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)

In summary, it is proposed that the more frequent or severe side effects associated with the newer triazolo-benzodiazepines are related to an interaction of several factors, including rapid elimination, high receptor-binding affinity, and unique chemical properties. Among benzodiazepine hypnotics, triazolam has a unique side effect profile for CNS adverse reactions in regard to type, frequency, and severity. All of the three factors mentioned contribute to this side effect profile: rapid elimination (the shortest half-life among benzodiazepine anxiolytics and hypnotics); high receptor-binding affinity (the highest among benzodiazepine anxiolytics and hypnotics); and unique chemical properties as a triazolo-benzodiazepine. Given these three factors, the drug's side effects can be understood as follows: Hyperexcitability states (daytime anxiety during drug administration and rebound insomnia following withdrawal) are related primarily to its rapid elimination and secondarily to the other two factors, whereas cognitive impairments (amnesia, confusion, and psychiatric symptoms) are related to the high binding affinity and unique chemical properties as well as to its rapid elimination. In contrast, benzodiazepines that are slowly eliminated and have only relatively moderate receptor-binding affinity (flurazepam) are unlikely to produce daytime anxiety and rebound insomnia and CNS adverse reactions such as cognitive impairment. The most common side effect, daytime sedation, is easily recognized and can be managed by dose reduction and/or intermittent use. This safety profile combined with the drug's high degree of efficacy both initially and with continued use provides a high benefit-risk ratio in using the drug in the adjunctive pharmacologic treatment of insomnia. Similarly, temazepam, which has relatively weak receptor-binding affinity produces very few CNS adverse reactions. Furthermore, temazepam (15 mg) is more efficacious than triazolam (0.25 mg). However, temazepam is not as effective as flurazepam, because it is slowly absorbed and therefore has limited efficacy for sleep induction. On the other hand, triazolam's safety profile of frequent and severe adverse reactions combined with the lack of efficacy for the current dose of 0.25 mg limits the drug's usefulness. In fact, the 0.25-mg dose has such a poor benefit-to-risk ratio that there is a real question as to whether the drug should remain on the market.(ABSTRACT TRUNCATED AT 400 WORDS)
Hosp Pract (Off Ed) 1990 Sep
PMID:Benzodiazepine hypnotics and insomnia. 197 24

Progressive muscle relaxation is a rational therapeutic alternative in such common functional syndromes as tension headache, migraine, and insomnia. Evidence of its efficacy and guidelines in clinical application are offered.
Hosp Pract (Off Ed) 1983 Jul
PMID:Clinical applications of relaxation training. 640 76

To provide an in vitro system that allows inducible or conditional overexpression of human prion protein (PrP), we have established a tetracycline (Tc)-regulated system in murine 3T3 L1 fibroblast cells. A replacement-type gene targeting vector cassette was constructed to express the human fatal familial insomnia (FFI) prion protein gene (PRNP) under control of a Tc-responsive element. Following stable integration of the vector into 3T3 Tet-Off cells, we have isolated and characterised six 3T3 L1 pTet-Off FFI clones. These clones were analysed by PCR and their expression level was determined by Western blot using species specific monoclonal antibodies (anti-mouse and human 3B5, 4F2, 12F10, 11C6, 8G8, and 14D3; anti-mouse l3). Addition of the antibiotic Tc to the culture medium turned off expression of human PrP. This supression was repeatedly reversible. However, no significant transcriptional leakiness of repressed PminCMV promoter was observed. In the absence of Tc, expression of human PrP was induced 10- to 20-fold as estimated from densitometric analyses. PrP was analysed by Proteinase K (PK) digestions and found to be PK sensitive. Subcellular fractionation revealed that PrP was located mainly in the cytoplasmic membrane fraction. Furthermore, we partially purified PrP by PrP-specific copper-binding. After immobilised metal affinity chromatography, majority of PrP showed a molecular weight consistent with non-glycosylated PrP. These clones offer a new tool to facilitate the investigation of PrP interaction with potential cellular ligands and PrP ex vivo propagation.
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PMID:Tetracycline-regulated highly inducible expression of the human prion protein in murine 3T3 cells. 1559 55

The popularity of antidepressants in the treatment of insomnia is not supported by a large amount of convincing data, but rather by opinions and beliefs of the prescribing physicians on the advantages of these agents compared with drugs acting on the benzodiazepine receptor or other drugs used for the treatment of insomnia. The existing data do not allow for clear-cut, evidence-based recommendations concerning the use of antidepressants in insomnia. Our conclusions result from a few short-term studies on single agents, clinical experience and inferences from knowledge on the effect of antidepressants in other indications. At present, prescribing antidepressants for short-term treatment of insomnia can be useful if there is some amount of concomitant depressive symptomology or a history of depression, raising the impression that the present insomnia may be a prodromal sign for a new depressive episode. In all other cases, benzodiazepine receptor agonists, especially the nonbenzodiazepines among them (the so-called 'z drugs') should be the drugs of choice. For long-term treatment, antidepressants are among the pharmacological options, in addition to other groups of psychotropics. Off-label use of antidepressants may be considered for chronic insomnia if there is a concomitant depressive symptomalogy (which is not so pronounced that an antidepressant treatment with adequate higher doses would be required) and if there is no specific indication for one of the other groups of psychotropics (e.g. dementia-related nocturnal agitation, in which case an antipsychotic would be preferred, or circadian problems, in which case melatonin or a melatonin agonist would be favoured). If antidepressants are used to treat insomnia, sedating ones should be preferred over activating agents such as serotonin reuptake inhibitors. In general, drugs lacking strong cholinergic activity should be preferred. Drugs blocking serotonin 5-HT2A or 5-HT2C receptors should be preferred over those whose sedative property is caused by histamine receptor blockade only. The dose should be as low as possible (e.g. as an initial dose: doxepin 25 mg, mirtazapine 15 mg, trazodone 50 mg, trimipramine 25 mg). Regarding the lack of substantial data allowing for evidence-based recommendations, we are facing a clear need for well designed, long-term, comparative studies to further define the role of antidepressants versus other agents in the management of insomnia.
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PMID:Antidepressants for the treatment of insomnia : a suitable approach? 1901 70

Atypical antipsychotics (AAP) have become some of the most commonly prescribed medications in primary and specialist care settings. Off-label prescribing accounts for much of the expanded use of AAPs. This has become common in the elderly. Marketing by pharmaceutical companies appears to have contributed to the off-label use of AAPs, in situations where their safety and efficacy is far from established. Although evidence provides varying degrees of support for their use for behavioural and psychological symptoms of dementia, augmentation of antidepressants in depression, anxiety, insomnia and in the management of psychosis in Parkinson's Disease, there are a number of potential problems with their expanded use in the elderly. These include weight gain, type two diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. It is recommended that whenever AAPs are used off-label, a review date is identified, informed consent is obtained and treatment and side-effects are closely monitored.
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PMID:Indications of atypical antipsychotics in the elderly. 2535 48

Off-label prescribing of psychiatric drugs is common, despite lacking strong scientific evidence of efficacy and potentially increasing risk for adverse events. The goal of this study was to characterize prevalence of off-label prescriptions of psychiatric drugs and examine patient and clinician predictors of off-label use. This manuscript presents a retrospective, cross-sectional study using data from the 2012 and 2013 National Ambulatory Medical Care Surveys (NAMCS). The study examined all adult outpatient visits to psychiatric practices for chronic care management with a single listed visit diagnosis in which at least one psychiatric drug was prescribed. The main outcome measure was off-label prescribing of at least one psychiatric drug, defined as prescription for a condition for which it has not been approved for use by the FDA. Among our sample representative of 1.85 billion outpatient visits, 18.5 million (1.3%) visits were to psychiatrists for chronic care management in which at least one psychiatric drug was prescribed. Overall, the rate of off-label use was 12.9% (95% CI: 12.2-15.7). The most common off-label uses were for manic-depressive psychosis treated with citalopram and primary insomnia treated with trazodone. Several patient and clinician characteristics were positively associated with off-label prescribing, including seeing a psychiatrist (OR: 1.06, 95% CI, 1.01-1.12; p = 0.03) instead of another type of clinician, the office visit taking place in the Western region of the country (OR: 1.09, 95% CI, 1.01-1.17; p = 0.02), and the patient having 3 or more chronic conditions (OR: 1.12, 95% CI, 1.02-1.14; p = 0.003). In contrast, having Medicare coverage (OR: 0.93, 95% CI, 0.84-0.97; p = 0.04) and receiving payment assistance from a medical charity (OR: 0.91, 95% CI, 0.88-0.96; p = 0.03) instead of private insurance were negatively associated with off-label prescribing. These results suggest that certain classes of psychiatric medications are being commonly prescribed to treat conditions for which they have not been determined by the FDA to be clinically efficacious and/or safe.
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PMID:Patterns and predictors of off-label prescription of psychiatric drugs. 3002 73