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

Although over 20 years of clinical experience with benzodiazepine hypnotics have demonstrated their relative safety, flurazepam, temazepam, triazolam, and quazepam do not have identical safety profiles. Dose-related central nervous system (CNS) depression such as daytime sedation and psychomotor impairment may be expected because they are an extension of the therapeutic action of these agents. Therefore, drug dose is an important factor in determining the expected frequency and severity of these side effects. Also, it is important for a clinician not to assume that these unwanted CNS effects relate only to the length of a drug's half-life. Half-life does appear to be an important determinant of the presence or absence of rebound insomnia.
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PMID:A review of the safety profiles of benzodiazepine hypnotics. 168 Jan 24

The abuse liability of a drug is a positive, interactive function of the reinforcing and adverse effects of the drug. The relative abuse liability of the hypnotic benzodiazepine, triazolam, has been controversial. This paper reviews animal and human studies bearing on its relative abuse liability, including data on pharmacological profile, reinforcing effects, liking, speed of onset, discriminative stimulus effects, subjective effects, physiological dependence, rebound and early morning insomnia, drug produced anxiety, lethality in overdose, psychomotor impairment, interactions with ethanol, anterograde amnesia, impaired awareness of drug effect, and other psychiatric and behavioral disturbances. It is concluded that the abuse liability of triazolam is less than that of the intermediate duration barbiturates such as pentobarbital. Although there are considerable data indicating similarities of triazolam to other benzodiazepines, there is also substantial speculation among clinical investigators and some limited data suggesting that the abuse liability of triazolam is greater than that of a variety of other benzodiazepines, and virtually no credible data or speculation that it is less. Further research will be necessary to clarify definitively the abuse liability of triazolam relative to other benzodiazepines.
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PMID:Relative abuse liability of triazolam: experimental assessment in animals and humans. 285 78

Benzodiazepine hypnotics are used for short periods in low doses in healthy people when stressed and in patients with insomnia. This study examined psychomotor impairment in healthy young males and females after 1 and 7 nights of flunitrazepam (1 mg), nitrazepam (2.5 mg) and temazepam (10 mg). There were substantial inter-individual variations. Results showed that no drug significantly affected psychomotor performance at these doses after single or repeated administration. The number and severity of side-effects were significantly greater after the first night with temazepam and 7 nights with nitrazepam, although this may reflect a statistical artefact rather than a significant clinical finding. The difficulties in performing adequately controlled psychopharmacological studies at low doses are highlighted. Given the large intra- and inter-subject variances, small drug effects would necessitate large sample sizes (21 to 600 subjects at the 95% level of chance of detection) depending on the variable. The study suggests there is minimal impairment with low dose hypnotic drugs and a need to individualize treatment.
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PMID:The psychomotor effects of single and repeated doses of hypnotic benzodiazepines. 369 71

Flunitrazepam is a benzodiazepine derivative whose hypnotic effect predominates over the sedative, anxiolytic, muscle-relaxing and anticonvulsant effects characteristic of benzodiazepines. Thus, it is used as a night-time hypnotic and in anaesthesiology: due to the pronounced hypnotic effect it is not appropriate as a daytime sedative. As a hypnotic for insomnia its effect is usually characterised by a very fast onset of action and quiet sleep without interruptions. On the morning after a hypnotic dose some residual psychomotor impairment does occur, which is comparable to that with usual doses of nitrazepam or flurazepam, but clinically apparent 'hangover' occurs infrequently. There is no pronounced cumulative effect with chronic use. In anaesthesiology it has proven to be useful as a hypnotic on the night before operation, as an oral, intramuscular or intravenous premedication, in induction and as a supplement to other anaesthetics. Its sedative and amnesic properties can also be beneficial in intensive care patients. Much of the usefulness of flunitrazepam in anaesthesia relates to its synergistic effect with other anaesthetics, to its effective amnesic action and its acceptable effects on circulation and respiration. Possible drawbacks include a somewhat unusual course of induction (when used for this purpose) and an often prolonged recovery. Although the safe dosage range is wide with flunitrazepam, its effective application both as a hypnotic for insomnia and in anaesthesiology is dependent upon use of the optimal dosage, and adequate knowledge of its pharmacokinetic properties.
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PMID:Flunitrazepam: a review of its pharmacological properties and therapeutic use. 610 5

A multicentre, parallel group hospital study was carried out in 190 subjects with insomnia to compare the efficacy, incidence of hangover and the side-effects of loprazolam and nitrazepam. Following 2 nights single-blind phase on placebo, loprazolam (1.0 mg), nitrazepam (5.0 mg) or placebo was administered double-blind for 7 consecutive nights. Visual analogue scales and questions were used to rate efficacy. There was no statistically significant difference between loprazolam and nitrazepam for 'ease of getting to sleep', 'restfulness of sleep' and 'depth of sleep'. Like nitrazepam, loprazolam diminished the number of periods of wakefulness and made it 'easier to get to sleep again'. Subjective evaluation showed that hangover was not a feature of loprazolam. It did not affect morning alertness and patients thought they had improved balance and co-ordination while on this drug. These findings are in keeping with the evidence of other workers who have shown only minimal psychomotor impairment, if any, with loprazolam (1.0 mg). There was no statistically significant difference between treatments with respect to frequency or incidence of side-effects.
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PMID:A multicentre hospital study to compare the hypnotic efficacy of loprazolam and nitrazepam. 614 85

The main actions of benzodiazepines (hypnotic, anxiolytic, anticonvulsant, myorelaxant and amnesic) confer a therapeutic value in a wide range of conditions. Rational use requires consideration of the large differences in potency and elimination rates between different benzodiazepines, as well as the requirements of individual patients. As hypnotics, benzodiazepines are mainly indicated for transient or short term insomnia, for which prescriptions should if possible be limited to a few days, occasional or intermittent use, or courses not exceeding 2 weeks. Temazepam, loprazolam and lormetazepam, which have a medium duration of action are suitable. Diazepam is also effective in single or intermittent dosage. Potent, short-acting benzodiazepines such as triazolam appear to carry greater risks of adverse effects. As anxiolytics, benzodiazepines should generally be used in conjunction with other measures (psychological treatments, antidepressants, other drugs) although such measures have a slower onset of action. Indications for benzodiazepines include acute stress reactions, episodic anxiety, fluctuations in generalised anxiety, and as initial treatment for severe panic and agoraphobia. Diazepam is usually the drug of choice, given in single doses, very short (1 to 7 days) or short (2 to 4 weeks) courses, and only rarely for longer term treatment. Alprazolam has been widely used, particularly in the US, but is not recommended in the UK, especially for long term use. Benzodiazepines also have uses in epilepsy (diazepam, clonazepam, clobazam), anaesthesia (midazolam), some motor disorders and occasionally in acute psychoses. The major clinical advantages of benzodiazepines are high efficacy, rapid onset of action and low toxicity. Adverse effects include psychomotor impairment, especially in the elderly, and occasionally paradoxical excitement. With long term use, tolerance, dependence and withdrawal effects can become major disadvantages. Unwanted effects can largely be prevented by keeping dosages minimal and courses short (ideally 4 weeks maximum), and by careful patient selection. Long term prescription is occasionally required for certain patients.
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PMID:Guidelines for the rational use of benzodiazepines. When and what to use. 752 93

The benzodiazepines are still extensively used in psychiatry, neurology and medicine in general. Anxiety disorder and severe insomnia are important syndromal indications, but these drugs are widely prescribed at the symptomatic level, resulting in potential overuse. The official data sheets recommend short durations of usage and conservative dosage. Although short-term efficacy is established, long-term efficacy remains controversial, as relevant data are scanty and relapse, rebound and dependence on withdrawal not clearly distinguished. The risks of the benzodiazepines are well-documented and comprise psychological and physical effects. Among the former are subjective sedation, paradoxical release of anxiety and/or hostility, psychomotor impairment, memory disruption, and risks of accidents. Physical effects include vertigo, dysarthria, ataxia with falls, especially in the elderly. Dependence can supervene on long-term use, occasionally with dose escalation. The benzodiazepines are now recognised as major drugs of abuse and addiction. Other drug and non-drug therapies are available and have a superior risk benefit ratio in long-term use. It is concluded that benzodiazepines should be reserved for short-term use--up to 4 weeks--and in conservative dosage.
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PMID:Limitations on the use of benzodiazepines in anxiety and insomnia: are they justified? 1062 86

Insomnia is problematic for many individuals, causing them to seek treatment. There is a long history of therapies aimed at restoring normal sleep patterns, each having its advantages and disadvantages. This review traces the history of insomnia drug therapies from chloral hydrate and the barbiturates through the benzodiazepines and explores the newest selective benzodiazepine receptor agonists, including zolpidem and zaleplon. The mechanisms of action of the benzodiazepine receptor agonists are compared and contrasted. A pharmacokinetic comparison is presented showing the importance that parameters such as dose, onset of action, lipophilicity, metabolites, half-life, and receptor-binding affinity have on clinical effects. The possible adverse effects of sleep aids are discussed, including residual sedation and psychomotor impairment, daytime anxiety, anterograde amnesia and cognitive impairment, rebound insomnia, and drug tolerance and dependence. Effects on sleep efficiency and staging are also discussed. Recommendations for the primary care physician on the selection of hypnotics are also provided. Benzodiazepine receptor agonists are often appropriate agents in the treatment of insomnia; however, individual drug and patient considerations are important in matching the most appropriate agent to the individual patient. Zolpidem and zaleplon, newer selective benzodiazepine receptor agonists, offer additional treatment options.
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PMID:Nonselective and selective benzodiazepine receptor agonists--where are we today? 1075 7

This paper reviews the use of sleep-promoting medications in nursing home residents with reference to risks versus benefits. Up to two-thirds of elderly people living in institutions experience sleep disturbance. The aetiology of sleep disturbance includes poor sleep hygiene, medical and psychiatric disorders, sleep apnoea, periodic limb movements and restless leg syndrome. One key factor in the development of sleep disturbance in the nursing home is the environment, particularly with respect to high levels of night-time noise and light, low levels of daytime light, and care routines that do not promote sleep. Clinical assessment should include a comprehensive medical, psychiatric and sleep history including a review of prescribed medications. Nonpharmacological interventions for insomnia are underutilised in many clinical settings despite evidence that they are often highly effective. International studies suggest that 50-80% of nursing home residents have at least one prescription for psychotropic medication. Utilisation rates vary dramatically from country to country and from institution to institution. The most commonly prescribed medications for sleep are benzodiazepines and nonbenzodiazepine hypnotics (Z-drugs). The vast majority of studies of these medications are short-term, i.e. < or =2 weeks, although some longer extension trials have recently been carried out. Clinicians are advised to avoid long-acting benzodiazepines and to use hypnotics for as brief a period as possible, in most cases not exceeding 2-3 weeks of treatment. Patients receiving benzodiazepines are at increased risk of daytime sedation, falls, and cognitive and psychomotor impairment. Zaleplon, zolpidem, zopiclone and eszopiclone may have some advantages over the benzodiazepines, particularly with respect to the development of tolerance and dependence. Ramelteon, a novel agent with high selectivity for melatonin receptors, has recently been approved in the US. Use of the antidepressant trazodone for sleep in nondepressed patients is somewhat controversial. Atypical antipsychotics should not be used to treat insomnia unless there is also evidence of severe behavioural symptoms or psychosis.
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PMID:Use of sleep-promoting medications in nursing home residents : risks versus benefits. 1673 87

A randomized, controlled, crossover clinical study compared 14-night treatment with 15 mg temazepam, 50 mg diphenhydramine, and placebo in elderly individuals with insomnia (mean age, 73.9 years; range, 70-89 years). Primary outcome measures were subjective assessments of sleep recorded on sleep diaries. Secondary measures were the morning-after psychomotor impairment, using the digit symbol substitution task and the manual tracking task, and the morning-after memory impairment, using a free-recall procedure. Results showed sleep improvements with 15 mg temazepam compared with placebo-sleep quality (mean score, 3.3 +/- 0.9 vs 2.9 +/- 0.8; P = 0.03), total sleep time (6.9 +/- 1.0 hours vs 6.3 +/-1.3 hours; P = 0.02), number of awakenings (1.5 +/- 1.3 vs 2.0 +/- 1.2; P < 0.001), and sleep-onset latency (25 +/- 22 minutes vs 37 +/- 25 minutes; P = 0.03). Improvements were seen with diphenhydramine treatment compared with placebo on the number of awakenings only (mean, 1.7 +/- 1.1 vs 2.0 +/- 1.2; P < 0.05). Numbers of adverse events reported were similar after all treatments, although there was 1 fall during temazepam treatment. Findings indicate that temazepam is more effective than diphenhydramine when compared with placebo at the doses tested, although this advantage is mitigated by the risk of falls associated with temazepam use. The choice of agent to use in the elderly must consider these relative benefits and risks.
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PMID:Effects of 2-week treatment with temazepam and diphenhydramine in elderly insomniacs: a randomized, placebo-controlled trial. 1834 28


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