of Severity scale by 1.02 points (95% CI 0.11 to 1.93; 1 study, 30 participants; moderate-certainty evidence) and resulted in a greater proportion of participants who were "much improved" or "very much improved" on the Clinical Global Impression of Change (odds ratio (OR) for improvement 5.14, 95% CI 1.76 to 15.00; 1 study, 70 participants; moderate-certainty evidence). Ability to remain awake on the Maintenance of Wakefulness Test was significantly improved with modafinil, by 4.74 minutes more than with placebo (95% CI 2.46 to 7.01; 2 studies, 99 participants; high-certainty evidence). Ratings of exhaustion and effectiveness/performance were improved with modafinil compared to placebo in one study. Number of naps per week was no different between modafinil and placebo across two studies. Participants receiving modafinil experienced more side effects, although the difference did not reach statistical significance (OR 1.68, 95% CI 0.28 to 9.94; 2 studies, 102 participants; low-certainty evidence). One trial studying 20 participants with different disorders of sleepiness included 10 participants with idiopathic hypersomnia, with or without long sleep time, and compared clarithromycin to placebo. We only included the subset of trial data for those participants with idiopathic hypersomnia, per our protocol. There were no significant differences between clarithromycin and placebo for the Epworth Sleepiness Scale, psychomotor vigilance testing, sleep inertia, other subjective ratings, or side effects. AUTHORS' CONCLUSIONS: Modafinil is effective for the treatment of several aspects of idiopathic hypersomnia symptomatology, based on studies predominantly including participants with idiopathic hypersomnia without long sleep times, with low risk of bias, and evidence certainty ranging from high to low. There is insufficient evidence to conclude whether clarithromycin is effective for the treatment of idiopathic hypersomnia. There is a clear need for additional studies testing interventions for the treatment of idiopathic hypersomnia.


Assuntos
Claritromicina/uso terapêutico , Distúrbios do Sono por Sonolência Excessiva/tratamento farmacológico , Hipersonia Idiopática/complicações , Modafinila/uso terapêutico , Promotores da Vigília/uso terapêutico , Viés , Distúrbios do Sono por Sonolência Excessiva/etiologia , Humanos , Placebos/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Vigília
3.
BMJ Case Rep ; 14(3)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753384

RESUMO

Many patients with chronic fatigue syndrome (CFS) fail to derive benefit from evidence-based treatments such as cognitive-behavioural therapy (CBT) and graded exercise therapy leading to permanent disability. To discover whether a repeat prescription of modafinil might potentiate the benefits of CBT leading to social recovery as defined by 2 or more point improvement in energy and muscular pain/concentration and return to work or full-time training. Three patients with treatment-resistant CFS (mean duration 17.66 years) treated with modafinil and CBT in a Liaison Psychiatry clinic were retrospectively reviewed. Progress was reviewed at baseline, 4-6 months and 10-24 months. Patients rated their fatigue, pain and concentration using 10-point Likert scales. 2/3 achieved clinically meaningful improvements in energy and pain/concentration and 3/3 achieved social recovery. Modafinil, when prescribed over the medium term, would appear to be a potentially useful potentiating agent when added to CBT.


Assuntos
Terapia Cognitivo-Comportamental , Síndrome de Fadiga Crônica , Síndrome de Fadiga Crônica/tratamento farmacológico , Humanos , Modafinila , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
4.
Aerosp Med Hum Perform ; 92(3): 190-200, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33754977

RESUMO

INTRODUCTION: Fatigue is a common problem in aviation. The identification of efficacious fatigue countermeasures is crucial for sustaining flight performance during fatigue-inducing operations. Stimulants are not recommended for consistent use, but are often implemented during flight operations with a high risk of fatigue. As such, it is important to evaluate the efficacy of approved stimulants for sustaining flight performance, alertness, and mood.METHODS: Four electronic databases (PubMed, PsycInfo, SPORTDiscus, Web of Science) were systematically searched to identify research on the effects of caffeine, dextroamphetamine, and modafinil during simulated or in-flight operations.RESULTS: There were 12 studies identified that assessed the effects of at least 1 stimulant. Overall, dextroamphetamine and modafinil were effective for sustaining flight performance and pilot mood during extended wakefulness. Results with caffeine were inconsistent.DISCUSSION: Dextroamphetamine and modafinil appear to sustain flight performance and mood during extended wakefulness. However, most studies have used flight simulators and short operation durations. Additional research is needed in realistic settings and during longer duration operations. Caffeines effects were inconsistent across studies, possibly due to differences in study methodology or individual caffeine responses. Despite fatigue being a common problem in civilian aviation as well, only one study in this review included civil aviators. More research should be conducted on the effects of caffeine during civil operations.CONCLUSION: Dextroamphetamine and modafinil appear to be effective fatigue countermeasures but should be further evaluated in more ecologically valid settings. The effects of caffeine are unclear at this time and should continue to be evaluated.Ehlert AM, Wilson PB. Stimulant use as a fatigue countermeasure in aviation. Aerosp Med Hum Perform. 2021; 92(3):190200.


Assuntos
Medicina Aeroespacial , Aviação , Estimulantes do Sistema Nervoso Central , Estimulantes do Sistema Nervoso Central/uso terapêutico , Fadiga/tratamento farmacológico , Fadiga/prevenção & controle , Humanos , Modafinila/uso terapêutico , Privação do Sono
5.
BMJ Case Rep ; 14(3)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653852

RESUMO

The COVID-19 pandemic has dealt a devastating blow to healthcare systems globally. Approximately 3.2% of patients infected with COVID-19 require invasive ventilation during the course of the illness. Within this population, 25% of patients are affected with neurological manifestations. Among those who are affected by severe neurological manifestations, some may have acute cerebrovascular complications (5%), impaired consciousness (15%) or exhibit skeletal muscle hypokinesis (20%). The cause of the severe cognitive impairment and hypokinesis is unknown at this time. Potential causes include COVID-19 viral encephalopathy, toxic metabolic encephalopathy, post-intensive care unit syndrome and cerebrovascular pathology. We present a case of a 60 year old patient who sustained a prolonged hospitalization with COVID-19, had a cerebrovascular event and developed a persistent unexplained encephalopathy along with a hypokinetic state. He was treated successfully with modafinil and carbidopa/levodopa showing clinical improvement within 3-7 days and ultimately was able to successfully discharge home.


Assuntos
Encefalopatias , COVID-19 , Carbidopa/administração & dosagem , Hipocinesia , AVC Isquêmico , Levodopa/administração & dosagem , Modafinila/administração & dosagem , Reabilitação/métodos , SARS-CoV-2/isolamento & purificação , Coagulação Sanguínea , Encefalopatias/fisiopatologia , Encefalopatias/virologia , COVID-19/sangue , COVID-19/complicações , COVID-19/fisiopatologia , COVID-19/terapia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Cuidados Críticos/métodos , Combinação de Medicamentos , Humanos , Hipocinesia/diagnóstico , Hipocinesia/etiologia , Hipocinesia/terapia , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/etiologia , AVC Isquêmico/fisiopatologia , AVC Isquêmico/terapia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Respiração Artificial/métodos , Índice de Gravidade de Doença , Resultado do Tratamento , Desmame do Respirador/métodos
6.
Sleep Med ; 80: 315-321, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33631500

RESUMO

BACKGROUND: Few treatments are available for patients with idiopathic hypersomnia (IH). Modafinil, an established treatment for narcolepsy, was tested for efficacy and safety in Japanese patients with IH without long sleep time. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study was conducted at 20 institutions in Japan. Patients who met the diagnostic criteria of IH in the International Classification of Sleep Disorders (second edition) were included. The study comprised a ≥17-day observation period and a 3-week treatment period during which modafinil (200 mg) or placebo was administered orally once daily (in the morning). The primary efficacy endpoint was change in mean sleep latency on the Maintenance of Wakefulness Test (MWT). Adverse events (AEs) were also recorded to evaluate safety. RESULTS: In total, 123 patients were screened and 71 were randomized to receive modafinil (N = 34) or placebo (N = 37). Patients treated with modafinil experienced a significantly prolonged mean sleep latency on the MWT at the end of the study compared with placebo (5.02 min, 95% confidence interval: 3.26-6.77 min; p < 0.001). AEs occurred in 58.8% (20/34) and 27.0% (10/37) of patients in the modafinil and placebo groups, respectively. Frequent AEs in the modafinil group were headache (n = 6), dry mouth (n = 3), and nausea (n = 3); no clinically significant AEs occurred. CONCLUSION: Modafinil was shown to be an effective and safe treatment for excessive daytime sleepiness in patients with IH without long sleep time. CLINICAL TRIAL REGISTRATION: JapicCTI; 142539.


Assuntos
Estimulantes do Sistema Nervoso Central , Distúrbios do Sono por Sonolência Excessiva , Hipersonia Idiopática , Compostos Benzidrílicos/efeitos adversos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Distúrbios do Sono por Sonolência Excessiva/tratamento farmacológico , Método Duplo-Cego , Humanos , Hipersonia Idiopática/tratamento farmacológico , Japão , Modafinila/uso terapêutico , Sono , Resultado do Tratamento , Vigília
7.
Int J Pharm ; 597: 120343, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33545288

RESUMO

Armodafinil is typically used in clinical practice to maintain cognition and wakefulness in patients suffering from sleep deprivation. However, its poor water solubility and large dosage limit its effective application. Herein, we formulated armodafinil in a nanocrystal hydrogel (NCsG) with appropriate fluidity and viscosity, capable of rapidly dissolving after staying in the nasal cavity for > 4 h and then penetrating the mucosa as quickly as possible in vitro. We found that armodafinil NCsG was biologically safe, as it had no visible ciliary toxicity, as well as extremely stable due to the existence of intermolecular hydrogen-bonding forces. Nasal administration of armodafinil NCsG proved to be more efficient and targeted than oral administration due to its preferential absorption in plasma and more-concentrated distribution in the brain. In addition, compared with the model group, sleep-deprived rats treated with NCsG undergoing Morris water maze (MWM) behavioral experiments had shorter escape latency and much more shuttle times across the platform. Meanwhile, in the open-field test (OFT), these same rats had longer periods of movement in the center, longer time spent upright, and lower anxiety, which clearly demonstrated improved cognitive awareness and wakefulness after intranasal administration. Moreover, we speculated that armodafinil NCsG had a protective effect on hippocampal neurons in Cortical Area 1 (CA1), which is closely related to cognitive function, by upregulating brain-derived neurotrophic factor (BDNF) protein expression. Consequently, the intranasal administration of armodafinil NCsG could serve as a promising integrated-control measure for sleep deprivation.


Assuntos
Hidrogéis , Nanopartículas , Animais , Compostos Benzidrílicos , Cognição , Método Duplo-Cego , Humanos , Modafinila , Ratos , Sono
8.
Drug Alcohol Depend ; 221: 108554, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33610094

RESUMO

BACKGROUND: The absence of an FDA-approved medication for the treatment of cocaine use disorder (CUD) may, in part, reflect the varying conditions present when the decision to use cocaine is made, with one medication unlikely to work under all conditions. The objective of this double-blind, placebo-controlled, human laboratory study was to test the effects of modafinil, a medication with mixed efficacy for the treatment of CUD, using a novel self-administration procedure designed to model distinct clinical scenarios. METHODS: During modafinil maintenance (0, 300 mg/day), participants chose to self-administer up to 7 doses of smoked cocaine (25 mg) under 9 conditions: immediately after exposure to: (a) cues associated with cocaine and a non-contingent cocaine administration, i.e. 'prime' (25 mg), (b) only cocaine cues, and (c) neither cues nor cocaine. Each condition was tested when self-administered cocaine cost $5, $10 and $15/dose. RESULTS: Nontreatment-seeking cocaine smokers (3 F,13 M), spending $388 ± 218/week on cocaine and with no history of alcohol use disorder, completed the study. Relative to placebo, modafinil robustly attenuated self-administration when cocaine was expensive ($10,$15/dose) and when there was no 'prime.' Modafinil had no effect on self-administration when cocaine was inexpensive ($5/dose) or when participants received a 'prime.' CONCLUSIONS: Modafinil's effects on cocaine-taking varied substantially as a function of recent cocaine exposure and cost, which may help explain the mixed clinical findings. Modafinil may be most effective for preventing relapse in abstinent patients, particularly under conditions in which cocaine is costly, rather than initiating abstinence for those continuing to use cocaine.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Modafinila/uso terapêutico , Adulto , Alcoolismo/tratamento farmacológico , Compostos Benzidrílicos/farmacologia , Cocaína/administração & dosagem , Transtornos Relacionados ao Uso de Cocaína/terapia , Sinais (Psicologia) , Método Duplo-Cego , Feminino , Humanos , Masculino , Atividade Motora/efeitos dos fármacos , Autoadministração
9.
Transl Psychiatry ; 11(1): 116, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558464

RESUMO

Depression, cognitive deficits, and sleep disturbances are common and often severe in menopausal women. Hormone replacement cannot effectively alleviate these symptoms and sometimes elicits life-threatening adverse reactions. Exploring effective therapies to target psychological problems is urgently needed. In this work, we developed a mouse model of menopause by bilateral ovariectomies (OVXs) and investigated whether menopausal mental symptoms can be ameliorated by psychostimulant modafinil (MOD) as well as explored the underlying mechanisms. At ~3 weeks after OVXs, mice got daily intraperitoneal administrations of MOD at the beginning of the active phase. Several behavioral tests and electroencephalogram (EEG) recordings were conducted. Electrophysiological and immunohistochemical experiments were carried out to evaluate the synaptic plasticity and neurogenesis, respectively. We found that chronic MOD administration in OVX mice significantly decreased immobility time. The spatial memory performance of OVX mice improved significantly in response to MOD administration in the Morris water-maze test. The OVX mice were characterized by an attenuation of hippocampal synaptic transmission and synaptic long-term potentiation and had fewer 5-ethynyl-2'-deoxyuridine-labeled cells in the dentate gyrus, which were restored after MOD administration. Antagonists of dopamine D1 and D2 receptors and GABAA receptor agonists were involved in MOD-exerted anti-depressant actions and augments of hippocampal neurogenesis in OVX mice. Moreover, night-dosed MOD therapy significantly promoted the night-time delta-band EEG power during wakefulness and the day-time rapid eye movement sleep amount, which were significantly reduced by OVXs. Collectively, these findings suggest that MOD is a promising therapeutic candidate for menopausal women.


Assuntos
Hipocampo , Memória Espacial , Animais , Feminino , Menopausa , Camundongos , Modafinila , Plasticidade Neuronal , Sono REM , Comportamento Espacial
10.
Ann Am Thorac Soc ; 18(5): 757-768, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33621163

RESUMO

Many patients with obstructive sleep apnea (OSA) experience excessive daytime sleepiness (EDS), which can negatively affect daily functioning, cognition, mood, and other aspects of well-being. Although EDS can be reduced with primary OSA treatment, such as continuous positive airway pressure (CPAP) therapy, a significant proportion of patients continue to experience EDS despite receiving optimized therapy for OSA. This article reviews the pathophysiology and clinical evaluation and management of EDS in patients with OSA. The mechanisms underlying EDS in CPAP-treated patients remain unclear. Experimental risk factors include chronic intermittent hypoxia and sleep fragmentation, which lead to oxidative injury and changes in neurons and brain circuit connectedness involving noradrenergic and dopaminergic neurotransmission in wake-promoting regions of the brain. In addition, neuroimaging studies have shown alterations in the brain's white matter and gray matter in patients with OSA and EDS. Clinical management of EDS begins with ruling out other potential causes of EDS and evaluating its severity. Tools to evaluate EDS include objective and self-reported assessments of sleepiness, as well as cognitive assessments. Patients who experience residual EDS despite primary OSA therapy may benefit from wake-promoting pharmacotherapy. Agents that inhibit reuptake of dopamine or of dopamine and norepinephrine (modafinil/armodafinil and solriamfetol, respectively) have demonstrated efficacy in reducing EDS and improving quality of life in patients with OSA. Additional research is needed on the effects of wake-promoting treatments on cognition in these patients and to identify individual or disorder-specific responses.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Apneia Obstrutiva do Sono , Pressão Positiva Contínua nas Vias Aéreas , Distúrbios do Sono por Sonolência Excessiva/etiologia , Distúrbios do Sono por Sonolência Excessiva/terapia , Humanos , Modafinila , Qualidade de Vida , Apneia Obstrutiva do Sono/terapia
11.
Sleep ; 44(6)2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-33406259

RESUMO

Methamphetamine is a potent and highly addictive psychostimulant, and one of the most widely used illicit drugs. Over recent years, its global usage and seizure have been on a rapid rise, with growing detrimental effects on mental and physical health, and devastating psychosocial impact pressing for intervention. Among the unwanted effects of methamphetamine, acute and long-term sleep impairments are of major concern, posing a significant therapeutic challenge, and a cause of addiction relapse. Unraveling mechanisms and functional correlates of methamphetamine-related sleep and circadian disruption are, therefore, of key relevance to translational and clinical psychiatry. In this article, we review the mounting evidence for the acute and long-term impairements of sleep-wake behavior and circadian activity caused by single or recurring methamphetamine usage and withdrawal. Factors contributing to the severity of sleep loss and related cognitive deficit, with risks of relapse are discussed. Key molecular players mediating methamphetamine-induced dopamine release and neuromodulation are considered, with wake-promoting effects in mesolimbic circuits. The effects on various sleep phases and related changes in dopamine levels in selected subcortical structures are reviewed and compared to other psychostimulants with similar action mechanisms. A critical appraisal is presented of the therapeutic use of modafinil, countering sleep, and circadian rhythm impairments. Finally, emerging knowledge gaps and methodical limitations are highlighted along with the areas for future research and therapeutic translation.


Assuntos
Estimulantes do Sistema Nervoso Central , Metanfetamina , Estimulantes do Sistema Nervoso Central/efeitos adversos , Dopamina , Metanfetamina/efeitos adversos , Modafinila , Sono
12.
Ann Pharmacother ; 55(10): 1254-1266, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33435717

RESUMO

OBJECTIVE: To describe the efficacy and safety of pharmacologic neurostimulants after neurological injuries such as ischemic or hemorrhagic stroke and traumatic brain injury (TBI), critically evaluate the available literature, and make recommendations regarding which neurostimulants should be considered for use in clinical practice. DATA SOURCES: A literature search of PubMed was performed (1953 to October 2020) to identify relevant articles. Search terms included the following: "neurostimulant, neurorehabilitation" AND "traumatic brain injury, cerebrovascular accident, or stroke." This review is limited to prospective studies and observational trials. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language studies conducted in humans were considered. DATA SYNTHESIS: Cognitive and motor deficits caused by stroke and TBI account for high rates of long-term disability. Although not well-established, pharmacologic agents, broadly characterized as neurostimulants, may be prescribed after brain injury to treat these deficits. When prescribing these medications, it is imperative to be aware of the supporting evidence in order to accurately gauge the risk-benefit profile of each agent. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The following presents a literature review critically evaluating clinical studies that investigate neurostimulant use after brain injury. The intent of this review is to serve as an evidence-based guide for clinicians. CONCLUSIONS: The pharmacologic agent with the most supporting literature is amantadine used for cognitive improvement after TBI. Other neurostimulants with positive, despite more limited, evidence include methylphenidate, modafinil, levodopa, and citalopram. Caution is warranted with other neurostimulants given higher rates of adverse effects or lack of benefit observed in clinical trials.


Assuntos
Lesões Encefálicas , Acidente Vascular Cerebral , Lesões Encefálicas/tratamento farmacológico , Humanos , Modafinila , Estudos Prospectivos , Medição de Risco
13.
Psychopharmacology (Berl) ; 238(2): 441-451, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33201262

RESUMO

RATIONAL: At all times humans have made attempts to improve their cognitive abilities by different means, among others, with the use of stimulants. Widely available stimulants such as caffeine, but also prescription substances such as methylphenidate and modafinil, are being used by healthy individuals to enhance cognitive performance. OBJECTIVES: There is a lack of knowledge on the effects of prescription stimulants when taken by healthy individuals (as compared with patients) and especially on the effects of different substances across different cognitive domains. METHODS: We conducted a pilot study with three arms in which male participants received placebo and one of three stimulants (caffeine, methylphenidate, modafinil) and assessed cognitive performance with a test battery that captures various cognitive domains. RESULTS: Our study showed some moderate effects of the three stimulants tested. Methylphenidate had positive effects on self-reported fatigue as well as on declarative memory 24 hours after learning; caffeine had a positive effect on sustained attention; there was no significant effect of modafinil in any of the instruments of our test battery. All stimulants were well tolerated, and no trade-off negative effects on other cognitive domains were found. CONCLUSIONS: The few observed significant positive effects of the tested stimulants were domain-specific and of rather low magnitude. The results can inform the use of stimulants for cognitive enhancement purposes as well as direct further research to investigate the effects of stimulants on specific cognitive domains that seem most promising, possibly by using tasks that are more demanding.


Assuntos
Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Cognição/efeitos dos fármacos , Metilfenidato/farmacologia , Modafinila/farmacologia , Nootrópicos/farmacologia , Adulto , Atenção/efeitos dos fármacos , Método Duplo-Cego , Fadiga/prevenção & controle , Humanos , Masculino , Projetos Piloto , Resultado do Tratamento , Adulto Jovem
14.
Expert Opin Pharmacother ; 22(2): 155-162, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32941089

RESUMO

INTRODUCTION: Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep. Treatment of narcolepsy remains challenging and current therapy is strictly symptomatically based. AREAS COVERED: The present manuscript is based on an extensive Internet and PubMed search from 1990 to 2020. It is focused on the clinical and pharmacological properties of pitolisant in the treatment of narcolepsy. EXPERT OPINION: Currently there is no cure for narcolepsy. Although efforts have been made, current treatments do not always allow to obtain an optimal control of symptoms. Pitolisant is an antagonist/inverse agonist of the histamine H3 autoreceptor. Its mechanism of action is novel and distinctive compared to the other available therapies for narcolepsy. Clinical trials suggest that pitolisant administered at a dose of ≤36 mg/day is an effective treatment option for narcolepsy, reducing EDS and cataplexy. Pitolisant is available as oral tablets and offers a convenient once-daily regimen. Pitolisant is generally well tolerated and showed minimal abuse potential in animals and humans. Long-term studies comparing the effectiveness and tolerability of pitolisant with active drugs (e.g. modafinil, sodium oxybate) are needed.


Assuntos
Cataplexia/tratamento farmacológico , Narcolepsia/tratamento farmacológico , Piperidinas/administração & dosagem , Animais , Humanos , Modafinila/uso terapêutico , Sono/efeitos dos fármacos , Oxibato de Sódio/uso terapêutico , Resultado do Tratamento
15.
J Plast Reconstr Aesthet Surg ; 74(6): 1346-1354, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33279429

RESUMO

BACKGROUND: The brain-stimulating agent modafinil acts through nitric oxide (NO) and adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, involved in the skin flap survival (SFS). The main aim of this study was to investigate the efficacy of modafinil on SFS in rats through the involvement of NO pathway and KATP channels. METHODS: Using controlled experiment study design, we enrolled a sample of Wistar male rats. Different doses of modafinil (10, 25, 50, and 100 mg/kg) were injected intraperitoneally (i.p.) before the surgery. L-NAME (non-selective nitric oxide synthase [NOS] inhibitor), aminoguanidine (inducible NOS inhibitor), and 7-nitroindazole (neuronal NOS inhibitor) were administered prior to modafinil. The role of KATP channels was determined by coadministering glibenclamide (KATP channel blocker) or cromakalim (KATP channel opener) with modafinil. The predictor variables were administration of different doses of modafinil, and the coadministration of modafinil with L-NAME, aminoguanidine, 7-nitroindazole, glibenclamide, and cromakalim. The main outcome variables included the percentage of necrotic area (PNA) in flap tissues, histopathological results, vascular endothelial growth factor (VEGF) immunohistochemical (IHC) staining, and nitrite concentrations. Appropriate statistics were computed considering p-value ≤ 0.05 significant. RESULTS: Modafinil 25 mg/kg was the most effective dose (PNA: 26 [95% CI: 19-33]) vs. control (PNA: 81 [95% CI: 71-92]) (p< 0.001). All NOS inhibitors significantly reversed the protective effect of modafinil (p< 0.001). Non-effective dose of cromakalim had a synergistic effect with the sub-effective dose of modafinil (10 mg/kg), while glibenclamide reversed the effect of modafinil 25 mg/kg (p< 0.001). CONCLUSIONS: Modafinil increases SFS mediated by NO pathway and KATP channels, which could therefore be a target to improve SFS.


Assuntos
Sobrevivência de Enxerto , Modafinila/farmacologia , Óxido Nítrico/metabolismo , Canais de Potássio/metabolismo , Transplante de Pele/métodos , Retalhos Cirúrgicos/patologia , Animais , Estimulantes do Sistema Nervoso Central/farmacologia , Relação Dose-Resposta a Droga , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/fisiologia , Injeções Intraperitoneais , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Necrose/prevenção & controle , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Resultado do Tratamento
16.
Lancet Neurol ; 20(1): 38-48, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33242419

RESUMO

BACKGROUND: Methylphenidate, modafinil, and amantadine are commonly prescribed medications for alleviating fatigue in multiple sclerosis; however, the evidence supporting their efficacy is sparse and conflicting. Our goal was to compare the efficacy of these three medications with each other and placebo in patients with multiple sclerosis fatigue. METHODS: In this randomised, placebo-controlled, four-sequence, four-period, crossover, double-blind trial, patients with multiple sclerosis who reported fatigue and had a Modified Fatigue Impact Scale (MFIS) score of more than 33 were recruited at two academic multiple sclerosis centres in the USA. Participants received oral amantadine (up to 100 mg twice daily), modafinil (up to 100 mg twice daily), methylphenidate (up to 10 mg twice daily), or placebo, each given for up to 6 weeks. All patients were intended to receive all four study medications, in turn, in one of four different sequences with 2-week washout periods between medications. A biostatistician prepared a concealed allocation schedule, stratified by site, randomly assigning a sequence of medications in approximately a 1:1:1:1 ratio, in blocks of eight, to a consecutive series of numbers. The statistician and pharmacists had no role in assessing the participants or collecting data, and the participants, caregivers, and assessors were masked to allocation. The primary outcome measure was the MFIS measured while taking the highest tolerated dose at week 5 of each medication period, analysed by use of a linear mixed-effect regression model. This trial is registered with ClinicalTrials.gov, NCT03185065 and is closed. FINDINGS: Between Oct 4, 2017, and Feb 27, 2019, of 169 patients screened, 141 patients were enrolled and randomly assigned to one of four medication administration sequences: 35 (25%) patients to the amantadine, placebo, modafinil, and methylphenidate sequence; 34 (24%) patients to the placebo, methylphenidate, amantadine, and modafinil sequence; 35 (25%) patients to the modafinil, amantadine, methylphenidate, and placebo sequence; and 37 (26%) patients to the methylphenidate, modafinil, placebo, and amantadine sequence. Data from 136 participants were available for the intention-to-treat analysis of the primary outcome. The estimated mean values of MFIS total scores at baseline and the maximal tolerated dose were as follows: 51·3 (95% CI 49·0-53·6) at baseline, 40·6 (38·2-43·1) with placebo, 41·3 (38·8-43·7) with amantadine, 39·0 (36·6-41·4) with modafinil, and 38·6 (36·2-41·0) with methylphenidate (p=0·20 for the overall medication effect in the linear mixed-effect regression model). As compared with placebo (38 [31%] of 124 patients), higher proportions of participants reported adverse events while taking amantadine (49 [39%] of 127 patients), modafinil (50 [40%] of 125 patients), and methylphenidate (51 [40%] of 129 patients). Three serious adverse events occurred during the study (pulmonary embolism and myocarditis while taking amantadine, and a multiple sclerosis exacerbation requiring hospital admission while taking modafinil). INTERPRETATION: Amantadine, modafinil, and methylphenidate were not superior to placebo in improving multiple sclerosis fatigue and caused more frequent adverse events. The results of this study do not support an indiscriminate use of amantadine, modafinil, or methylphenidate for the treatment of fatigue in multiple sclerosis. FUNDING: Patient-Centered Outcomes Research Institute.


Assuntos
Amantadina/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Fadiga/tratamento farmacológico , Fadiga/etiologia , Metilfenidato/farmacologia , Modafinila/farmacologia , Esclerose Múltipla/complicações , Avaliação de Resultados em Cuidados de Saúde , Adulto , Amantadina/administração & dosagem , Amantadina/efeitos adversos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Metilfenidato/administração & dosagem , Metilfenidato/efeitos adversos , Pessoa de Meia-Idade , Modafinila/administração & dosagem , Modafinila/efeitos adversos , Índice de Gravidade de Doença
18.
PLoS One ; 15(11): e0241968, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33216781

RESUMO

INTRODUCTION AND AIMS: The non-medical use of prescription stimulants such as methylphenidate, dexamphetamine and modafinil is increasing in popularity within tertiary academic settings. There is a paucity of information on awareness, attitudes, and acceptability by professionals of use in this context. This study aimed to investigate professionals' knowledge of and attitudes towards the use of cognitive enhancers (CEs) in academic settings, and their willingness to use a hypothetical CE. DESIGN AND METHODS: A mail survey was sent to doctors, pharmacists, nurses, accountants and lawyers in New Zealand. These disciplines were chosen as they require professional registration to practice. The questionnaire comprised four sections: (1) demographics, (2) knowledge of CEs, (3) attitudes towards the use of CEs, and (4) willingness to use hypothetical CEs. RESULTS: The response rate was 34.5% (414/1200). Overall, participants strongly disagreed that it was fair to allow university students to use CEs for cognitive enhancement (Mdn = 1, IQR: 1,3), or that it is ethical for students without a prescription to use cognitive enhancers for any reason (Mdn = 1, IQR: 1,2). Professions differed in their attitudes towards whether it is ethical for students without a prescription to use CEs for any reason (p = 0.001, H 31.527). DISCUSSION AND CONCLUSION: Divergent views and lack of clear consensus within professions and between professionals on the use of CEs have the potential to influence both professionals and students as future professionals. These divergent views may stem from differences in the core values of self-identity as well as extrinsic factors of acceptability within the profession in balancing the elements of opportunity, fairness and authenticity in cognitive enhancement. Further research is required to inform the development of policy and guidelines that are congruent with all professions.


Assuntos
Cognição/efeitos dos fármacos , Pessoal de Saúde/psicologia , Medicamentos sob Prescrição/uso terapêutico , Adulto , Idoso , Atitude do Pessoal de Saúde , Estimulantes do Sistema Nervoso Central/uso terapêutico , Dextroanfetamina/uso terapêutico , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Metilfenidato/uso terapêutico , Pessoa de Meia-Idade , Modafinila/uso terapêutico , Nova Zelândia , Estudantes/psicologia , Inquéritos e Questionários , Universidades , Adulto Jovem
19.
Int Immunopharmacol ; 88: 106983, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33182022

RESUMO

OBJECTIVE: Intestinal ischemia reperfusion (IR) is a pathophysiologic process that leads to oxidative stress and acute inflammatory responses. Understanding the mechanisms explaining this inflammation is essential to developing therapeutic strategies. Therefore, the purpose of this study was to evaluate the protective outcome of modafinil (Mod) against intestinal damages caused by intestinal IR injury. METHODS/MATERIALS: Fourty adult Male Wistar rats were randomly divided into four groups: sham control group; intestinal IR group; Mod pre-treated IR group and Mod post-treated IR group. Mod in a dose of 10 mg/kg was injected intraperitoneally once daily for 7 days pre or post IR treatment. RESULTS: Mod significantly attenuated the IR induced elevations in intestinal malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin 1-ß (IL-1ß) and P-glycoprotein (P-gp) levels, caspase-3 activity. However, a significant increase in TAC was reported as compared with the IR group but its post-treated IR group was highly protective. Mod post-treatment down-regulated the IR induced cyclo-oxygenase-2 (COX-2) over-expression. Distorted mucosa with loss of surface epithelial cells, epithelial separation oedematous lamina propria and inflammatory cellular infiltration detected by histopathological examination of intestinal tissue, were markedly ameliorated by Mod post-treatment. On the other hand, Mod pre-treatment showed less protection against intestinal IR in rats. CONCLUSION: Current study suggests that Mod post-treatment ameliorated intestinal damages, so it can be considered a potential therapeutic agent to protect against the major clinical challenge of intestinal injury resulting from IR.


Assuntos
Indutores do Citocromo P-450 CYP3A/uso terapêutico , Enteropatias/tratamento farmacológico , Modafinila/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Caspase 3/genética , Caspase 3/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Enteropatias/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
20.
J Stroke Cerebrovasc Dis ; 29(11): 105213, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066879

RESUMO

BACKGROUND: In stroke survivors, post-stroke fatigue predicts dependency in daily living and failure to return to work. Modafinil shows promise as a pharmacotherapy to reduce post-stroke fatigue and related sequelae, e.g., poorer functional and clinical outcomes. AIMS: This study explored the cost-effectiveness of modafinil in treating post-stroke fatigue in the Australian context, by determining its incremental cost-effectiveness ratio (ICER) and by simulating the potential cost-savings on a national scale, through a re-analysis of MIDAS trial data. METHODS: A post hoc cost-effectiveness analysis was undertaken. Part A: patient-level cost and health effect data (Multidimensional Fatigue Inventory (MFI) scores) were derived from the MIDAS trial and analysis undertaken from a health-system perspective. Part B: a secondary analysis simulated the societal impact of modafinil therapy in terms of national productivity costs. RESULTS: Part A: Mean cost of modafinil treatment was AUD$3.60/day/patient for a minimally clinically important change (10 points) in total MFI fatigue score, i.e., AUD$0.36/day/unit change in fatigue score per patient. For the base case scenario, the ICER of using modafinil (versus placebo) was AUD$131.73 ($90.17 - 248.15, for minimum and maximum costs, respectively). Part B: The potential productivity cost-savings to society were calculated as nearly AUD$467 million over 1 year, and up to $383,471,991,248 over 10 years, from the widespread use of modafinil treatment in the Australian population of working-age stroke-survivors, representing a significant societal benefit. CONCLUSIONS: Modafinil is a highly cost-effective treatment for post-stroke fatigue, offering significant productivity gains and potential cost-savings to society from the widespread use of modafinil treatment in the Australian population of working-age stroke-survivors.


Assuntos
Estimulantes do Sistema Nervoso Central/economia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Custos de Medicamentos , Fadiga/tratamento farmacológico , Fadiga/economia , Modafinila/economia , Modafinila/uso terapêutico , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/terapia , Idoso , Austrália , Estimulantes do Sistema Nervoso Central/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Redução de Custos , Análise Custo-Benefício , Fadiga/diagnóstico , Fadiga/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila/efeitos adversos , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...