Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of caffeine in the evening produces poor sleep. Patients with insomnia have characteristic electrocardiogram (ECG) changes, including increased heart rate (HR), increased sympathetic activity, and decreased parasympathetic activity. Fifteen young adult normal subjects slept in the laboratory for several nights prior to randomization into a caffeine protocol where subjects received caffeine 400 mg 30 min prior to one night of sleep and placebo randomly prior to another night. ECG was sampled at a rate of 500 Hz and recorded onto a PC. Data samples of 256-s periods of the ECG trace were taken from wake (before sleep), stage II, and REM for placebo and caffeine conditions. A peak detection algorithm was used to identify the R-R intervals (in milliseconds) from the ECG. A common QT variability algorithm was used to find the QT interval for each beat using the time-stretch model. The powers for HR and QT series were integrated in the bands of LF (low frequency: 0.04-0.15 Hz) and HF (high frequency: 0.15-0.5 Hz) bands. There was a significant caffeine by sleep stage interaction for LF/HF ratios (F = 4.0; df = 2, 18; P = .04). LF/HF ratios were significantly higher during REM following caffeine administration. There was also a significant caffeine by sleep stage interaction for QTvi (QT variability normalized for mean QT interval divided by HR variability normalized for mean HR; F = 5.6; df = 2, 12; P = .02). QTvi was also significantly higher during REM following caffeine administration. The higher LF/HF ratios and QTvi during REM are most likely due to the sympathetic effects of caffeine. These findings suggest that excessive caffeine intake may result in adverse cardiovascular events in vulnerable subjects.
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PMID:Effects of caffeine on heart rate and QT variability during sleep. 1618 81

We described three cases of hypnic headache with successful treatment by lithium carbonate or caffeine. This is the first detail report of Japanese cases. An endocrinological test and rhythm analyses of ambulatory blood pressure (ABP) and heart rate variability in a case suggested possible association between hypnic headache and hypothalamic-pituitary dysfunction. Case 1: A 48-year-old female migraineur complained of new-onset nocturnal headaches. Her headache awakened her from sleep between 1 AM and 2 AM. The headache occurred 3-4 times per week and lasted from 1 hour to 2 hours. The headache were moderate intensity and bilateral dull throbbing pain that located in the forehead to temples. There was no accompanying symptoms such as nausea, phonophobia, photophobia, nor the other autonomic features including conjunctival injection or tearing during the headache attacks. Physical and neurological examinations showed normal results except slight weakness and mild dysesthesia of the left arm due to a vertebral disk herniation at C5/6 level. In the pituitary endocrinological test, the prolactin level remarkably increased in response to the TRH loading. The single cosinor analysis demonstrated significant circadian rhythm of ABP parameters. However, the analysis did not demonstrate any significant circadian rhythm of Holter ECG parameters of time domain analysis and frequency analysis. Receiving 200 mg lithium bicarbonate before sleep, her nocturnal headache completely disappeared. Case 2: A 68-year-old woman had been followed up by her chronic tension-type headache since her forties. At her 66-years, she suffered from a new nocturnal headache. She awoke from sleep by the headache about 3 AM and the headache lasted 30 min. Moderate, dull headache located on her left temple to parietal head, 3-4 times/week. She was able to go back asleep without any medication after spontaneous headache cessation. She first complained the nocturnal headache at the 10 months later of the new headache appearance. She received 200 mg caffeine just before sleep and her headache has been disappeared. Case 3: 70-year-old women had been regularly visited our clinics for her migraine and chronic tension-type headache. She received amitriptyline and her headaches was well controlled. At her 69 years, she complained nocturnal headache. It occured every other day. The headache was moderate pulsative dull pain on the occipital region and lasted 90 minutes without any autonomic symptoms. Headache began between midnight and 1 AM. She told us her new nocturnal headache one year later of the onset. Oral caffeine (200 mg) just before sleep did not improve her headache and caused insomnia. Receiving 100 mg lithium before sleep, her hypnic headache disappeared completely. These three cases are compatible with the diagnostic criteria proposed in ICHD-II. There were some patients with hypnic headache in Japan and neurologists should pay attentions to this form of benign headache, because some beneficial treatments are currently available.
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PMID:[Three Japanese cases of hypnic headache]. 1661 41

There is ample evidence for the existence of an association between sleeplessness and worry. Not much is known, however, concerning the nature of this relationship. Therefore, a study was conducted investigating the causal relationship between sleeplessness and nocturnal worry. A 2 x 2 (Worry x Induced sleeplessness) analysis of covariance design was used. The first factor consisted of a subject variable defined by scoring either high or low on a trait measure of worry (the Penn State Worry Questionnaire) and the second factor consisted of 300 mg caffeine or placebo. A total of 96 female undergraduate students participated. The dependent variables comprised measures of nocturnal worry (the Night-Time Thoughts Questionnaire) and subjective and objective sleep parameters. Overall, caffeine caused an increase in nocturnal worry and sleeplessness. A significant interaction effect occurred between Worry and Induced sleeplessness on one of the objective sleep parameters, but no other interaction effects were significant. The results suggest that worry may occur as an epiphenomenon of sleeplessness.
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PMID:Night-time thoughts in high and low worriers: reaction to caffeine-induced sleeplessness. 1694 54

More than 6 million Americans work night shifts on a regular or rotating basis. The negative consequences of shift work have been established, and recent evidence suggests that patients with shift work sleep disorder (SWSD) are at increased risk of these consequences and co-morbidities. SWSD is a relatively common but under-recognised, and hence undertreated, condition with potentially serious medical, social, economic and quality-of-life consequences. In addition to increased risk of gastrointestinal and cardiovascular disease, patients with SWSD experience clinically significant excessive sleepiness or insomnia associated with work during normal sleep times, which has important safety implications. A number of studies have evaluated countermeasures or interventions in shift workers; proposed treatments include chronobiotic interventions, such as light exposure, melatonin, hypnotic agents, caffeine and CNS stimulants (amphetamine), and the wake-promoting agents modafinil and armodafinil. However, most studies evaluating pharmacological therapies and nonpharmacological interventions simulate night-shift work under conditions that may not accurately reflect real-world activities. Pharmacological and nonpharmacological countermeasures evaluated mostly in simulated laboratory conditions have been shown to improve alertness or sleep in shift workers but have not yet been evaluated in patients with SWSD. To date, three randomised, double-blind clinical studies have evaluated pharmacological therapies in patients with SWSD. These studies showed that modafinil and armodafinil significantly improve the ability to sustain wakefulness during waking activities (e.g. working, driving), overall clinical condition, and sustained attention or memory in patients with SWSD. In conclusion, SWSD is a common condition that remains under-recognised and undertreated. Further research is needed to evaluate different treatment approaches for this condition, to clarify the substantial health and economic consequences of SWSD, and to determine the potential for interventions or treatments to reduce the negative consequences of this condition.
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PMID:Shift work sleep disorder: burden of illness and approaches to management. 1718 77

Ethanol and caffeine are two of the oldest human drugs. Their pervasive integration into the modern human diet may reflect behavioral attempts to correct maladaptations induced by evolutionary displacement of the autonomic system. The dietary adoption of caffeine may parallel the emergence of cognition as an independent basis of competition. Enhancement of the cognitive ability to gather and process information likely evolved as a valuable adjunct to physical behavior in prehistoric fight-or-flight encounters. Caffeine effectively exploits this pre-existing association between adrenergic activity and cognitive readiness, leading to its use in the modern environment where success in competition increasingly depends on cognitive, rather than physical, prowess. Ethanol may have emerged as a dietary means to buffer the maladaptive chronic sympathetic activation and fear response associated with stressful lifestyles and the social phobias associated with the dissolution of kin networks. We explore the health implications of ethanol and caffeine use, with particular attention to their acute and chronic effects on the autonomic axis. The putative protective effects of ethanol in surviving major trauma or reducing inflammation and heart disease may relate to tempering the behavioral and cardiovascular consequences of catastrophic or chronic sympathetic activation. Acute or chronic abuse of ethanol manifests paradoxical pro-adrenergic effects such as tremors and insomnia that may partly represent compensatory responses. Compensatory remodeling may also explain why confirmation of detrimental effects related to caffeine-induced sympathetic activation has proven elusive; indeed, paradoxical pro-vagal benefits may eventually be recognized. Ethanol and caffeine are potential agents that may beneficially expand the dynamic range of the autonomic system. In an environment where the Darwinian value of knowledge has increasingly supplanted that of physical traits, the consumption of caffeine and alcohol may represent both a cause and an effect of modern human evolution.
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PMID:Brewing controversies: Darwinian perspective on the adaptive and maladaptive effects of caffeine and ethanol as dietary autonomic modulators. 1719 16

ED managers should be aware of the tendency of young people to abuse caffeine and other nonprescription drugs. Experts say they end up in the ED more often than we think. Be sure to ask young patients with chest pain or heart palpitations whether they have taken any caffeine supplements. Be aware that most caffeine abusers also are abusing other pharmaceuticals such as dextramathorphan. Symptoms of caffeine abuse can include insomnia, tremors, sweating, nausea, vomiting, diarrhea, and neurological symptoms.
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PMID:Caffeine abuse may be missed in the ED. 1720 83

Caffeine is the most widely used stimulant in Western countries. Some people voluntarily reduce caffeine consumption because it impairs the quality of their sleep. Studies in mice revealed that the disruption of sleep after caffeine is mediated by blockade of adenosine A2A receptors. Here we show in humans that (1) habitual caffeine consumption is associated with reduced sleep quality in self-rated caffeine-sensitive individuals, but not in caffeine-insensitive individuals; (2) the distribution of distinct c.1083T>C genotypes of the adenosine A2A receptor gene (ADORA2A) differs between caffeine-sensitive and -insensitive adults; and (3) the ADORA2A c.1083T>C genotype determines how closely the caffeine-induced changes in brain electrical activity during sleep resemble the alterations observed in patients with insomnia. These data demonstrate a role of adenosine A2A receptors for sleep in humans, and suggest that a common variation in ADORA2A contributes to subjective and objective responses to caffeine on sleep.
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PMID:A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep. 1732 97

Our aim was to observe the induction of anxiety symptoms and panic attacks by a caffeine challenge test in panic disorder (PD) patients (DSM-IV) and their healthy first-degree relatives. We randomly selected 25 PD patients, 27 healthy first-degree relatives of probands with PD, and 22 healthy volunteers with no family history of PD. In a randomized double-blind experiment performed over two occasions 7 days apart, 480 mg caffeine and a caffeine-free solution were administered in a coffee form. Using specific panic attack criteria, 52.0% (n=13) PD patients, 40.7% (n=11) first-degree relatives (chi2=1.81, df=1, P=0.179), and none of the control subjects had a panic attack after the test (chi2=51.7, df=2, P<0.001). In this caffeine challenge test, PD patients and their first-degree relatives were more sensitive than healthy volunteers to the panic attack symptoms but less sensitive to headache, increase in blood pressure, and insomnia. Our data suggest that there is an association between panic attacks after the intake of 480 mg of caffeine in PD patients and their first-degree relatives. There is a clear differentiation of PD patients and their first-degree relatives by a caffeine test from the healthy group.
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PMID:A caffeine challenge test in panic disorder patients, their healthy first-degree relatives, and healthy controls. 1782 63

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

The infusion of flowers of several species of Citrus genera is used as a sedative to treat insomnia in Mexican traditional medicine. The aims of this study were to investigate the sedative effect of different extracts of flowers of Citrus sinensis (L.) Osbeck (Rutaceae) and describe the pharmacological action mechanism of the sedative active compounds of this plant. The methanol and dichloromethane extracts, obtained from the flowers of Citrus sinensis (L.) Osbeck (Rutaceae), showed a dose-dependent sedative effect in the exploratory cylinder model in mice, with ED50 (ip) values of 47.04+/-12.03 mg/kg and 129.15+/-21.25 mg/kg, respectively. Hesperidin (ED50=11.34+/-2.48 mg/kg) was identified in the methanol extract as the sedative active principle of this plant. The pre-treatment with atropine (1 mg/kg I. P.), flumazenil (2 mg/kg I. P.), clonidine (0.01 mg/kg I. P.), isoproterenol (0.3 mg/kg I. P.), haloperidol (0.3 mg/kg I. P.), WAY 100 635 (3 mg/kg I. P.), P-chlorophenylalanine (250 mg/kg I. P., twice per day for 2 days), forskolin (3 mg/kg I. P.) and rolipram (0.173 mg/kg I. P.) did not modify the sedative effect of 30 mg/kg hesperidin. However, the sedative effect of this compound was potentiated by yohimbine (1.25 mg/kg I. P.) and buspirone (1 mg/kg I. P.), and reverted by pretreatment with aminophylline (30 mg/kg I. P.), caffeine (30 mg/kg I. P.) and several doses of 1,3-dimethyl-8-phenylxanthine (10, 30 and 54.7 mg/kg I. P.). These results suggest that adenosine receptors might be involved in the sedative action of hesperidin, identified as the active principle of the flowers of Citrus sinensis.
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PMID:Pharmacological exploration of the sedative mechanism of hesperidin identified as the active principle of Citrus sinensis flowers. 1921 59


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