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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A specially-designed time-varying magnetic field was developed to treat insomnia. Clinical results showed that this method could shorten the time to go to sleep and prolong the sleep duration. However, the mechanism of this method is still not well understood. In this study, the effect of magnetic stimulation on the release of serotonin (5-HT), noradrenaline (NE), dopamine (DA) in raphe nuclei of rats, which are known to play an important role in the sleep-wake regulation, was investigated. It was shown that there was a significant difference in the release of serotonin between control group and experimental group (p<0.01). The release of serotonin of the experimental group increased significantly. No obvious release changes of NE and DA are found (p>0.05). The results indicates that one possible mechanism of inducing sleep using specially designed magnetic field is to change the release of sleep-related neurotransmitters.
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PMID:Influence of time-varying magnetic field on the release of neurotransmitters in raphe nuclei of rats. 1728 85

Through a highly divergent efferent projection system, the locus coeruleus-noradrenergic system supplies norepinephrine throughout the central nervous system. State-dependent neuronal discharge activity of locus coeruleus neurons has long-suggested a role of this system in the induction of an alert waking state. More recent work supports this hypothesis, demonstrating robust wake-promoting actions of the locus coeruleus-noradrenergic system. Norepinephrine enhances arousal, in part, via actions of beta- and alpha1-receptors located within multiple subcortical structures, including the general regions of the medial septal area and the medial preoptic areas. Recent anatomical studies suggest that arousal-enhancing actions of norepinephrine are not limited to the locus coeruleus system and likely include the A1 and A2 noradrenergic cell groups. Thus, noradrenergic modulation of arousal state involves multiple noradrenergic systems acting within multiple subcortical regions. Pharmacological studies indicate that the combined actions of these systems are necessary for the sustained maintenance of arousal levels associated with spontaneous waking. Enhanced arousal state is a prominent aspect of both stress and psychostimulant drug action and evidence indicates that noradrenergic systems likely play an important role in both stress-related and psychostimulant-induced arousal. These and other observations suggest that the dysregulation of noradrenergic neurotransmission could well contribute to the dysregulation of arousal associated with a variety of behavioral disorders including insomnia and stress-related disorders.
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PMID:Noradrenergic modulation of arousal. 1819 83

To clarify the profile of depressive symptoms in major depressive episodes in patients with Alzheimer's disease (AD-MD), we compared AD-MD with major depressive disorder in non-demented elderly patients (MDD) matched for age, using the 17-item Hamilton Rating Scale for Depression (HAM-D(17)). In addition, to clarify which depressive symptoms of AD patients respond to treatment with the selective serotonin and noradrenaline reuptake inhibitor (SNRI) milnacipran, we compared the HAM-D(17) average score and the score of each HAM-D item, the mini-mental state examination (MMSE) score, and GAF score according to the DSM-IV evaluation of AD-MD patients at baseline and at the endpoint (12 weeks). Depressive mood, loss of interest in hobbies and social activities and anxiety (psychic) scored the highest in both AD-MD and MDD groups, while psychomotor retardation scored significantly higher in AD-MD, and insomnia and anxiety (somatic) significantly did so in MDD. We also found that depressive mood, suicidal tendency, loss of interest, psychomotor retardation, anxiety (psychic), gastrointestinal symptoms, general somatic symptoms, and hypochondriasis remarkably improved in patients of AD-MD treated with milnacipran. Our results suggest that in general the profiles of depression in AD-MD and MDD are similar, despite some different clinical features between both conditions. Our study also suggests that milnacipran is promising to treat a broad range of depressive symptoms in AD-MD patients.
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PMID:Therapeutic effects of the selective serotonin noradrenaline reuptake inhibitor milnacipran on depressive symptoms in patients with Alzheimer's disease. 1916 99

Atomoxetine (Strattera(R)) is a selective norepinephrine (noradrenaline) reuptake inhibitor that is not classified as a stimulant, and is indicated for use in patients with attention-deficit hyperactivity disorder (ADHD). Atomoxetine is effective and generally well tolerated. It is significantly more effective than placebo and standard current therapy and does not differ significantly from or is noninferior to immediate-release methylphenidate; however, it is significantly less effective than the extended-release methylphenidate formulation OROS(R) methylphenidate (hereafter referred to as osmotically released methylphenidate) and extended-release mixed amfetamine salts. Atomoxetine can be administered either as a single daily dose or split into two evenly divided doses, has a negligible risk of abuse or misuse, and is not a controlled substance in the US. Atomoxetine is particularly useful for patients at risk of substance abuse, as well as those who have co-morbid anxiety or tics, or who do not wish to take a controlled substance. Thus, atomoxetine is a useful option in the treatment of ADHD in children and adolescents. The mechanism of action of atomoxetine is unclear, but is thought to be related to its selective inhibition of presynaptic norepinephrine reuptake in the prefrontal cortex. Atomoxetine has a high affinity and selectivity for norepinephrine transporters, but little or no affinity for various neurotransmitter receptors. Atomoxetine has a demonstrated ability to selectively inhibit norepinephrine uptake in humans and animals, and studies have shown that it preferentially binds to areas of known high distribution of noradrenergic neurons, such as the fronto-cortical subsystem. Atomoxetine was generally associated with statistically, but not clinically, significant increases in both heart rate and blood pressure in pediatric patients with ADHD. While there was an initial loss in expected height and weight among atomoxetine recipients, this eventually returned to normal in the longer term. Data suggest that atomoxetine is unlikely to have any abuse potential. Atomoxetine appeared less likely than methylphenidate to exacerbate disordered sleep in pediatric patients with ADHD. Atomoxetine is rapidly absorbed, and demonstrates dose-proportional increases in plasma exposure. It undergoes extensive biotransformation, which is affected by poor metabolism by cytochrome P450 (CYP) 2D6 in a small percentage of the population; these patients have greater exposure to and slower elimination of atomoxetine than extensive metabolizers. Patients with hepatic insufficiency show an increase in atomoxetine exposure. CYP2D6 inhibitors, such as paroxetine, are associated with changes in atomoxetine pharmacokinetics similar to those observed among poor CYP2D6 metabolizers. Once- or twice-daily atomoxetine was effective in the short-term treatment of ADHD in children and adolescents, as observed in several well designed placebo-controlled trials. Atomoxetine also demonstrated efficacy in the longer term treatment of these patients. A single morning dose was shown to be effective into the evening, and discontinuation of atomoxetine was not associated with symptom rebound. Atomoxetine efficacy did not appear to differ between children and adolescents. Stimulant-naive patients also responded well to atomoxetine treatment. Atomoxetine did not differ significantly from or was noninferior to immediate-release methylphenidate in children and adolescents with ADHD with regard to efficacy, and was significantly more effective than standard current therapy (any combination of medicines [excluding atomoxetine] and/or behavioral counseling, or no treatment). However, atomoxetine was significantly less effective than osmotically released methylphenidate and extended-release mixed amfetamine salts. The efficacy of atomoxetine did not appear to be affected by the presence of co-morbid disorders, and symptoms of the co-morbid disorders were not affected or were improved by atomoxetine administration. Health-related quality of life (HR-QOL) appeared to be positively affected by atomoxetine in both short- and long-term studies; atomoxetine also improved HR-QOL to a greater extent than standard current therapy. Atomoxetine was generally well tolerated in children and adolescents with ADHD. Common adverse events included headache, abdominal pain, decreased appetite, vomiting, somnolence, and nausea. The majority of adverse events were mild or moderate; there was a very low incidence of serious adverse events. Few patients discontinued atomoxetine treatment because of adverse events. Atomoxetine discontinuation appeared to be well tolerated, with a low incidence of discontinuation-emergent adverse events. Atomoxetine appeared better tolerated among extensive CYP2D6 metabolizers than among poor metabolizers. Slight differences were evident in the adverse event profiles of atomoxetine and stimulants, both immediate- and extended-release. Somnolence appeared more common among atomoxetine recipients and insomnia appeared more common among stimulant recipients. A black-box warning for suicidal ideation has been published in the US prescribing information, based on findings from a meta-analysis showing that atomoxetine is associated with a significantly higher incidence of suicidal ideation than placebo. Rarely, atomoxetine may also be associated with serious liver injury; postmarketing data show that three patients have had liver-related adverse events deemed probably related to atomoxetine treatment. Treatment algorithms involving the initial use of atomoxetine appear cost effective versus algorithms involving initial methylphenidate (immediate- or extended-release), dexamfetamine, tricyclic antidepressants, or no treatment in stimulant-naive, -failed, and -contraindicated children and adolescents with ADHD. The incremental cost per quality-adjusted life-year is below commonly accepted cost-effectiveness thresholds, as shown in several Markov model analyses conducted from the perspective of various European countries, with a time horizon of 1 year.
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PMID:Atomoxetine: a review of its use in attention-deficit hyperactivity disorder in children and adolescents. 1944 48

Venlafaxine is a serotonin-noradrenaline reuptake inhibitor (SNRI) that has no affinity for muscarinic, adrenergic or histaminergic receptors. In short-term trials, the adverse effects that occurred more often with venlafaxine than with placebo included nausea, somnolence, dizziness, dry mouth, and sweating. Rapid titration of the dose of venlafaxine to higher levels appeared, not unexpectedly, to be associated with an increased incidence of side effects. Side effects that appeared to be dose related included insomnia, nausea and sexual dysfunction. The incidence of nausea and dizziness was highest during the first 2 or 3 weeks of therapy and decreased rapidly thereafter. Somnolence also decreased over time. At high doses blood pressure increases were reported in a small percent of patients on venlafaxine and antidepressant drugs but were uncommon at the venlafaxine dose of 75-150 mg daily. Studies with venlafaxine in healthy volunteers indicate a low potential for drug-drug interactions. Overdoses have been reported in 14 of 3,082 patients administered venlafaxine in clinical trials, and no deaths were reported among these patients. Overdoses of venlafaxine induced mainly drowsiness and lethargy.
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PMID:Neurobiologic basis of antidepressant safety profiles. 1969 84

The function and dysfunction of the central noradrenergic system were reviewed together with the implications for the pathophysiological understanding of functional psychosis. Like the peripheral noradrenergic system, the central noradrenergic system plays a pivotal role in fight/flight reactions and stress. Overactivity of the system induces not only a sympathotonic state but also hyperarousal accompanied by insomnia, anxiety, irritability, emotional instability, paranoia, and excitation. On the other hand, its underactivity lowers the sympathetic tone and arousal level, resulting in hypersomnia, blunted responsiveness, or apathy. It has been confirmed in animal experiments that excess stress causes dysfunctions of the central noradrenergic system as a result of compensation, such as the overutilization-induced oversynthesis of noradrenaline. Dysfunction of the system, particularly its overactivity, plays an important role in various functional psychoses such as anxiety disorder, schizophrenia, and mood disorder, as well as behavioral and psychological symptoms of dementia (BPSD). Pharmacologically, the sedative effect of minor and major tranquilizers on hyperarousal is mediated by their action as noradrenaline antagonists. Some antidepressants potentiate noradrenergic activity, and should be used carefully in hyperaroused depressive patients. Thus, clinical evaluation of the central noradrenergic pathophysiology will provide us with information related to arousal to advance our understanding and treatment of functional psychoses.
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PMID:[Central noradrenergic system in psychiatry]. 1982 61

Bupropion, a noradrenaline/dopamine reuptake inhibitor, and venlafaxine, a serotonin/noradrenaline reuptake inhibitor, are both established antidepressants with proven efficacy in randomized controlled clinical trials. The objective of this double-blind, randomized, placebo- and active-controlled, eight-week, flexible-dose study was to evaluate the efficacy and tolerability of the once-daily extended-release formulations of these two antidepressants compared with placebo. Patients with major depressive disorder were randomized to once-daily treatment with bupropion XR 150 mg (n = 204), the extended-release formulation of venlafaxine (venlafaxine XR) 75 mg (n = 198) or placebo (n = 189) during weeks 1 to 4, with the option to double the dose at week 5 if response was inadequate. In this study, bupropion XR did not demonstrate statistically significant evidence of greater improvement from baseline compared with placebo on week 8 Montgomery Asberg Depression Rating scale scores (primary endpoint) or on secondary endpoints including CGI, HAM-A and responder and remitter analyses. Descriptive statistics for venlafaxine XR indicated separation versus placebo on MADRS total scores at week 8 and other intermediate time points, and on other endpoints including CGI, HAM-A and responder and remitter analyses. Both active treatments elicited improvement on the Sheehan Disability Scale and its subscales and were generally well tolerated at the doses studied. Rates of nausea, dry mouth, dizziness, hyperhidrosis, insomnia, constipation, tremor, anorexia and male sexual dysfunction were elevated in the venlafaxine XR group, consistent with its mixed serotonergic/noradrenergic mechanism. Rates of dry mouth, insomnia and hyperhidrosis were elevated in the bupropion XR group, consistent with its catecholaminergic mechanism.
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PMID:Double-blind, placebo-controlled comparison of the antidepressant efficacy and tolerability of bupropion XR and venlafaxine XR. 1993 70

Fibromyalgia is a chronic pain disorder characterized by widespread pain, stiffness, insomnia, fatigue and distress. Several randomized controlled trials (RCTs) have shown moderate effectiveness of pharmacological therapies for fibromyalgia pain. Evidence from these trials suggests that pharmacological therapy can not only improve pain but also fatigue, function and well-being in patients with fibromyalgia. Duloxetine and milnacipran, two highly selective serotonin-norepinephrine (noradrenaline) reuptake inhibitors, and the alpha(2)delta agonist pregabalin have been approved by the US FDA for the treatment of fibromyalgia symptoms. In general, about half of all treated patients seem to experience a 30% reduction of symptoms, suggesting that many patients with fibromyalgia will require additional therapies. Thus, other forms of treatment, including exercise, cognitive behavioural therapies and self-management strategies, may be necessary to achieve satisfactory treatment outcomes. Despite promising results of pilot trials, RCTs with dopamine receptor agonists and sodium channel antagonists have so far been disappointing for patients with fibromyalgia. However, new pharmacological approaches for the treatment of fibromyalgia pain and insomnia using sodium oxybate appear to be promising.
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PMID:Pharmacological treatment of fibromyalgia syndrome: new developments. 2003 Apr 22

The nature of the noradrenergic dysregulation in clinical anxiety disorders remains unclear. In panic disorder, the predominant view has been that central noradrenergic neuronal networks and/or the sympathetic nervous system was normal in patients at rest, but hyper-reactive to specific stimuli, for example carbon dioxide. These ideas have been extended to other anxiety disorders, which share with panic disorder characteristic subjective anxiety and physiological symptoms of excess sympathetic activity. For example, Generalized Anxiety Disorder is characterized by chronic free-floating anxiety, muscle tension, palpitation and insomnia. It has been proposed that there is chronic central hypersecretion of noradrenaline in Generalized Anxiety Disorder, with consequent hyporesponsiveness of central post-synaptic receptors. With regards to other disorders, it has been suggested that there is noradrenergic involvement or derangement, but a more specific hypothesis has not been enunciated. This paper reviews the evidence for noradrenergic dysfunction in anxiety disorders, derived from indirect measures of noradrenergic function in clinical populations.
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PMID:The role of central noradrenergic dysregulation in anxiety disorders: evidence from clinical studies. 2053 May 86

Duloxetine is a balanced and potent serotonin and noradrenaline reuptake inhibitor (SNRI) and has adverse effects that are commonly associated with such drugs, including nausea, dry mouth, constipation, insomnia, and dizziness. Recently, duloxetine-induced liver injury has also been observed in patients with preexisting liver disease or chronic alcohol use. We investigated the effects of duloxetine in a healthy young adult with major depressive disorder (MDD) but no risk factors, and found that his total bilirubin level increased to 3.3 mg/dL and he developed jaundice after 5 months of duloxetine treatment. Discontinuation of duloxetine treatment saw his total bilirubin level decrease to 1.8 mg/dL. Thus, the administration of duloxetine might induce liver injury in a patient with MDD. However, the limitations of this single case report must be acknowledged. Although the cause of hepatic dysfunction in this case remains to be elucidated, clinicians should monitor liver function carefully after duloxetine treatment. Further investigations with a larger sample are needed.
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PMID:Cholestatic jaundice induced by duloxetine in a patient with major depressive disorder. 2092 14


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