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)

The clinical trial development programme of mirtazapine (Org 3770), performed in Europe and the United States, demonstrated an outstanding safety profile of this compound. The evaluation of the safety was based on data from all patients who took at least one dose of study medication during studies comparing mirtazapine with placebo, amitriptyline or other active comparators. A general indication of mirtazapine's safety is the significantly lower percentage of patients (65%) who complained of any adverse clinical experiences compared with the placebo- (76%) or amitriptyline-treated group (87%). Moreover, drop-out rates due to adverse clinical experiences were significantly lower than in the amitriptyline-treatment group. Mirtazapine has virtually no anticholinergic, adrenergic or typical selective serotonin reuptake inhibitor (SSRI) side effects. The only significantly higher incidences versus placebo were seen in the adverse clinical effects of drowsiness (23% versus 14%), excessive sedation (19% versus 5%), dry mouth (25% versus 16%), increased appetite (11% versus 2%) and weight increase (10% versus 1%). These complaints were typically mild and transient in nature, and decreased over time despite increased doses of mirtazapine. In contrast, significantly higher incidences of headache (5% versus 10%) and weight decrease (2% versus 6%), symptoms commonly seen in depressed patients, were recorded in the placebo-treated patients. Also, typical SSRI adverse events, such as nausea, vomiting, diarrhoea and insomnia, and symptoms of sexual dysfunction were registered less frequently in mirtazapine-treated patients than in the placebo-treated patients. Approximately 10% of the mirtazapine-treated patients in the clinical trial programme were older than 65 years. The pattern of adverse clinical experiences seen in this group of patients is fully in line with that seen in the overall patient population. The analysis of vital sign indices, i.e. blood pressure and heart rate, showed that no changes occurred with mirtazapine treatment; this pattern was fully comparable to that seen with placebo. Furthermore, very low incidences of clinically relevant changes in laboratory indices, such as the liver enzymes alanine aminotransferase and aspartate aminotransferase or neutropenia, were recorded in each treatment group. Mirtazapine has a very low seizure-inducing potential: only one case was recorded in a patient with a history of seizures during previous treatment with clomipramine. The low seizure-inducing potential combined with a lack of cardiotoxic properties allows safety in an overdose of mirtazapine, even in elderly patients. The only symptom seen in the patients taking an overdose of mirtazapine alone or in combination with other drugs was excessive but transient somnolence, which resolved spontaneously within a few hours. In conclusion, the new antidepressant mirtazapine offers clinicians a unique combination of strong efficacy and good safety.
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PMID:Safety of mirtazapine: a review. 893 8

The objective of this study was to assess the psychiatric effects of the antiepileptic drug (AED) felbamate (FBM) in patients with epilepsy. FBM is a new AED with a novel putative (antiglutaminergic) mechanism. Older AEDs such as carbamazepine and valproate have psychotropic properties, but the psychiatric effects of FBM and other new antiglutamatergic AEDs remain to be determined. Thirty inpatients with refractory epilepsy were openly tapered off all AEDs in conjunction with intensive presurgical monitoring prior to a two week randomized double-blind parallel trial of FBM monotherapy versus placebo, followed by open FBM therapy. Psychopathology was rated with weekly psychiatric rating scales. Anxiety, depression and seizures increased significantly with AED discontinuation. Acute blind FBM monotherapy yielded antiepileptic and stimulant-like effects (insomnia, anorexia, and anxiety), but failed to influence AED withdrawal-emergent psychopathology. Restarting original AEDs resolved such pathology in FBM drop outs. Chronic open FBM also had stimulant-like effects, with half of the patients displaying psychiatric deterioration and the other half modest improvement compared to baseline therapies. Baseline insomnia and anxiety may be markers for poorer psychiatric responses to chronic open FBM. FBM had stimulant-like effects, lacked anxiolytic effects, and failed to attenuate AED withdrawal-emergent psychopathology. Baseline insomnia or anxiety may predict poorer psychiatric responses to FBM. Further studies are required to assess whether the novel psychiatric effects observed with FBM also occur with other new antiglutamatergic AEDs.
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PMID:Felbamate monotherapy has stimulant-like effects in patients with epilepsy. 896 74

Mirtazapine is a unique antidepressant that refines the specificity of effects on noradrenergic and serotonergic systems. It is an antagonist of presynaptic alpha 2-adrenergic autoreceptors and heteroreceptors on both norepinephrine and serotonin (5-HT) presynaptic axons, plus is a potent antagonist of postsynaptic 5-HT2 and 5-HT3 receptors. The net outcome of these effects is increased noradrenergic activity together with specific increased serotonergic activity, especially at 5-HT1A receptors. This mechanism of action maintains equivalent antidepressant efficacy but minimizes many of the adverse effects common to both tricyclic antidepressants and selective serotonin reuptake inhibitors. Mirtazapine has an onset of clinical effect in 2-4 weeks similar to other antidepressants, although sleep disturbances and anxiety symptoms may improve in the first week of treatment. It has minimal cardiovascular and anticholinergic effects, and essentially lacks serotonergic effects such as gastrointestinal symptoms, insomnia, and sexual dysfunction. Sedation, increased appetite, and weight gain are more common with mirtazapine than with placebo. An elimination half-life of 20-40 hours enables once-daily bedtime dosing. The recommended initial dosage is 15 mg once/day at bedtime, with an effective daily dosage range of 15-45 mg. Cases of overdose of up to 975 mg caused significant sedation but no cardiovascular or respiratory effects or seizures.
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PMID:Mirtazapine: an antidepressant with noradrenergic and specific serotonergic effects. 901 62

Gamma-hydroxybutyrate (GHB) is a compound found in mammalian brain which meets many criteria of a neurotransmitter. GHB has been investigated as a tool for inducing absence (petit mal) seizures, for use as an anesthetic, and for treatment of narcolepsy, alcohol dependence and opiate dependence. Since 1990 GHB has been abused in the United States for euphoric, sedative and anabolic effects. Coma and seizures have been reported following abuse of GHB, but dependence liability has received little attention. The neuropharmacology, potential therapeutic uses and acute adverse effects of GHB are reviewed, followed by a case series of eight people using GHB. Adverse effects of GHB may include prolonged abuse, seizure activity and a withdrawal syndrome. This withdrawal syndrome includes insomnia, anxiety and tremor; withdrawal symptoms resolve in 3-12 days. GHB has the potential to cause a significant incidence of abuse and adverse effects. Prolonged use of high doses may lead to a withdrawal syndrome, which resolves without sequelae. Educational efforts should address the narrow therapeutic index, possible physical dependence and dangers of combining GHB with other drugs of abuse.
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PMID:Gamma-hydroxybutyrate: an emerging drug of abuse that causes physical dependence. 937 74

We describe a 68-year-old man with a 53-month history of progressive dementia and clinical features of a progressive supranuclear palsy-like syndrome and dysautonomia. In the late stage of his illness, the patient also developed generalized myoclonic seizures. There was no family history of similar disorders. Histological examination revealed neuronal loss and gliosis with spongiosis in the cerebral cortex. In addition, more severe neuronal loss and gliosis without spongiosis were observed in the thalamus, especially in the anterior ventral and mediodorsal nuclei, and the inferior olivary nucleus. There was also obvious loss of Purkinje cells. Immunohistochemically, no protease-resistant prion protein (PrPres)-positive structures were demonstrated. However, Western blotting revealed the presence of PrPres in the cerebral cortex. This patient had a wild type of PrP genotype. We initially considered this to be a case of the thalamic form of Creutzfeldt-Jakob disease (CJD) with a long duration. However, it is noteworthy that essentially similar pathology, albeit with less severe cerebral cortical changes, has also been reported in fatal familial insomnia, a newly identified phenotypically different prion disease with a mutation in the PrP gene. On the basis of clinicopathological features, we eventually felt that this patient was more likely to have been a sporadic case of fatal insomnia (FI) of long duration. The present case appears to draw further attention to the possible relationship between CJD and FI.
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PMID:Thalamic form of Creutzfeldt-Jakob disease or fatal insomnia? Report of a sporadic case with normal prion protein genotype. 908 66

Children with asthma frequently have significant anxiety and depression that interfere with treatment outcome. Although the use of antidepressants may be helpful, in the one published study of antidepressant use in pediatric asthma, significant side effects necessitated discontinuance; these side effects were increased motor activity, impulsive behavior, insomnia, postural hypotension, premature auricular contractions, diastolic hypertension, and generalized seizure. The objective of this retrospective chart review was to examine whether antidepressants could be tolerated and administered safely to children on asthma medications. Forty pediatric inpatients (mean age 13.3 years, range 7-19) with varying levels of asthma severity (5 mild, 11 moderate, 24 severe) and an average duration of asthma treatment of 10.0 years were administered antidepressants while also taking an average of 5 medications for asthma (range 2-7). Ten of the patients had an additional comorbid medical diagnosis. There were 17 children diagnosed with a primary affective disorder; 7 with a primary anxiety disorder; and 16 with both an affective and anxiety disorder. Thirty-six children ultimately were continued on an antidepressant: 13 on desipramine, 9 on nortriptyline, 6 on imipramine, 4 on fluoxetine, 3 on bupropion, and 1 on sertraline. Significant cardiovascular side effects (tachycardia, hypertension, and postural hypotension) occurred in 4 subjects on tricyclic antidepressants (TCAs) and 1 subject on a non-TCA (fluoxetine); 3 of these subjects were able to continue treatment with an antidepressant. Two subjects were taken off antidepressants because of hypomanic symptoms (increased motor activity, mood lability, impulsive behavior, and insomnia). No medications were discontinued because of electrocardiogram changes, arrhythmias, or seizures. Doses of TCAs were comparable to those in previous studies, but the asthma medications differed. Discussion of current anti-asthmatic medications and potential for interactions with antidepressants is included.
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PMID:Cardiovascular effects of tricyclic antidepressants in childhood asthma: a case series and review. 919 41

Beginning in 1990, the Department of Psychiatry. Tripler Army Medical Center developed a formal treatment program for post-traumatic stress disorder (PTSD). Between 1990 and 1996, 632 patients, the vast majority of whom suffered from combat-related PTSD, were treated. Historically, many PTSD patients were treated with benzodiazepines, often in high dosages. The risks attendant to benzodiazepine management of PTSD, coupled with poor clinical outcome, prompted the staff to explore treatment alternatives. This paper describes the role of pharmacotherapy in the management of PTSD. The medications described in this paper have other primary uses in clinical practice (e.g., hypertension, insomnia, seizure control, depression, and anxiety). Medications were selected for use based on the putative modes of action and the degree of symptom relief. The therapeutic rationale was to decrease hyperarousal and sleep disturbance to permit the patients to engage in other psychotherapeutic efforts.
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PMID:Pharmacological management of post-traumatic stress disorder: clinical summary of a five-year retrospective study, 1990-1995. 929 Feb 98

These clinical guidelines, which have been reviewed and approved by the Board of Directors of the American Sleep Disorders Association, provide recommendations for the practice of sleep medicine in North America regarding the indications for polysomnography in the diagnosis of sleep disorders. Diagnostic categories that are considered include the following: sleep-related breathing disorders; neuromuscular disorders and sleep-related symptoms; chronic lung disease; narcolepsy; parasomnias; sleep-related epilepsy; restless legs syndrome; periodic limb movement disorder; depression with insomnia; and circadian rhythm sleep disorders. Whenever possible, conclusions are based on evidence from review of the literature. Where scientific data are absent, insufficient, or inconclusive, recommendations are based on consensus of opinion. The Standards of Practice Committee of the American Sleep Disorders Association appointed a task force to review the topic, the indications for polysomnography and related procedures. Based on the review and on consultation with specialists, the subsequent recommendations were developed by the Standards of Practice Committee and approved by the Board of Directors of the American Sleep Disorders Association. Polysomnography is routinely indicated for the diagnosis of sleep-related breathing disorders; for continuous positive airway pressure (CPAP) titration in patients with sleep-related breathing disorders; for documenting the presence of obstructive sleep apnea in patients prior to laser-assisted uvulopalatopharyngoplasty; for the assessment of treatment results in some cases; with a multiple sleep latency test in the evaluation of suspected narcolepsy; in evaluating sleep-related behaviors that are violent or otherwise potentially injurious to the patient or others; and in certain atypical or unusual parasomnias. Polysomnography may be indicated in patients with neuromuscular disorders and sleep-related symptoms; to assist in with the diagnosis of paroxysmal arousals or other sleep disruptions thought to be seizure-related; in a presumed parasomnia or sleep-related epilepsy that does not respond to conventional therapy; or when there is a strong clinical suspicion of periodic limb movement disorder. Polysomnography is not routinely indicated to diagnose chronic lung disease; in cases of typical, uncomplicated, and noninjurious parasomnias when the diagnosis is clearly delineated; for patients with epilepsy who have no specific complaints consistent with a sleep disorder; to diagnose or treat restless legs syndrome; for the diagnosis of circadian rhythm sleep disorders; or to establish a diagnosis of depression.
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PMID:Practice parameters for the indications for polysomnography and related procedures. Polysomnography Task Force, American Sleep Disorders Association Standards of Practice Committee. 930 25

Felbamate, 2-phenyl-1,3-propanediol dicarbamate, is an antiepileptic drug recently approved by the United States Food and Drug Administration. It has a novel mechanism of action whereby it may decrease excitation by inhibiting glycine binding at the NMDA receptor, and it appears to have neuroprotective properties in addition to antiepileptic ones. A number of animal models have demonstrated felbamate to have a broad range of efficacy as well as a favorable safety profile. In humans it has been potentially linked to some cases of aplastic anemia. It is effective in the treatment of partial and secondarily generalized tonic-clonic seizures as well as seizures associated with the Lennox-Gastaut syndrome, especially drop attacks. It may also be effective against atypical absence as well as other seizure types. Felbamate monotherapy is generally well tolerated, with such side effects as insomnia and anorexia occurring most commonly. Felbamate shows great promise as a useful antiepileptic drug, but its role in clinical practice awaits further investigation of recently reported cases of aplastic anemia.
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PMID:Felbamate pharmacology and use in epilepsy. 931 88

Fatal Familial Insomnia is a hereditary prion disease characterized by a mutation at codon 178 of the prion protein gene cosegregating with the methionine polymorphism at codon 129 of the mutated allele. It is characterized by disturbances of the wake-sleep cycle, dysautonomia and somatomotor manifestations (myoclonus, ataxia, dysarthria, spasticity). PET studies disclose severe thalamic and additionally cortical hypometabolism. Neuropathology shows marked neuronal loss and gliosis in the thalamus, especially the medio-dorsal and anterior-ventral nuclei, olivary hypertrophy and some spongiosis of the cerebral cortex. Detailed analysis of 14 cases from 5 unrelated families showed that patients ran either a short (9.1 +/- 1.1 months) or a prolonged (30.8 +/- 21.3 months) clinical course according to whether they were homozygote met/met or heterozygote met/val at codon 129. Moreover, homozygotes had more prominent oneiric episodes, insomnia and dysautonomia at onset, whereas heterozygotes showed ataxia and dysarthria at onset, earlier sphincter loss and epileptic Grand Mal seizures; they also displayed more extensive cortical involvement on PET and at postmortem examination. Our data suggest that the phenotype expression of Fatal Familial Insomnia is related, at least partly, to the polymorphism at codon 129 of the prion protein-gene.
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PMID:Clinical features of fatal familial insomnia: phenotypic variability in relation to a polymorphism at codon 129 of the prion protein gene. 966 7


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