Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0037315 (sleep apnea)
 8,000 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventy-five patients meeting international diagnostic criteria for narcolepsy enrolled in a 6-week, three-period, randomized, crossover, placebo-controlled trial. Patients received placebo, modafinil 200 mg, or modafinil 400 mg in divided doses (morning and noon). Evaluations occurred at baseline and at the end of each 2-week period. Compared with placebo, modafinil 200 and 400 mg significantly increased the mean sleep latency on the Maintenance of Wakefulness Test by 40% and 54%, with no significant difference between the two doses. Modafinil, 200 and 400 mg, also reduced the combined number of daytime sleep episodes and periods of severe sleepiness noted in sleep logs. The likelihood of falling asleep as measured by the Epworth Sleepiness Scale was equally reduced by both modafinil dose levels. There were no effects on nocturnal sleep initiation, maintenance, or architecture, nor were there any effects on sleep apnea or periodic leg movements. Neither dose interfered with the patients' ability to nap voluntarily during the day nor with their quantity or quality of nocturnal sleep. Modafinil produced no changes in blood pressure or heart rate in either normotensive or hypertensive patients. The only significant adverse effects were seen at the 400-mg dose, which was associated with more nausea and more nervousness than either placebo or the 200-mg dose. As little as a 200-mg daily dose of modafinil is therefore an effective and well-tolerated treatment of excessive daytime somnolence in narcoleptic persons.
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PMID:Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy. 927 May 75

Narcolepsy is a disabling, chronic sleep-wake disorder that typically starts in a patient's second or third decade of life. Its key features are hypersomnia and cataplexy. Sleep paralysis, hallucinations, and disrupted sleep are nonspecific symptoms and are not always present. Disability relates primarily to sleepiness- related cognitive impairment, accidents, and psychosocial problems. Treatment, which includes counseling, scheduled napping, and pharmacologic intervention, is effective for most patients. Hypersomnia is best treated with such indirect sympathomimetics as mazindol, pemoline, methylphenidate, and amphetamine. Modafinil may become the drug of choice because it has fewer side effects. Cataplexy, sleep paralysis, and hallucinations may be ameliorated by compounds, including clomipramine and imipramine, that suppress rapid eye movement (REM) sleep. Regular follow-up visits enable the clinician to recognize uncommon but serious side effects (tolerance, substance abuse, psychosis, and hypertension) and additional sleep disturbances (sleep apnea, periodic limb movements in sleep, REM sleep behavior disorder), which can be specifically treated.
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PMID:Narcolepsy. 1109 16

Some patients with the sleep apnea/hypopnea syndrome (SAHS) remain subjectively and objectively sleepy despite using effective continuous positive airway pressure (CPAP) therapy. The aim of this single center study was to determine the efficacy and safety of the novel wake-promoting medication modafinil in the treatment of CPAP-resistant daytime sleepiness. Thirty sleep apneics receiving effective CPAP therapy (objective use, 6.5 +/- 1.1 h/night) received daily single doses of 400 mg modafinil or placebo for 2 wk in a double-blind randomized crossover design. Outcome measures were assessed at baseline and at the end of both 2-wk treatment periods. Treatment periods were separated by a 1-wk washout. Modafinil had no effect on sleepiness as measured by the Epworth Sleepiness Scale or the Multiple Sleep Latency Test (p > 0.1); however, significant improvements in alertness were found with the Maintenance of Wakefulness Test (modafinil 18.3 +/- 3.9 min; placebo, 16.6 +/- 5.0 min; p < 0.02). No significant treatment-related improvements in cognitive performance or quality of life were found with modafinil (all p > 0.05). There was a significant reduction in CPAP use on modafinil compared to placebo (6.3 +/- 1 h/ night; 6.5 +/- 1, p = 0.03). This study suggests that modafinil may improve some aspects of alertness in patients with SAHS who remain sleepy during CPAP therapy, but further studies are required to assess the significance of the reduction in CPAP use.
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PMID:Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of residual excessive daytime sleepiness in the sleep apnea/hypopnea syndrome. 1128 66

Narcolepsy is a life-long central nervous system (CNS) syndrome characterised by excessive sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disturbed night-time sleep. Unsuccessfully treated narcolepsy confers increased risks on patients and on society due to the patient's increased chance of becoming involved in vehicle crashes and workplace mishaps. The syndrome may be diagnosed by a clinical history positive for cataplexy and excessive daytime sleepiness and negative for other more common sleep disorders such as sleep apnoea and sleep deprivation. Night-time polysomnography and multiple sleep latency testing are helpful in differentiating narcolepsy from other sleep problems. Recent data from canine, murine, and human forms of narcolepsy indicate that genetically or developmentally mediated deficits in the hypocretin neurotransmitter system may cause some, but not all, forms of narcolepsy. Pharmacotherapy for narcolepsy is required to control symptoms and involves the use of CNS stimulants or modafinil to control sleepiness and antidepressant medications or sodium oxybate to control cataplexy. Modafinil and sodium oxybate have been developed and approved specifically for the indication of narcolepsy based on large, double-blind, placebo-controlled, parallel group efficacy and safety studies. The efficacy of drugs in the treatment of narcolepsy is variable from patient to patient and usually associated with adverse effects that can limit patient compliance and, therefore, symptom control. Nevertheless, the benefits of pharmacotherapy are judged to outweigh the risks to the patient. The favourable benefit-risk ratio of pharmacotherapy is greater if one considers the reduced risk to society of vehicle crashes and workplace mishaps that might be precipitated by attentional lapses or sleep attacks in the untreated or under-treated patient with narcolepsy.
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PMID:Benefits and risks of pharmacotherapy for narcolepsy. 1222 90

Patients with myotonic dystrophy frequently suffer from excess daytime sleepiness, which can be a significant cause of disability. Previous studies have indicated that this excess daytime sleepiness is only occasionally due to obstructive sleep apnoea and may be principally of central nervous system origin. Modafinil has been successfully used to treat narcolepsy, a central disorder causing excess daytime sleepiness. We have investigated the use of this drug in myotonic dystrophy patients with excess daytime sleepiness. Patients were recruited from a clinic population on the basis of screening with the Epworth Sleepiness Scale. Patients scoring 10 and above were invited to participate in a randomized double-blind crossover trial of modafinil versus placebo, with four weeks in each arm of the study separated by a 2-week washout period. Patients were assessed by polysomnography at baseline. The primary outcome measures were change in both the Epworth Sleepiness Scale and a modified Maintenance of Wakefulness Test, which were measured at the start of each arm of the trial and in week 3 of each intervention period. In agreement with previous smaller studies, sleepiness is not correlated with CTG expansion size. Treatment with modafinil showed a non-significant reduction in median Epworth Sleepiness Scale. However, the median Maintenance of Wakefulness Test score was prolonged by treatment (31.7-40 min, P=0.006). There were no significant adverse cardiac effects of the drug in this group of patients (resting 12 lead and 24 h ECG monitoring). Selected patients with myotonic dystrophy and excess daytime sleepiness may benefit from modafinil. In this patient group the Epworth Sleepiness Scale may not be the most reliable measure of sleepiness. Despite the potential for cardiac disease in these patients, the drug was well tolerated with no adverse effects.
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PMID:Reduction in excess daytime sleepiness by modafinil in patients with myotonic dystrophy. 1279 91

In January 2004, the wake-promoting agent, modafinil, was approved in the US for the treatment of excessive sleepiness (ES) associated with obstructive sleep apnoea/hypopnoea syndrome (OSAHS) and shift-work sleep disorder (SWSD), representing an expansion of its labelling from the initial indication for ES associated with narcolepsy. A total of five randomised, placebo-controlled studies in these three disorders showed statistically significant benefits on various objective measures and subjective estimates of ES, including the Multiple Sleep Latency Test, Maintenance of Wakefulness Test, Epworth Sleepiness Scale and Karolinska Sleepiness Scale. Significant improvement was also seen in overall clinical condition (on the Clinical Global Impression of Change) and measures of sustained attention and reaction time (on the Psychomotor Vigilance Task). The clinical efficacy of modafinil, combined with improved safety over CNS stimulants, has made it the most prescribed medication for the treatment of ES associated with narcolepsy. Modafinil is the only medication approved for ES associated with OSAHS and SWSD (for OSAHS, it is indicated as an adjunct to standard treatments for the under-lying obstruction). Unlike many other medications used for ES, modafinil is not known to be abused. The most common adverse event reported in clinical studies was headaches; most were transient and mild-to-moderate in severity. Modafinil also has the potential for interactions with other drugs metabolised via cytochrome P450 enzyme pathways. Potential obstacles to the use of modafinil include an under-recognition of ES and its consequences. Increased education, both of the public and the medical community, should improve the recognition and therapy of ES.
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PMID:Modafinil: new indications for wake promotion. 1570 89

Excessive daytime sleepiness (EDS) is a common and debilitating symptom of narcolepsy and other sleep disorders. Modafinil is a novel stimulant which effectively treats EDS, yet lacks many of the undesirable side-effects commonly encountered with currently available compounds. The specific mode of action of modafinil is not well understood, but it may promote sleep by indirectly influencing adrenergic or GABAergic neurotransmission. Modafinil-induced wakefulness is not associated with rebound hypersomnolence or the potential for abuse as is often encountered with other stimulants such as amphetamines. At typical therapeutic doses, modafinil may produce dry mouth but generally has a low incidence of minor side-effects. Many preclinical and clinical studies have demonstrated the effectiveness of modafinil in promoting wakefulness and vigilance in normal subjects and in those with EDS. Modafinil significantly improves the EDS of narcolepsy and also may improve the EDS of idiopathic hypersomnia and obstructive sleep apnoea. Modafinil's low prevalence of side-effects, minimal potential for abuse, and lack of rebound hypersomnia indicate that it has potential to become a widely prescribed drug for the treatment of narcolepsy.
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PMID:Modafinil: a novel stimulant for the treatment of narcolepsy. 1599 23

Modafinil (Provigil is a wake-promoting agent that is pharmacologically distinct from CNS stimulants, such as amfetamine, dexamfetamine and methylphenidate. Modafinil is approved for use in the US and certain European countries for use in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnoea/hypopnoea syndrome (OSA/HS) or shift work sleep disorder (SWSD). Oral modafinil promotes wakefulness in patients with OSA/HS and SWSD. It is an effective adjunctive therapy in patients with residual excessive sleepiness associated with OSA/HS who are receiving nasal continuous positive airway pressure (nCPAP) therapy. In SWSD, the drug improves night-time wakefulness without disrupting daytime sleep. Modafinil is generally well tolerated in patients with OSA/HS or SWSD and has a low abuse potential. Thus, modafinil is a valuable new treatment option for use in patients with excessive sleepiness associated with OSA/HS (as an adjunct to nCPAP) or SWSD.
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PMID:Modafinil : a review of its use in excessive sleepiness associated with obstructive sleep apnoea/hypopnoea syndrome and shift work sleep disorder. 1614 93

(1) The first-line treatment for patients with troublesome obstructive sleep apnoea syndrome is night-time nasal continuous positive airway pressure, which reduces daytime drowsiness and improves cognitive performance. (2) Modafinil, a non amphetamine psychostimulant already marketed for idiopathic narcolepsy and hypersomnia, is the first drug to be approved in France for the treatment of patients with residual daytime drowsiness despite nasal continuous positive airway pressure treatment. (3) Clinical evaluation of modafinil for this indication consists of two short-term double-blind placebo-controlled trials, lasting 4 and 12 weeks, and including a total of about 500 patients. At a dose of 400 mg/day, 68% of patients experienced an improvement in their daytime drowsiness (usually partial), compared to 37% of patients on placebo. It is not known how many patients no longer had any daytime drowsiness. A major improvement occurred in about 14% of patients (7% on placebo). (4) The main adverse effects of modafinil are neuropsychological (headache, nervousness, insomnia, anxiety, nausea). (5) In short, modafinil is an option to consider when continuous positive airway pressure is not sufficiently effective and when drowsiness continues to significantly interfere with daily activities. However, it only appears to provide a major benefit to about 10% of patients. The only important improvement is in daytime drowsiness, and this is often offset by adverse effects such as headache. Effects of long-term treatment are not known.
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PMID:Modafinil: new indication. For a minority of patients with sleep apnoea. 1758 24

Modafinil is a wake-promoting agent that is pharmacologically different from other stimulants. It has been investigated in healthy volunteers, and in individuals with clinical disorders associated with excessive sleepiness, fatigue, impaired cognition and other symptoms. This review examines the use of modafinil in clinical practice based on the results of randomized, double-blind, placebo-controlled clinical trials available in the English language in the MEDLINE database. In sleep-deprived individuals, modafinil improves mood, fatigue, sleepiness and cognition to a similar extent as caffeine but has a longer duration of action. Evidence for improved cognition in non-sleep-deprived healthy volunteers is controversial.Modafinil improves excessive sleepiness and illness severity in all three disorders for which it has been approved by the US FDA, i.e. narcolepsy, shift-work sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure (CPAP). However, its effects on safety on the job and on morbidities associated with these disorders have not been ascertained. Continued use of CPAP in obstructive sleep apnoea is essential. Modafinil does not benefit cataplexy.In very small, short-term trials, modafinil improved excessive sleepiness in patients with myotonic dystrophy. It was efficacious in fairly large studies of attention deficit hyperactivity disorder (ADHD) in children and adolescents, and was as efficacious as methylphenidate in a small trial, but has not been approved by the FDA, in part because of its serious dermatological toxicity. In a trial of 21 non-concurrent subjects, with 2-week treatment periods, modafinil was as effective as dexamfetamine in adult ADHD. Modafinil was helpful for depressive symptoms in bipolar disorder in a trial that excluded patients with stimulant-induced mania. A single dose of modafinil may hasten recovery from general anaesthesia after day surgery. A single dose of modafinil improved the ability of emergency room physicians to attend didactic lectures after a night shift, but did not improve their ability to drive home and caused sleep disturbances subsequently.Modafinil had a substantial placebo effect on outcomes such as fatigue, excessive sleepiness and depression in patients with traumatic brain injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple sclerosis; however, it did not provide any benefit greater than placebo.Trials of modafinil for excessive sleepiness in Parkinson's disease, cocaine addiction and cognition in chronic fatigue syndrome provided inconsistent results; all studies had extremely small sample sizes. Modafinil cannot be recommended for these conditions until definitive data become available.Modafinil induces and inhibits several cytochrome P450 isoenzymes and has the potential for interacting with drugs from all classes. The modafinil dose should be reduced in the elderly and in patients with hepatic disease. Caution is needed in patients with severe renal insufficiency because of substantial increases in levels of modafinil acid. Common adverse events with modafinil include insomnia, headache, nausea, nervousness and hypertension. Decreased appetite, weight loss and serious dermatological have been reported with greater frequency in children and adolescents, probably due to the higher doses (based on bodyweight) used. Modafinil may have some abuse/addictive potential although no cases have been reported to date.
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PMID:Approved and investigational uses of modafinil : an evidence-based review. 1872 34


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