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

Many patients with insomnia describe their sleep problems as an inability to remain asleep throughout the night, resulting in next-day fatigue that may adversely affect daytime functioning. To be most effective, insomnia treatment should be tailored to resolving underlying causes of the condition and managing specific sleep complaints. Therefore, hypnotic therapy administered prior to bedtime, as is currently recommended for most compounds, is not appropriate for all insomnia patients. Ideally, behavioral interventions should be combined with a rapid-acting agent that can be administered at virtually any time during the night without producing residual effects the following day. Zaleplon, a new non-benzodiazepine sleep medication, provides the clinician with an effective and safe pharmacotherapeutic option for insomnia management. Its rapid rates of absorption and elimination allow for treatment of symptoms when they occur, either at bedtime or later at night, without incurring significant risk for the development of next-day impairment of psychomotor and cognitive functioning.
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PMID:Individualizing therapy for early, middle-of-the-night and late-night insomnia. 1121 29

Sleep difficulties affect about one-third of American adults, yet these symptoms are not often addressed by patients and their physicians. Unresolved insomnia that impairs daytime function may be associated with significant psychiatric morbidity, predominantly major depression. Clinicians who are aware that these disorders frequently co-exist will be able to facilitate prompt diagnosis and initiate appropriate pharmacotherapeutic intervention. Antidepressant therapies may interfere with sleep quality; therefore, the management of insomnia in depressed patients should be addressed separately. Traditionally, benzodiazepines have been prescribed to treat sleep disturbances, but certain drugs in this class have limited benefits due to residual sedative effects that impair cognitive function, memory and general daytime performance. Zaleplon, a new, quick-acting, non-benzodiazepine sleep medication, may be clinically advantageous in promoting sleep without residual impairment.
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PMID:The relationship between psychiatric diseases and insomnia. 1121 30

Zaleplon is a non-benzodiazepine sleep medication that shows efficacy as a sleep inducer comparable to that of other hypnotics but with significantly fewer residual effects. In addition, evaluations of psychomotor or memory function at zaleplon peak plasma levels show much less impairment than noted with other hypnotics, suggesting an improved benefit-to-risk profile for zaleplon compared with older available agents. Thus, zaleplon can be used to treat symptoms of insomnia when they occur without the concern of next-day psychomotor or memory impairment, whether administered at bedtime or later during the night. Such an approach permits physicians to reformulate their strategies for safe and effective management of sleeplessness.
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PMID:Efficacy and safety of zaleplon at peak plasma levels. 1121 31

The challenge in developing hypnotic agents for the treatment of insomnia is to balance the sedative effect needed at bedtime with the residual sedation on awakening. Zaleplon is a novel pyrazolopyrimidine hypnotic agent that acts as a selective agonist to the brain omega(1) receptor situated on the alpha(1) subunit of the GABA(A) receptor complex. Zaleplon was proven to be an effective hypnotic drug as it consistently and significantly reduced latency to persistent sleep in insomniac patients for doses of 10 mg and above in polysomnography studies. The pharmacodynamic profile of zaleplon on psychomotor performance, actual driving and cognitive function, including memory, was assessed in several randomized, double-blind, placebo-controlled studies in healthy young subjects as well as insomniac patients by using various positive controls (zolpidem, zopiclone, triazolam and flurazepam). The recommended hypnotic dose of zaleplon in young adults (10 mg) produced minimal or no impairment of psychomotor and memory performance even when administered during the night as little as 1 h before waking. No impairment of actual driving was observed when zaleplon 10 mg was administered either at bedtime or in the middle of the night as little as 4 h before waking. Zaleplon 20 mg, twice the recommended dose, generally produced significant impairment of performance and cognitive functions when these functions were measured at the time of peak plasma concentration, i.e. 1 h after dose administration, and no impairment of driving abilities was observed 4 h after a middle-of-the-night administration. In contrast, consistent detrimental residual effects on various aspects of psychomotor and cognitive functions were observed with the therapeutic doses of the various commonly prescribed hypnotic agents used as comparators, e.g. zolpidem 10 mg up to 5 h after dose administration, zopiclone 7.5 mg up to 10 h after, flurazepam 30 mg up to 14 h after and triazolam 0.25 mg up to 6 h after. Also, zolpidem 10 mg and zopiclone 7.5 mg were also shown to significantly impair driving ability the next morning when this was measured 4 h and up to 10 h after dose administration, respectively. The present review shows that zaleplon 10 mg has little or no residual effect when administered in the middle of the night, as late as 1 h before waking, and is devoid of impairment of driving abilities as assessed by actual driving 4 h after dose administration. The lack of clinically significant or minimally statistically significant residual effects of zaleplon even at its peak concentration may be explained by its unique pharmacokinetic (rapid elimination half-life) and pharmacodynamic (low affinity, and specific binding profile to various subunits of the GABA(A)receptor) profiles. These properties allow zaleplon to be used for treatment of symptoms only when they occur, either at bedtime or later in the night, without incurring significant risk of developing next-day impairment of psychomotor and cognitive functioning. Copyright 2001 John Wiley & Sons, Ltd.
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PMID:Pharmacodynamic profile of Zaleplon, a new non-benzodiazepine hypnotic agent. 1240 58

The effects of two nights of treatment with the short-acting benzodiazepine receptor agonist zaleplon, triazolam, or placebo was assessed in chronic primary insomniacs using two concurrent, multi-center, randomized, double-blind, Latin Square crossover studies. Study 1 (n = 47) compared zaleplon (10 and 40 mg) to triazolam (0.25 mg) and placebo. Study 2 (n = 36) compared zaleplon (20 and 60 mg) to triazolam (0.25 mg) and placebo. For each study, polysomnographically recorded sleep parameters and patient reports of sleep quality were collected during baseline and two consecutive nights during the four treatment phases in each study. All doses of zaleplon produced significant decreases in latency to persistent sleep. Although no minimally effective dose could be determined, dose-response effects were apparent. Triazolam 0.25 mg produced a decrease in latency to persistent sleep that was comparable to that of zaleplon 10 mg. Only the triazolam dose and the 60 mg dose of zaleplon produced significant increases in total sleep time over placebo. Zaleplon 40 and 60 mg and triazolam produced decreases in the percentage of REM sleep compared to placebo. Patient reports of efficacy were consistent with objective findings. In addition, all doses of zaleplon tended to increase while triazolam decreased the percentage of stage 3/4 sleep. There was no evidence of residual daytime impairment for any of the zaleplon doses, however, triazolam administration produced significant impairment in performance on a digit copying test. A higher number of adverse events were seen with the 40 and 60 mg doses of zaleplon compared to triazolam (0.25) and placebo. At higher doses, zaleplon is more effective than triazolam at reducing latency to persistent sleep in chronic insomnia and is not associated with the decrease in slow-wave sleep or residual impairment observed with triazolam. However, increases in total sleep time were apparent only at doses which produced concomitant increases in the number of adverse events. In contrast, triazolam (0.25 mg) produced increases in total sleep time (;25 min) and decreases in latency to persistent sleep at a dose of 0.25 mg. Copyright 2000 John Wiley & Sons, Ltd.
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PMID:Dose-response effects of zaleplon as compared with triazolam (0.25 mg) and placebo in chronic primary insomnia. 1240 12

Insomnia affects 30-35% of people living in developed countries. The impact of insomnia on daytime functioning and its relationship with medical and psychiatric illnesses necessitate early treatment to prevent insomnia becoming persistent and to avoid the development of complications. However, pharmacological strategies must achieve a balance between sedative and adverse effects. In the last 30 years, benzodiazepines have been the preferred drugs for the treatment of insomnia. Benzodiazepines act nonselectively at two central receptor sites, named omega(1) and omega(2), which are located in different areas of the CNS. The sedative action of benzodiazepines is related to omega(1) receptors, whereas omega(2) receptors are responsible for their effects on memory and cognitive functioning. According to their pharmacokinetic profile, benzodiazepines can be classified into three groups: short half-life (<3 hours), medium half-life (8-24 hours) and long half-life (>24 hours). The newer non-benzodiazepine agents zopiclone, zolpidem and zaleplon have a hypnosedative action comparable with that of benzodiazepines, but they display specific pharmacokinetic and pharmacodynamic properties. These three 'Z' agents all share a short plasma half-life and limited duration of action. In addition, these agents are selective compounds that interact preferentially with omega(1) receptors (sedative effect), whereas benzodiazepines also interact with omega(2) receptors (adverse effects on cognitive performance and memory). Zaleplon is characterised by an ultrashort half-life (approximately 1 hour). Zolpidem and zopiclone have longer half-lives (approximately 2.4 and 5 hours, respectively). These properties, together with the low risk of residual effect, may explain the limited negative influences of these agents on daytime performance. Psychomotor tasks and memory capacities appear to be better preserved by non-benzodiazepine agents than by benzodiazepines. When present, cognitive deficits almost exclusively coincide with the peak plasma concentration. In particular, impairment can emerge in the first hours after drug administration, whereas psychomotor and memory tests carried out 7-8 hours later (i.e. in the morning) generally show no relevant alterations. As with benzodiazepines, the three 'Z' non-benzodiazepine agents should be used for a limited period, even in chronic relapsing conditions. Further evaluation is needed of the safety of hypnosedative medications in the long-term management of insomnia.
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PMID:New drugs for insomnia: comparative tolerability of zopiclone, zolpidem and zaleplon. 1260 88

Zaleplon ("Sonata") is a pyrazolopyrimidine derivative approved for use in the United States for the treatment of insomnia. To date, there has been little data in the toxicological literature where zaleplon has been implicated as causing a fatal intoxication, either alone or in combination with other drugs. This report documents a case where zaleplon was identified in a suicide by multiple drug ingestion. The following zaleplon concentrations were found: heart blood 2.2mg/l; bile 8.6mg/l and urine 1.4mg/l. Zaleplon was also detected but not quantitated in the kidney and liver.
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PMID:Mixed drug intoxication involving zaleplon ("Sonata"). 1285 Apr 5

Benzodiazepines have historically been the mainstay of treatment for sleeping disorders, yet they have many shortcomings. A new group of sedative hypnotic agents has been developed for this purpose. Similar to the benzodiazepines, zaleplon, zolpidem and zopiclone have activity at the GABA receptor complex, yet they appear to have more selectivity for certain subunits of the GABA receptor. This produces a clinical profile that is more efficacious with fewer side effects. Zaleplon, zolpidem and zopiclone are structurally distinct. Due to variation in binding to the GABA receptor subunits, these three compounds show subtle differences in their effect on sleep stages, and as antiepileptics, anxiolytics and amnestics. The duration of action of zaleplon, zolpidem and zopiclone can be related to their individual pharmacokinetic profile, which subsequently determines the time course of drug effect. Each of these compounds has a unique pharmacokinetic profile with different bioavailability, volume of distribution and elimination half-lives. Zaleplon has a rapid elimination so there are fewer residual side effects after taking a single dose at bedtime. By comparison, zolpidem and zopiclone have a more delayed elimination so there may be a prolonged drug effect. This can result in residual sedation and side effects but may be useful for sustained treatment of insomnia with less waking during the night. There are also differences in potency based on plasma concentrations suggesting that there are differences in binding to the GABA receptor complex. Although zaleplon has a much lower bioavailability (30%), the treatment dose is similar to zolpidem and zopiclone (bioavilaibility of 70%) because of the increased potency of zaleplon. The pharmacokinetics and pharmacodynamics of zaleplon, zolpidem and zopiclone are significantly different from benzodiazepines. The new drugs are sufficiently unique from each other to allow customisation of treatment for various types of insomnia. While zaleplon may be best indicated for the delayed onset of sleep, zolpidem and zopiclone may be better indicated for maintaining a complete night's sleep. Only the patient's symptoms and response to treatment will dictate the best course of treatment.
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PMID:Comparative pharmacokinetics and pharmacodynamics of short-acting hypnosedatives: zaleplon, zolpidem and zopiclone. 1500 37

BACKGROUND: Insomnia is a prevalent medical disorder that has significant effects on occupational performance, health, and quality of life. Insomnia places an enormous burden on society through increased visits to physicians, loss of productivity in the workplace, and an increased rate of accidents. An estimated sum of $100 million is spent each year on direct treatment of unresolved insomnia. Physicians need to initiate early effective treatment to prevent development of chronic insomnia and its associated morbidity. Institution of good sleep hygiene practices may be useful in some patients but may not be adequate for resolution of all sleep problems. Behavioral treatments, while effective and durable, are time consuming and not widely utilized in clinical practice. Pharmacotherapy includes benzodiazepine hypnotics, but concerns regarding adverse effects (e.g., residual sedation) prompted the search for safer options. DATA SOURCES: Published and presented studies containing clinical data on zaleplon, a new nonbenzodiazepine sleep medication, were identified via MEDLINE, Current Contents (ISI database), bibliographic reviews, and consultation with sleep specialists. RESULTS: Zaleplon effectively shortens sleep onset time and improves the quality of sleep in patients with insomnia. Whether administered at bedtime or later at night, zaleplon is devoid of residual sedative effects that impair next-day functioning. Follow-up studies evaluating the long-term efficacy and safety of zaleplon showed that decreased time to sleep onset was maintained during therapy lasting up to 52 weeks, without a withdrawal syndrome after discontinuation. CONCLUSION: Insomnia is recurrent and unpredictable in nature. Despite the long-term morbidity of this sleep disorder, research evidence and practice guidelines have not explored long-term use of hypnotics. Many patients could benefit from long-term drug therapy with a sleep medication that is devoid of residual effects and can be taken at bedtime or later as symptoms occur, rather than nightly in anticipation of a sleep problem.
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PMID:The Importance of Residual Effects When Choosing a Hypnotic: The Unique Profile of Zaleplon. 1501 16

BACKGROUND: Insomnia is a very common symptom, particularly in the elderly. Thus, all hypnotic medications should be carefully evaluated in the elderly population. Zaleplon, a new nonbenzodiazepine hypnotic with a short elimination half-life (approximately 1 hour), was evaluated in the current study. METHOD: This multicenter, randomized, placebo-controlled outpatient study evaluated the efficacy and safety of zaleplon, 5 and 10 mg, in elderly patients with insomnia (as defined by DSM-IV); zolpidem, 5 mg, was the active comparator. Sleep was assessed in 549 elderly patients (>/= 65 years old) by using morning questionnaires completed after each of 7 baseline nights during which placebo was given, 14 nights of double-blind treatment, and 7 nights of placebo after discontinuation of active treatment. RESULTS: Zaleplon, 10 mg, and zolpidem, 5 mg, significantly reduced sleep latency during both weeks of the study. Zaleplon, 5 mg, reduced sleep latency only during week 2. Sleep duration was increased with zolpidem, 5 mg, during weeks 1 and 2 and with zaleplon, 10 mg, during week 1. No clinically significant rebound insomnia was observed after discontinuation of treatment with zaleplon, whereas evidence of rebound effects was seen with zolpidem. There was no significant difference between either zaleplon dose and placebo in the frequency of any central nervous system adverse events. CONCLUSION: Zaleplon is effective in reducing latency to sleep without evidence of undesired effects in elderly patients with insomnia.
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PMID:Zaleplon, A Novel Nonbenzodiazepine Hypnotic, Effectively Treats Insomnia in Elderly Patients Without Causing Rebound Effects. 1501 84


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