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)

Flurazepam, temazepam, and triazolam are compared in terms of initial and short term efficacy, effectiveness during intermediate and long term use, withdrawal effects, and general side effects. The usefulness of temazepam is considerably restricted since the drug is slowly absorbed; peak blood concentrations are not reached until 2 to 3 hours after ingestion. Consequently, while the majority of insomniac patients complain primarily of difficulty falling asleep, temazepam is not effective for this sleep complaint. Further, the drug has an intermediate elimination half-life and induces a significant degree of morning sleepiness (hang-over). Rebound insomnia of a moderate degree occurs with some frequency following withdrawal of temazepam. Triazolam is effective initially and with short term use both for inducing and maintaining sleep. However, much of this effectiveness is lost with continued nightly use over an intermediate period (2 weeks). The drug has a rapid elimination rate; during drug administration, sleep may worsen in the final hours of the night (early morning insomnia), and following drug withdrawal, rebound insomnia is frequent, immediate, and severe. Side effects are frequent and include some morning sleepiness (before tolerance develops) and significant memory impairment and even episodes of amnesia. Triazolam may have a narrow margin of safety in that serious behavioral symptoms have been reported even with a 1-mg dose. Flurazepam is effective both for initiating and maintaining sleep with initial and short term drug administration. Further, its efficacy is maintained not only with intermediate term use but with long term drug use (4 weeks). Flurazepam is a long elimination half-life drug, and there is significant daytime sedation during short term use; with continued use this effect diminishes. Rebound insomnia has not been noted following withdrawal of flurazepam; there is a carry-over effectiveness into the first and second nights of withdrawal, and any withdrawal sleep disturbance would be expected to be infrequent, delayed in appearance, and mild in degree.
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PMID:Sleep laboratory studies of hypnotic drugs: efficacy and withdrawal effects. 613 33

Within a double-blind, comparative study on the effects of the long-half-life benzodiazepine (BDZ), quazepam, and the short-half-life BDZ, triazolam, on clinical symptomatology, sleep and anxiety of 45 patients with insomnia based on a mild to moderate generalized anxiety disorder (GAD) (ICD-9 code: 307.42-1, 300,0; ASDC-APSS-Code: A.2.a), we compared, in a first step at baseline, drug-free polysomnographic and psychometric data of 22 patients recorded in the laboratory (L-group) and 21 patients recorded by the Oxford Medilog 9000 system at home (H-group) with those of normal controls. Sleep efficiency, total sleep time, wake within total sleep period (middle insomnia) and wake before buzzer (late insomnia) were significantly deteriorated in both patient groups as compared with controls, while sleep induction time only differed significantly in home recordings. Regarding sleep architecture, stage (S)2 was reduced, S3 and S4 increased in the H-group only, while no intergroup differences were seen in S1, SREM and REM latency. Subjective sleep quality was reduced in both patient groups, but not awakening quality. Psychometric tests in the morning demonstrated for the noopsyche, only a significantly deteriorated psychomotor activity in both patient groups. In the thymopsyche, evening well-being and mood in the morning were reduced in both the L- and H-group, affectivity and morning well-being only in the H-group. The psychopharmacological part of the study was completed by 40 patients (there were 4 drop-outs in the triazolam, 1 in the quazepam group). They were treated after 1 week placebo with either 15-30 mg (median 15 mg) quazepam or 0.25-0.5 mg (median 0.25 mg) triazolam for 4 weeks, and thereafter for 2 weeks with placebo. Anxiety (rated by HAMA and SAS) improved significantly with both drugs and remained improved throughout 2 weeks post-drug placebo, with quazepam being slightly superior to triazolam. Polysomnography demonstrated a shortened sleep onset only after quazepam. Sleep efficiency improved after acute administration of both drugs, but the improvement was maintained by quazepam only (tolerance development with triazolam). Rebound insomnia was observed only in the 1st post-triazolam placebo night (significant intergroup difference based on confirmatory testing). S2 increased, S3 + S4 decreased under and after quazepam, which represents a normalization in home-recorded GAD patients. S1 decreased with both drugs, SREM only under quazepam. Subjective sleep quality behaved very similarly to objective sleep efficiency. Awakening quality improved after acute therapy with both drugs, somatic complaints only with quazepam.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Insomnia in generalized anxiety disorder: polysomnographic, psychometric and clinical investigations before, during and after therapy with a long- versus a short-half-life benzodiazepine (quazepam versus triazolam). 817 May 29

Rebound insomnia has been reported upon discontinuation of benzodiazepines. We describe the first case of a sleep polygraphically documented rebound insomnia with an unusual somatic fatigue syndrome after long-term use of clozapine in a 30-year-old schizophrenic male. The withdrawal symptoms occurred the first day after drug discontinuation and could be stopped by readministering clozapine. In our opinion, the sudden occurrence of the withdrawal symptoms cannot be explained by a dopaminergic hypersensitivity or a cholinergic rebound, but indicates an involvement of GABAergic and perhaps antiglutamatergic properties of clozapine.
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PMID:Rebound insomnia after abrupt clozapine withdrawal. 906 12

Differences in development of tolerance and occurrence of rebound insomnia have been well established between rapidly and slowly eliminated benzodiazepine hypnotics. Based on meta-analytic methodology, this study assesses whether there are such differences among the rapidly eliminated benzodiazepine and benzodiazepine-like hypnotics (brotizolam, midazolam, triazolam, zolpidem and zopiclone). All sleep laboratory studies of these drugs (n = 137) published from 1966 to 1997 were obtained, mainly through a MEDLINE search. Rigorous selection criteria resulted in the inclusion of 75 studies employing 1276 individuals (804 insomniacs and 472 healthy volunteers). Using a mixed effects regression model, reliable estimation of the effects on insomniacs of the recommended dose of each drug could be obtained. All five rapidly eliminated hypnotics showed statistically significant initial efficacy. Tolerance with intermediate and long-term use was clearly developed with triazolam and was only marginal with midazolam and zolpidem; it could not be estimated for brotizolam or zopiclone because of insufficient data. Rebound insomnia on the first withdrawal night was intense with triazolam and mild with zolpidem; data were unavailable for brotizolam and inadequate for midazolam and zopiclone. In conclusion, there are differences among the rapidly eliminated hypnotics with respect to tolerance and rebound insomnia suggesting that, in addition to short elimination half-life, other pharmacological properties are implicated in the mechanisms underlying these side-effects.
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PMID:Tolerance and rebound insomnia with rapidly eliminated hypnotics: a meta-analysis of sleep laboratory studies. 1052 72

Zaleplon is a pyrazolopyrimidine hypnotic agent which is indicated for the short term (2 to 4 weeks) management of insomnia. Zaleplon 5 and 10 mg at bedtime (usual recommended doses) significantly reduced sleep latency compared with placebo in clinical trials in nonelderly and elderly patients with insomnia. In general, sleep maintenance (sleep duration and number of awakenings) and sleep quality were not significantly different from placebo with zaleplon 5 and 10 mg/night. Zaleplon 20 mg/night significantly improved sleep latency and duration in nonelderly patients, but effects on number of awakenings were inconsistent and sleep quality generally did not improve. The relative hypnotic efficacy of zaleplon compared with that of triazolam and zolpidem is not yet clearly established. Tolerance to the hypnotic effects of zaleplon generally did not occur during 5 weeks' treatment, or during long term treatment (6 or 12 months) according to a small number of studies presented as abstracts. Zaleplon was well tolerated in clinical trials. The most common event was headache but the incidence was similar to that observed with placebo. Zaleplon 5 and 10 mg did not impair psychomotor function or memory even immediately after the dose in studies in volunteers or patients with insomnia. Zaleplon 20 mg, however, impaired psychomotor function and memory immediately after the dose but next-day effects were not observed. The psychomotor profile of zaleplon appears to be better than that of comparator agents. Rebound insomnia was not observed after sudden discontinuation of up to 12 months' treatment with zaleplon 5 and 10 mg/night and up to 4 weeks' treatment with zaleplon 20 mg/night. In addition, the potential for withdrawal syndrome with zaleplon appears to be low according to limited data. In conclusion, zaleplon 5, 10 and 20 mg administered at bedtime, or later if patients have difficulty sleeping, is an effective and well tolerated hypnotic agent. There was no evidence of next-day residual effects with the 5 and 10 mg dosages, and the incidence of withdrawal effects with zaleplon 5, 10 and 20 mg did not differ significantly to that observed with placebo. In addition, tolerance to the effects of zaleplon is unlikely to develop when administered for the recommended treatment period. The comparative efficacy and tolerability of zaleplon with other short acting nonbenzodiazepine hypnotics is difficult to establish. However, on the basis of current efficacy evidence and the lower incidence of residual effects with zaleplon 5 and 10 mg relative to comparator agents, this drug represents a useful option in the management of patients with insomnia who have difficulties initiating sleep.
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PMID:Zaleplon: a review of its use in the treatment of insomnia. 1098 40

Benzodiazepine hypnotics, the mainstay of pharmacological treatment for insomnia, have been associated with altered sleep architecture, psychomotor and memory impairment, rebound insomnia, withdrawal effects, tolerance, dependence, abuse potential and respiratory depression. Non-benzodiazepines, such as zolpidem, zopiclone and zaleplon, demonstrate hypnotic efficacy similar to that of benzodiazepines along with excellent safety profiles. Non-benzodiazepines generally cause less disruption of normal sleep architecture than benzodiazepines. Psychomotor and memory impairment may be less problematic with non-benzodiazepines, especially when compared to longer-acting benzodiazepines. Rebound insomnia and withdrawal symptoms occur infrequently upon discontinuation of non-benzodiazepines and may be less common and milder than those seen upon discontinuation of some benzodiazepines. For the long-term treatment of insomnia, which is generally not recommended, zolpidem and zopiclone are particularly good options because they do not develop tolerance rapidly and have a low abuse potential. Limited data indicate that zaleplon has low tolerance and abuse potential, although further experience is needed to determine its long-term efficacy and safety profile. Since non-benzodiazepines produce minimal respiratory depression, they may be safer than benzodiazepines in patients with respiratory disorders. The choice of which hypnotic to use should be based on the patient's primary sleep complaint, health history, adverse effects and cost.
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PMID:Non-benzodiazepines for the treatment of insomnia. 1253 Oct 36

Melatonin, secreted nocturnally by the pineal gland, is an endogenous sleep regulator. Impaired melatonin production and complaints on poor quality of sleep are common among the elderly. Non-restorative sleep (perceived poor quality of sleep) and subsequently poor daytime functioning are increasingly recognized as a leading syndrome in the diagnostic and therapeutic process of insomnia complaints. The effects of 3-weeks prolonged-release melatonin 2 mg (PR-melatonin) versus placebo treatment were assessed in a multi-center randomized placebo-controlled study in 170 primary insomnia outpatients aged > or =55 years. Improvements in quality of sleep (QOS) the night before and morning alertness (BFW) were assessed using the Leeds Sleep Evaluation Questionnaire and changes in sleep quality (QON) reported on five categorical unit scales. Rebound insomnia and withdrawal effects following discontinuation were also evaluated. PR-melatonin significantly improved QOS (-22.5 versus -16.5 mm, P = 0.047), QON (0.89 versus 0.46 units; P = 0.003) and BFW (-15.7 versus -6.8 mm; P = 0.002) compared with placebo. The improvements in QOS and BFW were strongly correlated (Rval = 0.77, P < 0.001) suggesting a beneficial treatment effect on the restorative value of sleep. These results were confirmed in a subgroup of patients with a greater symptom severity. There was no evidence of rebound insomnia or withdrawal effects following treatment discontinuation. The incidence of adverse events was low and most side-effects were judged to be of minor severity. PR-melatonin is the first drug shown to significantly improve quality of sleep and morning alertness in primary insomnia patients aged 55 years and older-suggesting more restorative sleep, and without withdrawal symptoms upon discontinuation.
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PMID:Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. 1803 82

Eszopiclone is the S-isomer of racemic zopiclone, a cyclopyrrolone with sedative-hypnotic activity that has been available in Europe, Canada, and Latin America since 1987. Eszopiclone acts by binding to the GABA(A) receptor. In contrast to the benzodiazepine (BZD) hypnotics, eszopiclone has more selectivity for certain subunits of the GABA(A) receptor. Oral eszopiclone is rapidly absorbed and extensively distributed to body tissues including the brain. Peak plasma concentrations are attained 1.0-1.6 hours after a 3 mg dose, while the mean elimination half-life is 6 hours. The half-life increases with age to about 9.0 hours in patients 65 years or older. Eszopiclone's pharmacokinetic (PK) profile is not substantially modified in patients suffering from renal failure or mild-to-moderate hepatic impairment, although patients with severe hepatic insufficiency should have a reduced dose. The subjective perception of improved sleep following eszopiclone 2 or 3 mg treatment has been demonstrated in randomized, double-blind, placebo-controlled studies of up to 6 months' duration. In these studies the drug significantly reduced sleep onset latency (SOL), the number of awakenings, and wake time after sleep onset (WASO) whereas total sleep time (TST) and quality of sleep were increased in non-elderly and elderly subjects. Sleep laboratory studies of the effects of eszopiclone have confirmed the drug's clinical efficacy in subjects with chronic primary insomnia. Eszopiclone, unlike BZD hypnotics, does not significantly alter values corresponding to slow wave sleep (SWS or stages 3 and 4) and rapid eye movement (REM) sleep. Rebound insomnia following withdrawal of eszopiclone has been examined in only one study. Discontinuation of the active treatment with 2 mg was followed by rebound insomnia in non-elderly subjects. Three-mg doses of eszopiclone administered for a period of up to 12 months was associated with a sustained beneficial effect on sleep induction and maintenance, with no occurrence of tolerance. The most common side-effects were unpleasant or bitter taste, headache, dyspepsia, pain, diarrhea, dry mouth, upper respiratory infection, urinary tract infection, dizziness, and accidental injury. New adverse events (withdrawal symptoms) including anxiety, abnormal dreams, hyperesthesia, nausea, and upset stomach were recorded in one study on the days following eszopiclone 2 or 3 mg discontinuation. Although dependence and abuse potential have not been formally assessed, unpublished data show that eszopiclone at doses of 6 and 12 mg produces euphoria effects similar to those of diazepam 20 mg in BZD drug addicts. In conclusion, available evidence tends to indicate that eszopiclone is effective and safe for the treatment of chronic primary insomnia in non-elderly and elderly subjects. Tolerance did not occur during active drug administration for a 12-month period. Thus eszopiclone can be efficacious not only during short- and intermediate-term administration but also in patients requiring prolonged regular drug usage.
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PMID:Eszopiclone: its use in the treatment of insomnia. 1930 May 73

Rebound insomnia, worsened sleep when discontinuing use of a hypnotic, is reported in some short-term studies. No study has prospectively assessed, using patient reports or nocturnal polysomnography (NPSG), the likelihood of rebound insomnia with chronic hypnotic use. The objectives of this study was to assess in primary insomniacs the likelihood of experiencing rebound insomnia and a withdrawal syndrome on repeated placebo substitutions over 12 months of nightly zolpidem use. A group of 33 primary insomniacs, without psychiatric disorders or drug and alcohol abuse, 32-65 years old, 15 men and 18 women, were randomized to take zolpidem 10 mg (n = 17) or placebo (n = 16) nightly for 12 months. In probes during months 1, 4, and 12, placebo was substituted for 7 consecutive nights in both the zolpidem and placebo groups. NPSGs were collected and Tyrer Bezodiazepine Withdrawal Symptom Questionnaires were completed on the first two discontinuation nights. Rebound insomnia was not observed on the first two and the seventh discontinuation nights and its likelihood did not increase over the 12 months of nightly zolpidem use. Some individuals did show rebound insomnia, approximately 30-40% of participants, but the percentage of 'rebounders' did not differ between the placebo and zolpidem groups and did not increase across 12 months. No clinically significant withdrawal symptoms on the Tyrer were observed on the discontinuation nights over the 12 months of nightly use. Chronic nightly hypnotic use at therapeutic doses by primary insomniacs does not lead to rebound insomnia or withdrawal symptoms.
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PMID:Twelve months of nightly zolpidem does not lead to rebound insomnia or withdrawal symptoms: a prospective placebo-controlled study. 2200 89

Surveillance studies are useful to evaluate how a new medicinal product performs in everyday treatment and how the patient who takes it feels and functions, thereby determining the benefit/risk ratio of the drug under real-life conditions. Prolonged-release melatonin (PRM; Circadin) was approved in Europe for the management of primary insomnia patients age 55 years or older suffering from poor quality of sleep. With traditional hypnotics (e.g. benzodiazepine-receptor agonists), there are concerns about rebound insomnia and/or withdrawal symptoms. We report data from a postmarketing surveillance study in Germany on the effects of 3 weeks of treatment with PRM on sleep in patients with insomnia during treatment and at early (1-2 days) and late (around 2 weeks) withdrawal. In total, 653 patients (597 evaluable) were recruited at 204 sites (mean age 62.7 years, 68% previously treated with hypnotics, 65% women). With PRM treatment, the mean sleep quality (on a scale of 1-5 on which 1 is very good and 5 is very bad) improved from 4.2 to 2.6 and morning alertness improved from 4.0 to 2.5. The improvements persisted over the post-treatment observation period. Rebound insomnia, defined as a one-point deterioration in sleep quality below baseline values, was found in 3.2% (early withdrawal) and 2.0% (late withdrawal). Most of the patients (77%) who used traditional hypnotics before PRM treatment had stopped using them and only 5.6% of naive patients started such drugs after PRM discontinuation. PRM was well tolerated during treatment and the most frequently reported adverse events were nausea (10 patients, 1.5%), dizziness, restlessness and headache (five patients each, <1%). There were no serious adverse events and no adverse events were reported after discontinuation. The persisting treatment effect and very low rebound rate suggest a beneficial role of sleep-wake cycle stabilization with PRM in the treatment of insomnia.
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PMID:Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin. 2505 34


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