Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia
Columbia University College of Physicians and Surgeons, New York 10025, USA. Current Medical Research and Opinion
(Impact Factor: 2.65).
12/2004; 20(12):1979-91. DOI: 10.1185/174234304X15174
Eszopiclone is a new, single-isomer, non-benzodiazepine, cyclopyrrolone agent under investigation for the treatment of insomnia. The present study was a randomized, double-blind, multicenter, placebo-controlled trial conducted to assess the efficacy and safety of eszopiclone in adults with chronic primary insomnia.
Patients (n = 308) were randomized to receive placebo or eszopiclone (2 mg or 3 mg) for 44 consecutive nights, followed by 2 nights of single-blind placebo. Efficacy was evaluated with polysomnography (Nights 1, 15 and 29) and patient-reports (Nights 1, 15, 29 and 43/44). Next-day residual effects were evaluated using the Digit-Symbol Substitution Test (DSST).
Eszopiclone 3 mg had significantly less time to sleep onset (p < or = 0.0001), more total sleep time and sleep efficiency (p < or = 0.0001), better sleep maintenance (p < or = 0.01), and enhanced quality and depth of sleep (p < 0.05) across the double-blind period compared with placebo. Eszopiclone 2 mg had significantly less time to sleep onset (p < or = 0.001), more total sleep time (p < or = 0.01) and sleep efficiency (p < or = 0.001), and enhanced quality and depth of sleep (p < 0.05) compared with placebo, but did not significantly improve sleep maintenance. There was no evidence of tolerance or rebound insomnia after therapy discontinuation. Median DSST scores showed no decrement in psychomotor performance relative to baseline and did not differ from placebo in either eszopiclone group. Treatment was well tolerated; the most common adverse event related to eszopiclone was unpleasant taste.
Patients treated with nightly eszopiclone 3 mg had better polysomnographic (through Night 29) and patient-reported measures (through Night 44) of sleep over the 6-week trial. There was no evidence of tolerance or rebound insomnia and no detrimental effects on next-day psychomotor performance using the DSST.
Available from: ncbi.nlm.nih.gov
- "In 2004, eszopiclone was approved by the US Food and Drug Administration for the treatment of insomnia in elderly and nonelderly adults [6,8]. The clinical studies used for registration in the United States included both short- and long-term studies but did not include long-term studies in elderly patients [9-13]. Overall outcomes in these studies showed that eszopiclone significantly reduced sleep latency (SL), increased total sleep time (TST), reduced wake time after sleep onset (WASO), and was generally well tolerated compared with placebo [8-13]. "
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ABSTRACT: The primary objective of this study was to evaluate long-term (24-week) safety of eszopiclone in elderly and nonelderly Japanese patients with chronic insomnia. The secondary objectives were to evaluate short-term (4-week) efficacy and to assess for rebound insomnia or dependence after long-term treatment.
Patients (n = 164 elderly; n = 161 nonelderly), with or without psychiatric comorbidities, were randomized to receive low-dose (1 mg, elderly; 2 mg, nonelderly) or high-dose (2 mg, elderly; 3 mg, nonelderly) eszopiclone. The safety evaluation included adverse events, vital signs, clinical laboratory parameters, and electrocardiogram. Efficacy was assessed using patient reports of sleep latency (SL), total sleep time (TST), wake time after sleep onset (WASO), number of awakenings (NA), quality of sleep, depth of sleep, daytime sleepiness, daytime ability to function, and the 36-item Short Form (SF-36) Health Survey.
The rate of adverse events was 81.5% in the 1-mg elderly group, 79.5% in the 2-mg elderly group, 82.1% in the 2-mg nonelderly group, and 87.0% in the 3-mg nonelderly group. Dysgeusia was the most common adverse event and was dose-related. Of 12 serious adverse events, none were considered by the investigator to be related to study medication. No rebound insomnia was observed. Eszopiclone significantly improved SL, TST, WASO, NA, and daytime sleepiness and function from baseline to Week 4, irrespective of age and psychiatric comorbidity. Improvements were also observed in SF-36 Mental Health Component scores in elderly and nonelderly patients with psychiatric comorbidities.
Irrespective of age, eszopiclone appeared safe as administered in this study for 24 weeks. Eszopiclone improved sleep variables in insomnia patients with and without psychiatric disorders and health-related quality of life in those with psychiatric disorders.
ClinicalTrials.gov #NCT00770692; http://clinicaltrials.gov/ct2/show/NCT00770692.
Available from: Jaime Monti
- "In some studies, the effi cacy has been assessed using both polysomnography (PSG) and subjective self reports (Zammit et al 2004; Rosenberg et al 2005; Roth et al 2005; McCall et al 2006; Soares et al 2006). The effi cacy endpoints included sleep onset latency (SOL), wake time after sleep onset (WASO), total sleep time (TST), number of awakenings, sleep effi ciency (SE), quality of sleep, daytime ability to function, daytime alertness, and sense of physical well-being (Zammit et al 2004; Rosenberg et al 2005). Various populations were included in the studies that assessed the effi cacy and safety of eszopiclone: healthy volunteers, non-elderly, and elderly subjects with chronic primary insomnia, and patients with major depressive disorder (MDD) and comorbid insomnia (Rosenberg et al 2005; Zammit et al 2006). "
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ABSTRACT: 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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