"This novel non-benzodiazepine sleep aid provides a new option for the millions of Americans with chronic insomnia. Unlike all other available prescription sleep aids, which are generally indicated for short-term use, eszopiclone has been studied and approved for use when longer-term treatment is needed," said Andrew Krystal, M.D., Director of the Sleep Disorder Research Laboratory and Insomnia Program at Duke University Medical Center, Durham, NC. "The six-month, double-blind, placebo-controlled study of eszopiclone provides unprecedented evidence of sustained efficacy. There were statistically significant improvements in patient-reported measures of sleep onset and sleep maintenance versus placebo for the entire duration of the study with no evidence of tolerance."
"The approval of LUNESTA makes an important treatment option available for patients who have trouble sleeping. Insomnia can include difficulty falling asleep and/or staying asleep. LUNESTA is an important advance for doctors and patients alike, as it can provide sleep efficacy, even over the long term," said Thomas Roth, Ph.D., Director of the Sleep Disorders and Research Center at Henry Ford Hospital, Detroit.
"We are very excited about the commercial launch of LUNESTA, which will take place in early January 2005. Sepracor's sales force, which includes approximately 1,250 sales professionals, is trained and ready to promote LUNESTA to primary care doctors, CNS specialists including psychiatrists, and hospitals in the U.S.," said W. James O'Shea, President and Chief Operating Officer at Sepracor. "We believe that LUNESTA, with its differentiated product label, will provide physicians with a unique treatment option for their insomnia patients, particularly those with sleep maintenance difficulties and those who suffer chronically." An excellent write up on Lunesta can be found at the Sepracor's website the writeup on Lunesta a nonbendodiazepine hynotic agent.
Sleep Med. 2005 Jan;6(1):15-22. Epub 2004 Dec 25.
An assessment of the efficacy and safety of eszopiclone in the treatment of transient insomnia in healthy adults.
Rosenberg R, Caron J, Roth T, Amato D.
Northside Hospital Sleep Medicine Institute, 5780 Peachtree Dunwoody Road, Suite 150, Atlanta, GA 30342, USA.
BACKGROUND AND PURPOSE: This randomized, double-blind, placebo-controlled study assessed the efficacy and safety of eszopiclone, a non-benzodiazepine hypnotic agent, in healthy adults using the first-night effect model of transient insomnia. PATIENTS AND METHODS: A total of 436 healthy, normal sleeping participants were randomized to receive either eszopiclone 1, 2, 3, or 3.5mg, or placebo. Efficacy and next-morning effects were evaluated via polysomnography (PSG), Digit Symbol Substitution Test (DSST), and self-report. RESULTS: Patients treated with eszopiclone had significantly less PSG latency to persistent sleep (all doses except 1mg; P Hum Psychopharmacol. 2004 Jul;19(5):305-22. :
Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis.
Dundar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T.
The University of Liverpool, Faculty of Medicine, Liverpool Reviews and Implementation Group, The Sherrington Buildings, Ashton Street, Liverpool L69 3GE, UK.
yenal@liv.ac.uk
OBJECTIVES: To compare the clinical effectiveness of zaleplon, zolpidem or zopiclone (Z-drugs) with either benzodiazepines licensed and approved for use in the UK for the short-term management of insomnia (diazepam, loprazolam, lorazepam, lormetazepam, nitrazepam, temazepam) or with each other. METHODS: MEDLINE, EMBASE, PsycINFO, Science Citation Index/Web of Science were searched from 1966 to March 2003 and The Cochrane Library, reference lists of included studies and a number of psychopharmacology journals. Randomized controlled trials comparing either benzodiazepines with the Z-drugs or any two of the Z-drugs in patients with insomnia were included. Outcome measures included: sleep onset latency, total sleep duration, number of awakenings, quality of sleep, adverse events, tolerance, rebound insomnia and daytime alertness. RESULTS AND CONCLUSIONS: Twenty four eligible studies were identified with a total study population of 3,909 (17 studies comparing a Z-drug with a benzodiazepine and 7 comparing a Z-drug). Insufficient or inappropriately reported data meant that meta-analysis was possible only for a small number of outcomes. There are few clear, consistent differences between the drugs. Some evidence suggests that zaleplon gives shorter sleep latency but shorter duration of sleep than zolpidem, reflecting the pharmacological profiles of the drugs. Copyright 2004 John Wiley & Sons, Ltd.
Am J Phys Med Rehabil. 2004 Jun;83(6):421-7.
: Comparison of lorazepam and zopiclone for insomnia in patients with stroke and brain injury: a randomized, crossover, double-blinded trial.
Li Pi Shan RS, Ashworth NL.
Department of Physical Medicine and Rehabilitation, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
OBJECTIVES: To determine if lorazepam or zopiclone is more effective in providing a restful night of sleep and to assess the effects of these medications on cognition. DESIGN: A randomized, double-blinded, crossover trial was performed at a tertiary care rehabilitation inpatient unit in a teaching hospital. A total of 18 brain-injured and stroke patients, aged 20-78 yrs, were administered lorazepam, 0.5-1.0 mg, orally at bedtime as needed for 7 days and zopiclone, 3.75-7.5 mg, orally at bedtime as needed for 7 days. Total sleep time and characteristics of sleep were measured. Effects on cognition were also measured using the Folstein Mini Mental Status Exam. RESULTS: There was no difference in average sleep duration or in subjective measures of sleep. Cognition as assessed by the Mini Mental Status Exam revealed no difference in the zopiclone arm compared with the lorazepam arm. CONCLUSION: Zopiclone is equally effective as lorazepam in the treatment of insomnia in stroke and brain-injured patients.
Aviat Space Environ Med. 2004 Jun;75(6):512-9.
Related Articles, Links Sleep-inducing pharmaceuticals: a comparison of melatonin, zaleplon, zopiclone, and temazepam.
Paul MA, Gray G, MacLellan M, Pigeau RA.
Defence Research and Development Canada Toronto, North York, Ontario, Canada.
mpaul@drdc-rddc.gc.ca
INTRODUCTION: Current military operations often require pharmaceutical methods to sustain alertness and facilitate sleep in order to maintain operational readiness. This study was designed to compare the sleep-inducing power of four medications. METHOD: There were 9 men and 14 women, ages 21-53 yr, who were assessed for psychomotor performance before and for 7 h after ingestion of a single dose of placebo, zaleplon 10 mg, zopiclone 7.5 mg, temazepam 15 mg, or time-released melatonin 6 mg. The experimental design was a double-blind crossover with counterbalanced treatment order. Subjects wore polysomnographic electrodes to record total sleep and sleep latency during 4-min periods with eyes closed immediately before and after each psychomotor test sequence. Subjective drowsiness was assessed by questionnaire. RESULTS: There were drug x trials interactions for zaleplon, zopiclone, and temazepam for total sleep, sleep latency, and subjective drowsiness. More sleep, shorter sleep latency, and more drowsiness occurred immediately after psychomotor testing compared to before testing for all medications. Melatonin did not cause any sleep prior to psychomotor testing sessions, but caused sleep and reduced sleep latency after psychomotor test sessions from 1 3/4 h to 4 3/4 h post-ingestion. CONCLUSIONS: The sleep-inducing power of the medications before psychomotor testing was zopiclone > zaleplon > melatonin > temazepam. The corresponding effect after psychomotor testing was zopiclone > melatonin > zaleplon > temazepam.
Aviat Space Environ Med. 2004 May;75(5):439-43.
Related Articles, Links Melatonin and zopiclone as facilitators of early circadian sleep in operational air transport crews.
Paul MA, Gray G, Sardana TM, Pigeau RA.
Defence Research and Development Canada-Toronto, North York, Ontario, Canada.
michel.paul@drdc-rddc.gc.ca
INTRODUCTION: This study was an extension into an operational setting of previous laboratory work investigating the use of zopiclone and melatonin to facilitate early circadian sleep in transport aircrew. The previous laboratory-based study demonstrated that both melatonin and zopiclone were effective in inducing early circadian sleep without impacting on psychomotor performance after a 7-h sleep period. METHODS: In a repeated measures, placebo-controlled protocol, 30 aircrew flew 3 transatlantic missions over which they took each of the 3 medications (placebo, sustained-release melatonin 2 mg, or zopiclone 5 mg) at an early body clock time (17:00) during their first stopover. They wore wrist actigraphs prior to and throughout the missions, took a single dose of their scheduled medication immediately prior to their early circadian bedtime, and completed a sleep questionnaire on arising from their medicated sleep. RESULTS: The results of the actigraphic data show that relative to placebo, aircrew on melatonin and zopiclone fell asleep more quickly (melatonin: p < 0.01, zopiclone: p < 0.003), slept more (melatonin: p < 0.02, zopiclone: p < 0.005), had fewer awakenings after sleep onset (melatonin: p < 0.004, zopiclone: p < 0.01), and spent less time awake after sleep onset (melatonin: p < 0.01, zopiclone: p < 0.05). The results of the questionnaire data show that relative to placebo, aircrew on melatonin and zopiclone experienced less difficulty getting to sleep (melatonin: p < 0.0001, zopiclone: p < 0.001), had fewer awakenings (melatonin: p < 0.005, zopiclone: p < 0.001), less difficulty returning to sleep after awakening (melatonin: p < 0.0001, zopiclone: p < 0.0001), and reported a better sleep quality (melatonin: p < 0.0003, zopiclone: p < 0.0004). There were no statistically significant differences between melatonin and zopiclone in any of the actigraphic or questionnaire sleep parameters. CONCLUSIONS: Melatonin and zopiclone, in the dosages we used, are equipotent facilitators of early circadian sleep during transmeridian air transport operations
Clin Pharmacokinet. 2004;43(4):227-38. : Comparative pharmacokinetics and pharmacodynamics of short-acting hypnosedatives: zaleplon, zolpidem and zopiclone.
Drover DR.
Department of Anesthesia, Stanford University School of Medicine, Stanford, California, USA.
ddrover@stanford.edu
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.
CNS Drugs. 2004;18 Suppl 1:9-15; discussion 41, 43-5. : The pharmacology and mechanisms of action of new generation, non-benzodiazepine hypnotic agents.
Sanger DJ.
Sanofi-Synthelabo, Paris, France.
david.sanger@sanofi-synthelabo.com
The new generation hypnotic drugs, zolpidem, zopiclone and zaleplon, are at least as efficacious in the clinic as benzodiazepines and may offer advantages in terms of safety. These drugs act through the BZ binding sites associated with GABAA receptors, but show some differences from benzodiazepines in pharmacological effects and mechanisms of action. Of particular interest is the finding that zolpidem shows a wide separation between doses producing sedative effects and those giving rise to other behavioural actions, and induces less tolerance and dependence than benzodiazepines. Zolpidem also demonstrates selectivity for GABAA receptors containing alpha1 subunits. Recent studies using genetically modified mice have confirmed that receptors containing alpha1 subunits play a particularly important role in mediating sedative activity, thus providing an explanation for the pharmacological profile of zolpidem.
Aviat Space Environ Med. 2003 Dec;74(12):1263-70.: Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor performance.
Paul MA, Gray G, Kenny G, Pigeau RA.
Toronto laboratories of Defence Research and Development Canada, Toronto, Ontario, Canada.
michel.paul@drdc-rddc.gc.ca
INTRODUCTION: Modern military operations may require pharmaceutical methods to sustain alertness and facilitate sleep in order to maintain operational readiness. In operations with very limited sleep windows, hypnotics with very short half-lives (e.g., zaleplon, t(1/2) 1 h) are of interest, while with longer sleep opportunities, longer acting agents (e.g., zopiclone, temazepam (t(1/2) 4-6 hours) may be used. This study was designed to compare the effect of a single dose of zaleplon, zopiclone, temazepam, and melatonin on psychomotor performance and to quantify the post-ingestion time required for return to normal performance. METHOD: There were 23 subjects (9 men, 14 women), 21-53 yr of age, assessed for psychomotor performance on 2 test batteries (4 tasks) that included a sleepiness questionnaire. Psychomotor testing was conducted prior to, and for 7 h after, ingestion of a single dose of each of placebo, zaleplon 10 mg, zopiclone 7.5 mg, temazepam 15 mg, and time-released melatonin 6 mg. The experimental design was a double-blind cross-over with counter-balanced treatment order. RESULTS: Zaleplon, zopiclone, and temazepam impaired performance on all four tasks: serial reaction time (SRT), logical reasoning (LRT), serial subtraction (SST), and multitask (MT). Melatonin did not impair performance on any task. The time to recovery of normal performance for SRT during the zaleplon, zopiclone and temazepam conditions were 3.25, 6.25, and 5.25 h respectively; for LRT were 3.25, >6.25, and 4.25 h; for SST were 2.25, >6.25, and 4.25 h, and for MT were 2.25, 4.25, and 3.25 h. The recovery time to baseline subjective sleepiness levels for zaleplon, zopiclone, temazepam, and melatonin were 4.25, >6.25, 5.25, and >4.25 h, respectively. CONCLUSIONS: In spite of a prolonged period of perceived sleepiness, melatonin was superior to zaleplon in causing no impact on performance. The remaining drugs listed in increasing order of performance impact duration are zaleplon, temazepam, and zopiclone.
good overview on Lunesta