Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Modafinil, (RS)-2-(diphenylmethylsulfinyl)acetamide derivative (Modiodal, Provigil), is a vigilance-promoting agent which reduces sleep episodes by improving wakefulness. It is approved by the USA FDA for narcolepsy, shiftwork sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure. Unlike classical psychostimulants such as amphetamine and amphetamine-like compounds, the awaking effect of modafinil is not associated with a disturbance of nighttime sleep, tolerance, and sensitization. Its precise mechanism of action is still unclear. In animal studies, modafinil and its analogues have been shown to modify dopaminergic, noradrenergic, glutamatergic, GABAergic, serotoninergic, orexinergic, and histaminergic pathways. Besides the approved use in sleep disorders, modafinil has been investigated for the treatment of fatigue, impaired cognition and some symptoms in a number of other disorders. In particular, clinical studies seem to indicate that the drug could be particularly successful in the treatment of depression and its use in major depressive and bipolar disorders, has been suggested. However, the molecular mechanisms underlying this possible effect are still unknown. The present review firstly summarizes the structure-activity relationship studies and the mechanism of action of modafinil and its related compounds. Then, it focuses on data demonstrating that modafinil interacts with serotonin neuronal activity in rat frontal cortex and dorsal raphe nucleus, two brain areas linked together and involved in depression. Preclinical and clinical evidence of a positive interaction between modafinil and classical antidepressant drugs, is also summarized.
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PMID:The vigilance promoting drug modafinil modulates serotonin transmission in the rat prefrontal cortex and dorsal raphe nucleus. Possible relevance for its postulated antidepressant activity. 2251 71

Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system, leading to chronic disability. Fatigue is a common and distressing symptom of MS which is unrelated to its clinical form, stage of development, the degree of disability, or the lesion load on magnetic resonance imaging. Fatigue in MS is associated with excessive daytime sleepiness and autonomic dysfunction. Recently it has been reported that the wakefulness-promoting drug modafinil may relieve fatigue in MS patients and ameliorate the associated cognitive difficulties. However, it is not clear to what extent the anti-fatigue effect of modafinil may be related to its alerting and sympathetic activating effects. We addressed this question by comparing three groups of subjects, MS patients with fatigue, MS patients without fatigue and healthy controls, matched for age and sex, on measures of alertness (self-ratings on the Epworth and Stanford Sleepiness Scales and on a battery of visual analogue scales; critical flicker fusion frequency; Pupillographic Sleepiness Test; choice reaction time) and autonomic function (systolic and diastolic blood pressure, heart rate, pupil diameter), and by examining the effect of a single dose (200 mg) of modafinil on these measures. MS patients with fatigue, compared with healthy controls, had reduced level of alertness on all the tests used; MS patients without fatigue did not differ from healthy controls. MS patients with fatigue had a reduced level of cardiovascular sympathetic activation compared to the other two groups. Modafinil displayed alerting and sympathomimetic effects in all three groups of subjects. As fatigue in MS is associated with reduced levels of alertness and sympathetic activity, modafinil may exert its anti-fatigue effect in MS by correcting these deficiencies. The anti-fatigue effect of modafinil may reflect the activation of the noradrenergic locus coeruleus (LC), since there is evidence that this wakefulness-promoting nucleus is damaged in MS, and that modafinil, probably via the dopaminergic system, can stimulate the LC. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
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PMID:Association of a deficit of arousal with fatigue in multiple sclerosis: effect of modafinil. 2276 94

HIV-related fatigue continues to be the most common complaint of infected people. No physiological factors have been consistent predictors for fatigue; psychosocial factors, particularly depression, have emerged more consistently in studies. While clinicians would want to rule out common causes of fatigue such as hypothyroidism, hypogonadism, or anemia, there is scant research for most interventions, which makes it difficult to make definitive recommendations for their use. Modafinil has the strongest research evidence to date, with multiple studies finding it effective in relieving fatigue. However, researchers must continue to pursue ways to ameliorate fatigue in HIV infection, given the high financial, personal, and social costs suffered by people experiencing it.
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PMID:Fatigue in HIV and AIDS: an analysis of evidence. 2329 Mar 77

Fatigue is a debilitating and pervasive complication of cancer and cancer care. Clinical research investigating potential therapies is hindered by variability in patient histories, different metrics for measuring fatigue, and environmental factors that may affect fatigue. The purpose of this study was to establish an animal model of chemotherapy-related fatigue. Female HSD:ICR mice were treated with doxorubicin (2.5 mg/kg) or saline in 2 cycles (days 1 through 3 and 10 through 12). After treatment, mice were individually housed in cages equipped with running wheels. Open-field activity and motor coordination were examined after each cycle of treatment and after each week of wheel running. In a separate cohort, modafinil (50 mg/kg) was assessed as a potential treatment for fatigue. Doxorubicin administration resulted in greater than 30% less wheel running compared with that of saline controls. Activity differences were specific to wheel running: neither distance traveled in the open field nor motor coordination according to the rotarod test differed between groups. Compared with control values, RBC counts in the doxorubicin group were decreased on days 15 and 22 but recovered to control levels by study completion. Modafinil was efficacious in increasing wheel running in the doxorubicin group. The current results establish an animal model of chemotherapy-related fatigue that recapitulates the physical symptoms of cancer-related fatigue as manifested as decreased voluntary activity. This model is sensitive to pharmaceutical intervention and can be used to screen potential treatments for fatigue.
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PMID:A clinically translatable mouse model for chemotherapy-related fatigue. 2432 24

Fatigue is a common symptom of multiple sclerosis (MS) with negative impacts extending from general functioning to quality of life. Both the cause and consequences of MS fatigue are considered multidimensional and necessitate multidisciplinary treatment for successful symptom management. Clinical practice guidelines suggest medication and rehabilitation for managing fatigue. This review summarized available research literature about three types of fatigue management interventions (exercise, education, and medication) to provide comprehensive perspective on treatment options and facilitate a comparison of their effectiveness. We researched PubMed, Embase, and CINAHL (August 2013). Search terms included multiple sclerosis, fatigue, energy conservation, Amantadine, Modafinil, and randomized controlled trial. The search identified 230 citations. After the full-text review, 18 rehabilitation and 7 pharmacological trials targeting fatigue were selected. Rehabilitation interventions appeared to have stronger and more significant effects on reducing the impact or severity of patient-reported fatigue compared to medication. Pharmacological agents, including fatigue medication, are important but often do not enable people with MS to cope with their existing disabilities. MS fatigue affects various components of one's health and wellbeing. People with MS experiencing fatigue and their healthcare providers should consider a full spectrum of effective fatigue management interventions, from exercise to educational strategies in conjunction with medication.
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PMID:Meta-analysis of three different types of fatigue management interventions for people with multiple sclerosis: exercise, education, and medication. 2496 7

As patients recover from their critical illness, the focus of intensive care unit (ICU) care becomes rehabilitation. Fatigue, excessive daytime somnolence (EDS), and depression can delay their recovery and potentially worsen outcomes. Psychostimulants, particularly modafinil (Provigil), have been shown to alleviate some of these symptoms in various patient populations, and as clinical trials are underway exploring this novel use of the drug, we present a case series of 3 patients in our institution's Thoracic Surgery Intensive Care Unit. Our 3 patients were chosen as a result of their fatigue, EDS, and/or depression, which prolonged their ICU stay and precluded them from participating in physical therapy, an integral component of the rehabilitative process. The patients were given 200 mg of modafinil each morning to increase patient wakefulness, encourage their participation, and enable a more restful sleep during the night. Although the drug was undoubtedly not the sole reason why our patients became more active, the temporal relationship between starting the drug and our patients' clinical improvement makes it likely that it contributed. Based on our observations with these patients, the known effects of modafinil, its safety profile, and the published experiences of others, we believe that modafinil has potential benefits when utilized in some critically ill patients and that the consequences of delayed patient recovery and a prolonged ICU stay may outweigh the risks of potential modafinil side effects.
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PMID:The Use of Modafinil in the Intensive Care Unit. 2571 22

Motor neuron disease is a neurodegenerative disease characterized by loss of upper motor neuron in the motor cortex and lower motor neurons in the brain stem and spinal cord. Death occurs 2-4 years after the onset of the disease. A complex interplay of cellular processes such as mitochondrial dysfunction, oxidative stress, excitotoxicity, and impaired axonal transport are proposed pathogenetic processes underlying neuronal cell loss. Currently evidence exists for the use of riluzole as a disease modifying drug; multidisciplinary team care approach to patient management; noninvasive ventilation for respiratory management; botulinum toxin B for sialorrhoea treatment; palliative care throughout the course of the disease; and Modafinil use for fatigue treatment. Further research is needed in management of dysphagia, bronchial secretion, pseudobulbar affect, spasticity, cramps, insomnia, cognitive impairment, and communication in motor neuron disease.
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PMID:Multidisciplinary Interventions in Motor Neuron Disease. 2631 9

Modafinil or armodafinil (ar/mod) may be considered for patients with approved or unapproved indications, including excessive daytime drowsiness, fatigue, attention-deficit/hyperactivity disorder (ADHD), or addictions. Ar/mod is classified as a psychostimulant, and psychostimulants have been associated with a small risk of seizures. There is no guidance about the use of ar/mod in patients who are at risk of seizures. This article suggests how a physician may explore the safety of ar/mod if indicated in a patient at such risk. In summary, reading the prescribing information, writing to the drug manufacturer, and searching research databases suggest the following: Ar/mod and its metabolites and derivatives have dose-dependent anticonvulsant action in animal models; ar/mod is not associated with seizures as an adverse event in populations at risk, such as those with ADHD, head injury, and brain tumors; it is not associated with worsening of seizure disorder in patients with current seizure disorder; and it is not associated with seizures in overdose. These findings are reassuring. However, not all the data are of high quality, and potential ar/mod interactions with antiepileptic drugs (and other concurrent medications that affect the seizure threshold) need to be considered because ar/mod can induce the metabolism of some drugs and inhibit the metabolism of others. Decisions should be individualized, and decision-making should be a shared effort between patient and physician.
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PMID:A method for deciding about the possible safety of modafinil and armodafinil in patients with seizure disorder. 2684 75

Modafinil (MOD) is a wakefulness-inducing compound prescribed for treatment of excessive daytime sleepiness as a consequence of sleep disturbances such as shift work sleep disorder, obstructive sleep apnea, restless leg syndrome, or narcolepsy. While providing effective results in patients with sleepiness, MOD also produces positive outcomes in the management of fatigue associated with different conditions including depression, cancer, or tiredness in military personnel. Although there is clear evidence of the stimulant effects of MOD, current data also show that administration of this drug apparently induces positive neurobiological effects, such as improvement in memory. However, serious concerns have been raised since some reports have suggested MOD dependence. Taken together, these findings highlight the need to characterize the changes induced by MOD which have been observed in several neurobiological functions. Moreover, further work should follow up on the likely long-term effects of this drug if used for treatment of drowsiness and tiredness. Here, we review and summarize recent findings of the medical uses of MOD in the management of sleepiness and fatigue associated with depression or cancer as well as exhaustion in military personnel. We also discuss the available literature related with the cognitive enhancing properties of this stimulant, as well as what is known and unknown about MOD addiction.
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PMID:An Overview of the Clinical Uses, Pharmacology, and Safety of Modafinil. 2911 23

Modafinil is generally known as a drug with low addiction potential. There are few case reports in the literature demonstrating that Modafinil, stated being capable of diminishing symptoms of attention deficit/hyperactivity disorder (ADHD), causes addiction. In the present article a Modafinil addicted ADHD case, consuming usurious doses (5,000 mg/per day) of Modafinil is presented. The case presented to our psychiatry outpatient clinic due to: requirement of in taking high dose Modafinil in order to achieve the initial effects, difficulty in obtaining the drug, irritability, anxiousness, sleep irregularities, fatigue and unpleasant vivid dreams when he did not use the drug. It was realized that the patient, himself increased doses of Modafinil incrementally, in order to keep its effects on attention symptoms at the same level. It has to be kept in mind that ADHD patients can develop Modafinil addiction. It is necessary to carry out systemic studies on this subject.
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PMID:Modafinil Dependence: A Case with Attention-Deficit/Hyperactivity Disorder. 2959 4


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