Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Modafinil”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources
PubMedDate not supplied

Etiologies and sequelae of excessive daytime sleepiness.

Excessive daytime sleepiness (EDS), the primary complaint of patients seen in sleep clinics, affects up to 12% of the general population. The effects of EDS can be debilitating and even life threatening. Patients with EDS may exhibit psychosocial distress, decreased work or school performance, and increased risk for accidents. The differential diagnosis of EDS requires objective assessments, such as polysomnography and the Multiple Sleep Latency Test. There are four major causes of EDS: (1) central nervous system (CNS) pathologic abnormalities, such as narcolepsy and idiopathic CNS hypersomnia; (2) qualitative or quantitative sleep deficiencies, such as sleep apnea and insufficient nocturnal sleep; (3) misalignments of the body's circadian pacemaker with the environment (eg. jet lag or shift work); and (4) drugs, which can increase sleepiness either therapeutically or as a side effect. Depending on etiology, management strategies for EDS include extension of time in bed, naps, surgery, various medical devices (eg, oral appliances, continuous positive airway pressure), and pharmacotherapy. Pharmacotherapy is generally achieved with stimulants, such as amphetamine sulfate, methylphenidate, and pemoline or newer, safer compounds like modafinil.

Disorders of Excessive Somnolence↗
PubMed1997

[Excessive daytime sleepiness].

When it is not due to an extrinsic origin, somnolence may be the main symptom of various diseases. Among these causes of excessive daytime sleepiness, obstructive sleep apnea syndrome is noteworthy for its very important prevalence, estimated at 4% in adult males. Due to repeated upper airway obstructions during sleep, this disease is efficiently treated by continuous positive airway pressure applied through a nasal masks during sleep. Another syndrome, periodic limb movements during sleep may also lead to a sleep fragmentation at the origin of daytime sleepiness. Its treatment is principally based on dopaminergic agonists. Narcolepsy-cataplexy and idiopathic hypersomnia are two causes of excessive daytime sleepiness in young people. The first is as frequent as multiple sclerosis and the second is ten times less frequent. The treatment of these two diseases is now based on a new French drug: modafinil(Modiodal). Sleep pathology still has only a small place in medical training. Excessive daytime sleepiness is therefore often misdiagnosed. In addition to their major risk of work or road accidents, numerous untreated patients continue to suffer from this very unpleasant symptom, at the origin of a major social handicap.

Adult↗
PubMed1997

Pharmacological aspects of human and canine narcolepsy.

Narcolepsy-cataplexy is a disabling neurological disorder that affects 1/2000 individuals. The main clinical features of narcolepsy, excessive daytime sleepiness and symptoms of abnormal REM sleep (cataplexy, sleep paralysis, hypnagogic hallucinations) are currently treated using amphetamine-like compounds or modafinil and antidepressants. Pharmacological research in the area is facilitated greatly by the existence of a canine model of the disorder. The mode of action of these compounds involves presynaptic activation of adrenergic transmission for the anticataplectic effects of antidepressant compounds and presynaptic activation of dopaminergic transmission for the EEG arousal effects of amphetamine-like stimulants. The mode of action of modafmil is still uncertain, and other neurochemical systems may offer interesting avenues for therapeutic development. Pharmacological and physiological studies using the canine model have identified primary neurochemical and neuroanatomical systems that underlie the expression of abnormal REM sleep and excessive sleepiness in narcolepsy. These involve mostly the pontine and basal forebrain cholinergic, the pontine adrenergic and the mesolimbic and mesocortical dopaminergic systems. These studies confirm a continuing need for basic research in both human and canine narcolepsy, and new treatments that act directly at the level of the primary defect in narcolepsy might be forthcoming.

Animals↗
PubMed2001

Sleep disorders.

Many pharmacologic and nonpharmacologic strategies are available to treat sleep disorders successfully. Conventional stimulants and the new stimulant modafinil have roles to play in the management of narcolepsy and idiopathic hypersomnia. Knowledge of the properties and clinical effects of these drugs allows adequate doses of medications to be used with the goal of attaining as maximal alertness as possible. A range of dopaminergic agents is available to treat restless legs syndrome; other medications such as opiates, benzodiazepines, and anticonvulsants can also be used. Successful use of the dopaminergic agents depends on an understanding of the phenomena of augmentation, rebound, and tolerance. Arousal parasomnias can be treated with behavioral methods such as hypnosis and drug therapy. Clonazepam provides relief of the symptoms in most patients with REM sleep behavior disorder.

Disorders of Excessive Somnolence↗
PubMed2004

[Narcolepsy, from Westphal to hypocretin].

CLINICAL DATA: Narcolepsy is a poorly known disease, though not exceptional, with a prevalence of 25 to 35 per 100,000 according to various surveys. Its onset can be anytime from childhood to the fifties with a peak in the second decade. It is characterized by two cardinal symptoms, irresistible sleep episodes and cataplexy or sudden loss of muscle tone triggered by emotional situations. The other symptoms, referred to as accessory due to their inconstancy, are hypnagogic hallucinations, sleep paralysis and disturbed nocturnal sleep. Its diagnosis relies on the identification of the cardinal symptoms. Laboratory tests are required to confirm the diagnosis before initiation of a life-long treatment. Theses test include: all-night and daytime polysomnography documenting sleep-onset REM periods, HLA typing, showing the association with HLA DQB1*0602, and, in unclear cases only, measurement of cerebro-spinal fluid (CSF) hypocretine-1 showing values below 110pg/ml, highly specific of narcolepsy with cataplexy. Pathophysiology owes a lot to the existence of a natural canine model, the narcoleptic dog. Irresistible sleep episodes and cataplexy exhibit different pharmacological control, the former depending on dopaminergic systems and the latter on noradrenergic systems. The most remarkable findings of the last twenty years are the close association with HLA DQB1*0602, the identification of a mutation of hypocretin receptor 2 in the narcoleptic dog and the absence of CSF hypocretin-1 in 90% of patients. An autoimmune mechanism is suggested but not evidenced. THREE-FOLD TREATMENT: First line treatment of irresistible sleep episodes in modafinil, Cataplexy or tricyclic antidepressants or sodium oxybate, and disturbed nocturnal sleep by hypnotics or sodium oxybate. Current therapeutic research is oriented towards hypocretin agonists and immunosuppressors.

Animals↗
PubMed2001

Current concepts in the etiology, diagnosis and treatment of narcolepsy.

Background and purpose: Narcolepsy is the most common neurologic cause of excessive daytime sleepiness. Rapid eye movement (REM) sleep phenomena such as cataplexy, sleep paralysis and hypnagogic hallucinations can also occur. Cataplexy, a sudden bilateral loss of muscle tone usually brought on by emotional reactions such as excitement, is essentially unique to narcolepsy. Narcolepsy, which has a prevalence of 0.02-0.05% in the US, has a profound influence on the quality of life and safety of affected individuals.Patients and methods: The most characteristic and striking physiological abnormality observed in narcolepsy is the sleep-onset REM, or the occurrence of REM sleep at, or within 20 min of, the onset of sleep. The diagnosis is established by nocturnal polysomnography, and the Multiple Sleep Latency Test (MSLT).Results: Familial cases of narcolepsy have been reported, with the risk to first-degree relatives estimated at 1-2%; however, most cases are sporadic and the syndrome is generally believed to involve environmental factors acting on a specific genetic background. The observation of an HLA association in narcolepsy suggests that autoimmunity may play a role in the disorder. However, extensive studies have failed to find convincing evidence of an autoimmune process. Patients with narcolepsy have recently been shown to be deficient in hypocretin, also called orexin, in the cerebrospinal fluid and have a reduction in hypocretin cells in the lateral hypothalamus. This suggests that hypocretins could potentially provide a novel therapeutic approach to the treatment of narcolepsy.Conclusions: Although non-pharmacologic measures can be helpful in treating narcolepsy, most patients require pharmacotherapy that includes psychostimulants or modafinil. Cataplexy is controlled by tricyclic antidepressants or selective serotonin reuptake inhibitors.

Journal Article↗
PubMed2002

Narcolepsy and psychopathology: is there an association?

BACKGROUND: It is widely believed that patients with narcolepsy show high rates of associated psychiatric disturbance, especially schizophrenia and depression. However, surveys have produced conflicting findings and have not addressed the potential confounding effects of stimulant drug treatment. METHOD: Forty-five patients with narcolepsy attending a sleep disorder clinic and 50 matched normal controls underwent structured psychiatric interview. Using a 'lifetime' approach, psychiatric symptoms and diagnoses were established for both groups. RESULTS: Four of the narcolepsy patients but none of the controls had experienced psychotic symptoms. All four patients were taking amphetamines, and the symptoms resolved when the dose was lowered or treatment was changed to modafinil. The lifetime frequency of various depressive syndromes did not differ significantly between the groups. CONCLUSIONS: Contrary to previous claims this study found little to suggest that narcolepsy is associated with schizophrenia. Nor, despite its serious social and occupational consequences, does narcolepsy appear to be associated with an increased frequency of diagnosable depressive disorders.

Journal Article↗
PubMed2005

Review of awakening agents.

Brain injuries are a serious burden of illness to Canada and the US. Advances in managing head trauma have allowed more patients to emerge from decreased levels of consciousness and helped them cope with neurocognitive, neurobehavioural, and neuropsychiatric deficits. In this article, we review the current (1986-2002) evidence surrounding the pharmacological management of arousal states and the aforementioned neurological sequelae of head injury in either acute or chronic conditions. This article will review the evidence for the use of psychostimulants (methylphenidate), antidepressants (amitriptyline, selective serotonin reuptake inhibitors, and buproprion), Parkinson's medications (amantadine, bromocriptine, carbidopa/levodopa), anticonvulsants (valproic acid), modafinil (Provigil), lactate, hyperbaric oxygen chamber, electroconvulsive therapy, and transmagnetic stimulation, in patients following a head injury. The review did not include all anticonvulsants, neuroleptics, beta-blockers, benzodiazepines, azospirones or cognitive enhancers. Unfortunately, the quality of the evidence is generally poor, and sometimes conflicting, which in turn results in indecisive guidelines for treating patients. Accepting the inherent flaws in the evidence we feel that this paper may serve as a stepping-stone for future researchers to improve data gathering that targets neurocognitive, neurobehavioural and neuropsychiatric symptoms following a head injury.

Brain Injuries↗
PubMed2004

Therapeutic alternatives for difficult-to-treat depression: a narrative review of the state of the evidence.

Despite the large number of depressed patients who do not respond to first-line antidepressants, the evidence base of alternate strategies is quite thin. In this article, a simple 5-stage system for categorizing treatment-resistant depression (TRD) is described and the evidence pertaining to the major strategies currently utilized is summarized using four grades, ranging from D (case reports only) to A (multiple positive placebo-controlled trials). It is concluded that the level of evidence supporting many of the contemporary strategies used for TRD (eg, combinations of antidepressants and augmentation with medications such as pindolol, buspirone, or modafinil) is scanty at best. Even the fundamental question concerning "to augment or to switch" is not answerable with available data. It is noted that the best-documented treatments (ie, lithium augmentation, switching to a monoamine oxidase inhibitor, and electroconvulsive therapy) are among the least utilized. This state of affairs will improve with completion of the studies of Systematic Treatment Alternatives to Relieve Depression, a large multicenter study of difficult-to-treat depression funded by the National Institute of Mental Health. There is a need for greater collaboration among academicians and organizations, such as the American Psychiatric Association, the National Institute of Mental Health, and the pharmaceutical industry, to ensure that sufficient research is conducted so that clinician's choices for patients with TRD can be guided by empirical evidence.

Antidepressive Agents↗
PubMed2004

The many faces of fatigue in major depressive disorder.

Fatigue is a common complaint in the community and medical care settings. Different studies show a high comorbidity between fatigue and depressive disorder. Furthermore, fatigue is an important somatic symptom of depressive disorder and one of the main depressive presentations in primary-care medicine. Fatigue shows a slow response to antidepressant treatment and psychotherapy. Improved work performance is strongly correlated to improvement in energy. However, the assessment and treatment of fatigue in depressive disorder remains understudied. Different definitions of fatigue in depressive disorder are applied in DSM-IV and ICD-10, and depression rating scales all show a different coverage of this core depressive symptom, thereby hampering scientific research. Serotonin, norepinephrine, dopamine and histamine mediate symptoms of fatigue in depressive disorder. Although few data address the effect of antidepressants or augmentation strategies on fatigue-related symptoms, there is a pharmacological rationale for using antidepressant monotherapies, such as venlafaxine, bupropion, sertraline, fluoxetine, or augmentation of first-line treatment with stimulants or modafinil.

Antidepressive Agents↗
PubMed2005

Further structure-activity relationship studies of piperidine-based monoamine transporter inhibitors: effects of piperidine ring stereochemistry on potency. Identification of norepinephrine transporter selective ligands and broad-spectrum transporter inhibitors.

4-(4-Chlorophenyl)piperidine analogues each bearing a thioacetamide side chain appendage similar to that found in the wake-promoting drug modafinil have been synthesized. The transporter inhibitory activity of both the cis and trans isomers of these 3,4-disubstituted piperidines in both their (+)- and (-)-enantiomeric forms was determined. These studies reveal that the (-)-cis analogues exhibit dopamine transporter/norepinephrine transporter (DAT/NET) selectivity as was previously reported for the (+)-trans analogues. On the other hand, the (-)-trans and the (+)-cis isomers show serotonin transporter (SERT) or SERT/NET selectivity. Among them, (+)-cis-5b shows a low nanomolar Ki for the NET with 39-fold and 321-fold lower potency at the DAT and SERT, respectively, thus making it a useful pharmacological research tool for exploring NET-associated behavioral signatures. On the other hand, several of the compounds described herein, such as (+)-trans-5c, show comparable activity at all three transporters. Because broad-spectrum transporter inhibitors have been hypothesized to exhibit a more rapid onset of action and/or a greater efficacy as antidepressant agents than those selective for SERT or SERT + NET, some of the present compounds will be valuable to study in animal models of depression.

Animals↗
PubMed2002

Attention deficit disorder in adults.

ADHD/ADD, once thought to occur only in children, is now recognized as continuing into adulthood in many people. In order to be labeled as such, signs and symptoms must start before age 7 and are primarily characterized by inattention, distractibility, and impulsiveness. Although the exact mechanism is unknown, a number of associated neurochemical and structural abnormalities have been observed. This disorder can negatively affect the educational, social, and occupational lives of those who suffer from its symptoms. It interferes with the ability to establish and maintain close relationships. Pharmacotherapy remains the primary mode of treatment. Stimulants such as dextroamphetamine and methylphenidate are the main drugs utilized; they are available in immediate and longer duration versions. Bupropion is another important medicinal option, and there are a variety of other miscellaneous medications to consider, including modafinil, venlafaxine, tricyclic antidepressants, and guanfacine. Psychotherapy is shown to help control impulsiveness, form more satisfactory relationships, rear children more effectively, and improve organizational and problem-solving skills.

Adult↗
PubMed2001

Comparison in symptoms between aged and younger patients with narcolepsy.

We investigated the age-related changes in symptoms in narcolepsy. Fifty patients, 65-year-old and over (aged group), were recruited from the National Narcolepsy Registry. Thirty-four patients, younger than 65 (younger group), were selected by random sampling. Although there was no difference in the age of disease onset between the two groups, the age of diagnosis was significantly earlier for the younger group. Methylphenidate was used significantly more in the aged group, and modafinil in the younger group. The aged group had lower total scores on the Ullanlinna Narcolepsy Scale, because the scores for cataplexy were significantly less for the aged group. There was no significant difference in excessive daytime sleepiness between the two groups.

Adolescent↗
PubMed2003

[Therapy of day time fatigue in patients with multiple sclerosis].

Fatigue is the most common symptom of multiple sclerosis. 75%-90% of patients with multiple sclerosis report having fatigue, and 50%-60% describe it as the worst symptom of their disease. Fatigue is significantly associated with reduced quality of life and is also a major reason for unemployment, especially for patients with otherwise minor disability. The mechanisms underlying abnormal levels of fatigue in multiple sclerosis are poorly understood. To date, drug treatment has been only partially successful in alleviating fatigue, and effects vary widely from patient to patient. Amantadine and modafinil showed to be effective in the treatment of fatigue in some studies. Non-pharmacological management of fatigue in multiple sclerosis includes inpatient rehabilitation and endurance training. There is also evidence, that pulsing electromagnetic fields may improve fatigue associated with multiple sclerosis. This paper summarizes the recent literature on pathophysiology, diagnosis and therapy of the most common symptom of multiple sclerosis.

Central Nervous System Stimulants↗
PubMed2001

Idiopathic Hypersomnia.

In contrast to narcolepsy and the Kleine-Levin syndrome, idiopathic hypersomnia is a recently described sleep disorder. Absence of associated clinical features such as cataplexy or megaphagia and characteristic polysomnographic features such as sleep-onset REM episodes render positive diagnosis more uncertain in idiopathic hypersomnia than in the fwo former conditions. Consequently there has been an unfortunate tendency to label all difficult to classify cases of excessive daytime sleepiness as idiopathic hypersomnia. At present due to the description of new disorders such as upper airway resistance syndrome, narcolepsy without cataplexy, delayed sleep phase syndrome, all of which were formerly confused with idiopathic hypersomnia and the clear identification of a "polysymptomatic" or "classic" form of idiopathic hypersomnia, the limits of the disorder become more precise. Still there are a number of cases of isolated excessive daytime sleepiness with no prolonged night sleep, no difficulty waking up, which lay between narcolepsy and genuine idiopathic hypersomnia. Thus there is a definite need to further develop laboratory investigations to help identify and classify these cases. Moreover pathophysiology and pathogenesis are still in their infancy and efforts have to be pursued in this direction. Treatment has not made consistent progress except for the use of a new wake promoting compound, modafinil, which has not yet been evaluated in controlled studies.

Journal Article↗
PubMed2005

Sleep and stroke.

More than 50% of stroke patients have sleep-disordered breathing (SDB), mostly in the form of obstructive sleep apnea (OSA). SDB represents both a risk factor and a consequence of stroke. The presence of SDB has been linked with poorer long-term outcome and increased long-term stroke mortality. Continuous positive airway presure is the treatment of choice for OSA. Oxygen and other forms of ventilation may be helpful in other (e.g., central) forms of SDB. SDB can improve spontaneously after stroke. About 20 to 40% of stroke patients have sleep-wake disorders (SWD), mostly in form of insomnia, excessive daytime sleepiness/fatigue, or hypersomnia (increased sleep needs). Depression, anxiety, SDB, stroke complications, and medications may contribute to SWD and should be addressed first therapeutically. Brain damage per se, often at thalamic or brainstem level, can be also a cause of persisting SWD. In these patients, hypnotics, dopeminergic agents, and stimulants (e.g., modafinil) can be attempted.

Humans↗
PubMed2006

Increased REM sleep associated with melatonin deficiency after pinealectomy: a case study.

The objectives of the investigation were to assess hypersomnia, which progressively appeared in a young patient after a pinealectomy, chemotherapy, and radiotherapy for a typical germinoma, as well as the potential benefit of melatonin administration in the absence of its endogenous secretion. 24 h ambulatory polysomnography and the Multiple Sleep Latency Test (MSLT) were performed; in addition, daily plasma melatonin, cortisol, growth hormone, prolactin, and rectal temperature profiles were determined before and during melatonin treatment (one 2 mg capsule given nightly at 21:00 h for 4 weeks). MSLT showed abnormal sleep latency and two REM sleep onsets. Nighttime total sleep duration was lengthened, mainly as a consequence of an increased REM sleep duration. These parameters were slightly modified by melatonin replacement. Plasma melatonin levels, which were constantly nil in the basal condition, were increased to supraphysiological values with melatonin treatment. The plasma cortisol profile showed nycthemeral variation within the normal range, and the growth hormone profile showed supplementary diurnal peaks. Melatonin treatment did not modify the secretion of either hormone. The plasma prolactin profile did not display a physiological nocturnal increase in the basal condition; however, it did during melatonin treatment, with the rise coinciding with the nocturnal peak of melatonin concentration. A 24 h temperature rhythm of normal amplitude was persistent, though the mean level was decreased and the rhythm was dampened during melatonin treatment. The role of radiotherapy on the studied parameters cannot be excluded; the findings of this case study suggest that the observed hypersomnia is not the result of melatonin deficiency alone. Overall, melatonin treatment was well tolerated, but the benefit on the sleep abnormality, especially on daytime REM sleep, was minor, requiring the re-introduction of modafinil treatment.

Adult↗