eszopiclone and Sleep-Initiation-and-Maintenance-Disorders

Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently used worldwide. We aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder.. In this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials. We included studies comparing pharmacological treatments or placebo as monotherapy for the treatment of adults (≥18 year) with insomnia disorder. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Primary outcomes were efficacy (ie, quality of sleep measured by any self-rated scale), treatment discontinuation for any reason and due to side-effects specifically, and safety (ie, number of patients with at least one adverse event) both for acute and long-term treatment. We estimated summary standardised mean differences (SMDs) and odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with Open Science Framework, https://doi.org/10.17605/OSF.IO/PU4QJ.. We included 170 trials (36 interventions and 47 950 participants) in the systematic review and 154 double-blind, randomised controlled trials (30 interventions and 44 089 participants) were eligible for the network meta-analysis. In terms of acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo (SMD range: 0·36-0·83 [CINeMA estimates of certainty: high to moderate]). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27-0·71 [moderate to very low]). Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (OR 0·72 [95% CI 0·52-0·99; moderate], 0·70 [0·51-0·95; moderate] and 0·71 [0·52-0·98; moderate], respectively). Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00 [95% CI 1·28-3·13; very low]; zolpidem: 1·79 [1·25-2·50; moderate]); and zopiclone caused more dropouts than did eszopiclone (OR 1·82 [95% CI 1·01-3·33; low]), daridorexant (3·45 [1·41-8·33; low), and suvorexant (3·13 [1·47-6·67; low]). For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27-2·78 [high to very low]). For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63 [95% CI 0·36-0·90; very low]; lemborexant: 0·41 [0·04-0·78; very low]) and eszopiclone was more effective than ramelteon (0.63 [0·16-1·10; very low]) and zolpidem (0·60 [0·00-1·20; very low]). Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43 [95% CI 0·20-0·93; very low]; zolpidem: 0·43 [0·19-0·95; very low]); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00 [95% CI 1·11-3·70; very low]).. Overall, eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Doxepin, seltorexant, and zaleplon were well tolerated, but data on efficacy and other important outcomes were scarce and do not allow firm conclusions. Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits. These results should serve evidence-based clinical practice.. UK National Institute for Health Research Oxford Health Biomedical Research Centre.

Topics: Adult; Benzodiazepines; Doxepin; Eszopiclone; Humans; Melatonin; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Zolpidem

The purpose of this study was to compare the effectiveness of the only Food and Drug Administration-authorized prescription digital therapeutic (PDT) Somryst versus face-to-face cognitive behavioral therapy for insomnia (CBT-I), or FDA-approved prescription medications for insomnia.. A systematic literature review was undertaken to identify relevant studies. A Bayesian network meta-analysis (NMA) was conducted to examine (1) mean change in insomnia severity index (ISI); (2) proportional change in ISI remitters; (3) mean change in wake after sleep onset (WASO); and (4) mean change in sleep onset latency (SOL).. Twenty studies provided data on the PDT, CBT-I, CBT-I in combination with self-help (SH), or two prescription medications (eszopiclone and zolpidem). The PDT was associated with significant mean change in ISI (-5.77, 95% Credible Interval [CrI] - 8.53, -3.07) and ISI remitters (OR 12.33; 95% CrI 2.28, 155.91) compared to placebo, and had the highest probability of being the most effective treatment overall for ISI mean change (56%), and ISI remitters (64%). All evaluated interventions significantly outperformed placebo for WASO but no significant differences were observed for SOL (five interventions). Sensitivity analyses excluding medications and meta-regression (assessing type, duration, delivery method for CBT-I) did not affect NMA results.. This network meta-analysis demonstrated that a PDT delivering CBT-I had the highest probability of being most effective compared to face-to-face CBT-I, prescription sleep medications, or placebo, as measured by reductions in mean ISI score from baseline and ISI-determined remittance.. Chronic insomnia is the long-term inability to fall asleep easily or to stay asleep. This condition is much more serious than most people realize, raising the risk of many health problems including depression, heart disease, and injuries.Although sleep medications are commonly used to treat insomnia, these drugs may not be effective and can lead to harms such as accidents or clouded thinking. Clinical guidelines recommend a treatment called cognitive behavioral therapy for insomnia (CBT-I) that is safe and effective. Unfortunately, there is a shortage of clinicians trained to provide CBT-I.Prescription digital therapeutics (PDTs) are FDA-approved software programs available on mobile devices such as smartphones. A PDT for insomnia (Somryst) delivers CBT-I and can overcome barriers to access for this important type of therapy. To compare the effectiveness of this PDT with FDA-approved sleep medications and face-to-face CBT-I a special kind of study was conducted called a network meta-analysis. This is a statistical method of combining data from numerous studies in a way that allows the results to be fairly compared.This network meta-analysis of 20 studies found that the PDT was more effective at reducing insomnia symptoms than any of the sleep medications studied and was even more effective than face-to-face CBT-I as measured by scores on a clinically valid scale of insomnia symptoms. These results are encouraging because they suggest that digital delivery of CBT-I could help the millions of people who currently do not have access to this effective treatment.

Topics: Adult; Bayes Theorem; Cognitive Behavioral Therapy; Eszopiclone; Humans; Network Meta-Analysis; Prescriptions; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Zolpidem

To compare the efficacy and safety of various hypnotics for identifying the best treatments for insomnia in older adults.. We searched the EMBASE, PubMed, ClinicalTrials.gov, and ProQuest Dissertations and Theses A&I databases from the inception to September 12, 2020. Only randomized controlled trials comparing hypnotics with either another hypnotic or placebo for insomnia treatment in elderly people were included. Sleep outcomes, including total sleep time, sleep onset latency, wake after sleep onset, sleep efficiency, were derived from polysomnography, valid questionnaires, or sleep diaries.. We identified 24 articles with 5917 older adults. Eszopiclone and low-dose doxepin were ranked the optimal therapy for prolonging objective and subjective total sleep time (26.69 and 28.19 min), respectively, compared to placebo. Zaleplon was the most effective therapy in reducing objective and subjective sleep onset latency (-21.63 and -15.86 min) compared with control. Temazepam was the best treatment for objective and subjective wake after sleep onset (-25.29 and -22.25 min) compared with control. Low-dose doxepin appeared to be the effective treatment for increasing objective sleep efficiency (6.08%) Triazolam showed the higher risk of overall adverse events (odds ratio, 1.96, 95% confidence interval 1.03-3.74) when compared to zaleplon.. Considering study quality and the potential adverse effects of benzodiazepines and nonbenzodiazepines, low-dose doxepin seems to be the optimal pharmacotherapy for the improvements in total sleep time and sleep efficiency. Future RCTs investigating the treatment effects of hypnotics, particularly low-dose doxepin, on insomnia in older adults are warranted. PROSPERO Registration number: CRD42016046301.

Topics: Aged; Eszopiclone; Humans; Hypnotics and Sedatives; Network Meta-Analysis; Sleep; Sleep Initiation and Maintenance Disorders

To identify and analyze postmarketing cases of complex sleep behaviors (CSBs) resulting in serious injuries, including death, associated with eszopiclone, zaleplon, or zolpidem (Z-drugs).. Retrospective analysis of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from 16 December 1992 through 27 February 2018 and medical literature using PubMed and EMBASE. We used random sampling and descriptive statistics.. We identified 66 cases that met inclusion and exclusion criteria, four of which were identified in the medical literature. Twenty cases reported death and 46 cases reported serious injuries in association with CSBs occurring after the use of a Z-drug. Fatal cases described events, such as carbon monoxide poisoning, drowning, falls, hypothermia, motor vehicle collisions, and apparent completed suicide. Nonfatal cases resulting in serious injuries described events, such as accidental overdoses, falls, gunshot wounds, hypothermia, third-degree burns, and self-injuries or suicide attempts. Twenty-two cases reported a previous episode of a CSB while taking a Z-drug prior to the event reported in this case series.. The FAERS and medical literature cases support the need for increased awareness of the consequences that may occur because of CSBs associated with the use of Z-drugs. Therefore, to protect public health, regulatory actions were taken, including adding a Boxed Warning, a Contraindication in patients who have experienced a prior episode of a CSB with a Z-drug, and updating the existing Warnings and Precautions. An FDA Drug Safety Communication was also disseminated to alert healthcare professionals and the public of this potential risk.

Topics: Acetamides; Adult; Adverse Drug Reaction Reporting Systems; Aged; Drug Labeling; Eszopiclone; Female; Humans; Male; Middle Aged; Parasomnias; Pyrimidines; Retrospective Studies; Risk Assessment; Risk Factors; Sleep; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Somnambulism; Time Factors; Treatment Outcome; Wounds and Injuries; Zolpidem

Although different forms of pharmacological intervention are often prescribed for insomnia disorder, the comparative efficacies among various drugs remain unclear. We therefore conducted this study to quantitatively compare the efficacy of various pharmacotherapies for insomnia by modeling.. We searched PubMed, EMBASE and Cochrane Library databases for randomized placebo-controlled trials of insomnia medications that were conducted within a designated time period (from the inception dates to May 16, 2019). Pharmacodynamic models were established to describe the time course of changes from baseline in selected sleep parameters. Sleep quality and dropout rates were also compared by a single-arm meta-analysis.. In sum, 43 studies covering 44 trials (14,535 patients) were included in the analysis. The drugs evaluated included flurazepam, quazepam, temazepam, triazolam, eszopiclone, zaleplon, zolpidem, extended-release zolpidem, suvorexant, ramelteon and doxepin. The established models revealed eszopiclone had the highest efficacy in terms of sleep latency (SL), total sleep time (TST), and sleep quality, and was also associated with the lowest dropout rates. The effect of suvorexant on the parameter 'wake after sleep onset' (WASO) was significantly higher than that of the other drugs analyzed.. Each drug has its own characteristics in the treatment of insomnia, and this needs to be taken into consideration to meet individual clinical needs. These results serve as a quantitative supplement for clinical practice by reflecting the difference in efficacy of various drugs in the treatment of insomnia.

Topics: Eszopiclone; Humans; Hypnotics and Sedatives; Pharmaceutical Preparations; Sleep Initiation and Maintenance Disorders; Zolpidem

In this study, we performed a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials to evaluate the efficacy and safety of eszopiclone for the treatment of primary insomnia.. We searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials and PubMed from inception to June 2018. Additionally, we searched the ClinicalTrials.gov trials register for other relevant trials. According to participants, intervention, comparison, outcome (PICO) criteria, studies were included that focused on: adults diagnosed with primary insomnia, aged 18-65 and > 65 years; eszopiclone for the treatment of primary insomnia; comparison were made between eszopiclone and placebo; as well as primary outcomes, secondary outcomes, and adverse effects.. A total of six randomized trials involving 2809 patients with primary insomnia were included in our analysis. Our analysis suggested that eszopiclone was associated with significant improvements in subjective sleep latency, wake after sleep onset, number of awakenings, total sleep time at one week, two weeks, one month, three months and six months. Meanwhile, eszopiclone was associated with increased quality of sleep, ability to function, daytime alertness and sense of physical well-being at one week, one month, three months and six months. Dizziness and unpleasant taste were the most common adverse effects in elderly subgroup. Alternately, non-elderly patients may be more prone to adverse effects such as infection, pharyngitis, somnolence, unpleasant taste and dry mouth.. This meta-analysis showed that eszopiclone is an effective and safe therapy option for patients with primary insomnia, especially in elderly patients. However, due to the high clinical heterogeneity in some outcomes, further standardized preparation, large-scale and rigorously designed trials are needed.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Double-Blind Method; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Placebos; Randomized Controlled Trials as Topic; Safety; Sleep; Sleep Initiation and Maintenance Disorders; Sleep Latency; Treatment Outcome

Insomnia is a common feature of schizophrenia. Although several studies have been published about the influence of certain drugs on schizophrenia patients' sleep, there are no well-grounded recommendations about insomnia treatment in this clinical setting. The present review aimed to identify relevant empirical evidence on available treatments of insomnia in patients with schizophrenia, assessing their safety and efficacy.. This is a systematic review of clinical trials investigating the effect of treatments for insomnia in patients with a diagnosis of schizophrenia. Data were obtained from Medline/PubMed, Embase, PsycInfo, and the Cochrane Library. Risk of bias was assessed in individual studies for selection, performance, detection, attrition, and reporting bias.. Four studies met inclusion criteria; 2 using melatonin, 1 using paliperidone, and 1 with eszopiclone. All reported positive results: melatonin increased sleep efficiency and total duration of sleep; paliperidone decreased sleep latency onset and increased total sleep time and sleep efficiency; eszopiclone decreased insomnia severity index.. Despite a very limited number of specific studies on this matter, all 4 studies have shown good benefit/risk ratios and reviewed options-melatonin, paliperidone, and eszopiclone-might represent valid options for residual insomnia in schizophrenia.

Topics: Eszopiclone; Humans; Hypnotics and Sedatives; Melatonin; Odds Ratio; Paliperidone Palmitate; Schizophrenia; Sleep Initiation and Maintenance Disorders

zolpidem, zopiclone, eszopiclone and zaleplon, also known as 'Z-drugs', are commonly used as alternatives to benzodiazepines (BZDs) to treat insomnia. Z-drugs are often perceived as safer than BZDs. We conducted a systematic review and meta-analysis evaluating the association between Z-drugs and fracutres, falls and injuries.. a systematic review was performed using MEDLINE, EMBASE and ClinicalTials.gov. Pooled effect-sizes were calculated comparing Z-drugs users with non-users, using fixed and random-effect models with corresponding 95% confidence of intervals (CI).. we identified 14 eligible studies reporting on the association between Z-drugs and outcomes of interest. Z-Drugs were associated with a statistically significant increased risk for fractures, with evidence of considerable heterogeneity (OR = 1.63; 95% CI: 1.42-1.87; I2 = 90%; n = 830,877). Likewise, there was a trend suggesting a 2-fold increase in the odds for falls, however, this result was not statistically significant and there was evidence of considerable heterogeneity (OR = 2.40; 95% CI: 0.92-6.27; I2 = 95%; n = 19,505). In an analysis assessing the risk for injuries following exposure to zolpidem we found a statistically significant increased risk of injuries, with no evidence of heterogeneity (OR = 2.05; CI 95%: 1.95-2.15; I2 = 0; n = 160,502). Results were similar in sensitivity analyses, including analyses restricted to studies of high-quality, studies with control groups suffering from insomnia, and with specific Z-drugs.. our results indicate that Z-drugs are associated with an increased risk for fractures, and suggest a possible increased risk for falls and injuries as well. However, studies included were observational and susceptible to confounding. Physicians should consider these potential risks before prescribing these medications in older adults.

Topics: Accidental Falls; Acetamides; Adult; Age Factors; Aged; Aged, 80 and over; Aging; Azabicyclo Compounds; Eszopiclone; Fractures, Bone; Humans; Middle Aged; Piperazines; Pyrimidines; Risk Assessment; Risk Factors; Sleep; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Zolpidem

Insomnia is a major public health issue affecting between 6% to 10% of the adult population in Western countries. Eszopiclone is a hypnotic drug belonging to a newer group of hypnotic agents, known as new generation hypnotics, which was marketed as being just as effective as benzodiazepines for this condition, while being safer and having a lower risk for abuse and dependence. It is the aim of the review to integrate evidence from randomised controlled trials and to draw conclusions on eszopiclone's efficacy and safety profile, while taking methodological features and bias risks into consideration.. To assess the efficacy and safety of eszopiclone for the treatment of insomnia compared to placebo or active control.. We searched the Cochrane Central Register of Controlled trials (CENTRAL), MEDLINE, Embase, PsycINFO, PSYNDEX and registry databases (WHO trials portal, ClinicalTrials.gov) with results incorporated from searches to 10 February 2016. To identify trials not registered in electronic databases, we contacted key informants and searched reference lists of identified studies. We ran an update search (21 February 2018) and have placed studies of interest in awaiting classification/ongoing studies. These will be incorporated into the next version of the review, as appropriate.. Parallel group randomised controlled trials (RCTs) comparing eszopiclone with either placebo or active control were included in the review. Participants were adults with insomnia, as diagnosed with a standardised diagnostic system, including primary insomnia and comorbid insomnia.. Two authors independently extracted outcome data; one reviewer assessed trial quality and the second author cross-checked it.. A total of 14 RCTs, with 4732 participants, were included in this review covering short-term (≤ 4 weeks; 6 studies), medium-term (> 4 weeks ≤ 6 months; 6 studies) and long-term treatment (> 6 months; 2 studies) with eszopiclone. Most RCTs included in the review included participants aged between 18 and 64 years, three RCTs only included elderly participants (64 to 85 years) and one RCT included participants with a broader age range (35 to 85 years). Seven studies considered primary insomnia; the remaining studies considered secondary insomnia comorbid with depression (2), generalised anxiety (1), back pain (1), Parkinson's disease (1), rheumatoid arthritis (1) and menopausal transition (1).Meta-analytic integrations of participant-reported data on sleep efficacy outcomes demonstrated better results for eszopiclone compared to placebo: a 12-minute decrease of sleep onset latency (mean difference (MD) -11.94 min, 95% confidence interval (CI) -16.03 to -7.86; 9 studies, 2890 participants, moderate quality evidence), a 17-minute decrease of wake time after sleep onset (MD -17.02 min, 95% CI -24.89 to -9.15; 8 studies, 2295 participants, moderate quality evidence) and a 28-minute increase of total sleep time (MD 27.70 min, 95% CI 20.30 to 35.09; 10 studies, 2965 participants, moderate quality evidence). There were no significant changes from baseline to the first three nights after drug discontinuation for sleep onset latency (MD 17.00 min, 95% CI -4.29 to 38.29; 1 study, 291 participants, low quality evidence) and wake time after sleep onset (MD -6.71 min, 95% CI -21.25 to 7.83; 1 study, 291 participants, low quality evidence). Adverse events during treatment that were documented more frequently under eszopiclone compared to placebo included unpleasant taste (risk difference (RD) 0.18, 95% CI 0.14 to 0.21; 9 studies, 3787 participants), dry mouth (RD 0.04, 95% CI 0.02 to 0.06; 6 studies, 2802 participants), somnolence (RD 0.04, 95% CI 0.02 to 0.06; 8 studies, 3532 participants) and dizziness (RD 0.03, 95% CI 0.01 to 0.05; 7 studies, 2933 participants). According to the GRADE criteria, evidence was rated as being of moderate quality for sleep efficacy outcomes and adverse events and of low quality for rebound effects and next-day functioning.. Eszopiclone appears to be an efficient drug with moderate effects on sleep onset and maintenance. There was no or little evidence of harm if taken as recommended. However, as certain patient subgroups were underrepresented in RCTs included in the review, findings might not have displayed the entire spectrum of possible adverse events. Further, increased caution is required in elderly individuals with cognitive and motor impairments and individuals who are at increased risk of using eszopiclone in a non-recommended way.

Topics: Adult; Aged; Aged, 80 and over; Eszopiclone; Humans; Hypnotics and Sedatives; Middle Aged; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Time Factors; Treatment Outcome

A large proportion of paediatric patients with attention-deficit/hyperactivity disorder (ADHD) have associated sleep problems which not only affect the child's wellbeing but also impact family functioning. Management of sleep problems is consequently an important aspect of overall ADHD management in paediatric patients. Although some drugs are being used off-label for the management of paediatric insomnia, there is scant clinical evidence supporting their use. Our aim was to identify and assess the quality of published studies reporting the safety, tolerability and efficacy of drugs used for treating behavioural insomnia in children with ADHD.. After an initial screen to determine which drugs were most commonly used, we conducted a systematic review of English-language publications from searches of PubMed, EMBASE, PsycINFO and two trial register databases to February 2017, using keywords 'clonidine', 'melatonin', 'zolpidem', 'eszopiclone', 'L-theanine', 'guanfacine', 'ADHD', 'sleep disorder' and 'children'. For quality assessment of included studies, we used the CONSORT checklist for randomised control trials (RCTs) and the Downs and Black checklist for non-RCTs.. Twelve studies were included. Two case series for clonidine, two RCTs and four observational studies for melatonin and one RCT each for zolpidem, eszopiclone, L-theanine and guanfacine. Of the 12 included studies, only one on eszopiclone scored excellent for quality. The quality of the rest of the studies varied from moderate to low. For clonidine, melatonin and L-theanine, improvements in sleep-onset latency and total sleep duration were reported; however, zolpidem, eszopiclone and guanfacine failed to show any improvement when compared with placebo. Clonidine, melatonin, L-theanine, eszopiclone and guanfacine were well tolerated with mild to moderate adverse events; zolpidem was associated with neuropsychiatric adverse effects.. There is generally poor evidence for prescribing drugs for behavioural insomnia in children with ADHD. Further controlled studies are warranted.

Topics: Attention Deficit Disorder with Hyperactivity; Child; Clonidine; Eszopiclone; Glutamates; Guanfacine; Humans; Melatonin; Observational Studies as Topic; Pyridines; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Zolpidem

No systematic reviews and meta-analyses on the use of Z-drug for schizophrenia are available. Randomized, placebo-controlled, or non-pharmacological intervention-controlled trials published before 03/20/2017 were retrieved from major healthcare databases and clinical trial registries. A meta-analysis including only randomized, placebo-controlled trials was performed. Efficacy outcomes were measured as improvement in overall schizophrenia symptoms, total sleep time, and wake after sleep onset. Safety/acceptability outcomes were discontinuation rate and individual adverse events. Four trials [1 alpidem placebo-controlled study (n=66), 2 eszopiclone placebo-controlled studies (n=60), and 1 eszopiclone, shallow needling-controlled study (n=96)] were identified. The meta-analysis showed no significant differences in any outcome between pooled Z-drug and placebo treatment groups. For individual studies, alpidem was superior to placebo in improving the overall schizophrenia symptoms. One of the eszopiclone studies showed that eszopiclone was superior to placebo in improving the Insomnia Severity Index scores. Another eszopiclone study showed that eszopiclone did not differ from shallow needling therapy in improving both schizophrenia- and insomnia-related symptoms. Although this study failed to show significant benefits for the use of Z-drug in the treatment of schizophrenia, it showed that short-term use of eszopiclone is an acceptable method for treating persistent insomnia among these patients.

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Imidazoles; Male; Middle Aged; Pyridines; Randomized Controlled Trials as Topic; Schizophrenia; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Young Adult

Topics: Acetamides; Animals; Eszopiclone; Humans; Hypnotics and Sedatives; Plant Preparations; Pyridines; Pyrimidines; Sleep Initiation and Maintenance Disorders; Somnambulism; Zolpidem

To investigate the effectiveness of non-benzodiazepine hypnotics (Z drugs) and associated placebo responses in adults and to evaluate potential moderators of effectiveness in a dataset used to approve these drugs.. Systematic review and meta-analysis.. US Food and Drug Administration (FDA).. Randomised double blind parallel placebo controlled trials of currently approved Z drugs (eszopiclone, zaleplon, and zolpidem).. Change score from baseline to post-test for drug and placebo groups; drug efficacy analysed as the difference of both change scores. Weighted raw and standardised mean differences with their confidence intervals under random effects assumptions for polysomnographic and subjective sleep latency, as primary outcomes. Secondary outcomes included waking after sleep onset, number of awakenings, total sleep time, sleep efficiency, and subjective sleep quality. Weighted least square regression analysis was used to explain heterogeneity of drug effects.. 13 studies containing 65 separate drug-placebo comparisons by type of outcome, type of drug, and dose were included. Studies included 4378 participants from different countries and varying drug doses, lengths of treatment, and study years. Z drugs showed significant, albeit small, improvements (reductions) in our primary outcomes: polysomnographic sleep latency (weighted standardised mean difference, 95% confidence interval -0.57 to -0.16) and subjective sleep latency (-0.33, -0.62 to -0.04) compared with placebo. Analyses of weighted mean raw differences showed that Z drugs decreased polysomnographic sleep latency by 22 minutes (-33 to -11 minutes) compared with placebo. Although no significant effects were found in secondary outcomes, there were insufficient studies reporting these outcomes to allow firm conclusions. Moderator analyses indicated that sleep latency was more likely to be reduced in studies published earlier, with larger drug doses, with longer duration of treatment, with a greater proportion of younger and/or female patients, and with zolpidem.. Compared with placebo, Z drugs produce slight improvements in subjective and polysomnographic sleep latency, especially with larger doses and regardless of type of drug. Although the drug effect and the placebo response were rather small and of questionable clinical importance, the two together produced to a reasonably large clinical response.

Topics: Acetamides; Adult; Aged; Azabicyclo Compounds; Confidence Intervals; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Piperazines; Polysomnography; Pyridines; Pyrimidines; Sleep Initiation and Maintenance Disorders; Treatment Outcome; United States; United States Food and Drug Administration; Zolpidem

Eszopiclone is the single (S)-enantiomer of the cyclopyrrolone hypnotic zopiclone. It was marketed in the U.S. in December 2004. Its kinetics and possible mode of action, pivotal regulatory trials and its use in insomnia comorbid with other conditions are reviewed, together with trials in patients with obstructive sleep apnea syndromes. Safety and tolerability aspects are discussed, including its dysgeusic profile and effects on memory, cognitive and psychomotor function. U.S.-based pharmacoeconomic data are included together with the design features of key regulatory studies submitted for regulatory approval in Japan.

Topics: Adult; Aged; Animals; Azabicyclo Compounds; Clinical Trials as Topic; Cognition; Drug Approval; Eszopiclone; Humans; Hypnotics and Sedatives; Japan; Memory; Middle Aged; Piperazines; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive; Sleep Initiation and Maintenance Disorders

Insomnia is a common and underdiagnosed condition that can result in significant economic and clinical consequences. Despite numerous behavioral and pharmacotherapeutic treatment options available for insomnia, few receive adequate treatment, and sleep maintenance (staying asleep) remains a significant problem. To date, available sedative-hypnotic agents have limitations that have lead to inadequate treatment of insomnia. This review provides an overview of eszopiclone and its role in the treatment of insomnia.. Electronic databases (MEDLINE, EMBASE, International Pharmaceutical Abstracts) were searched for applicable primary literature and review articles.. Mechanisms of action at the gamma-amino butyric acid (GABA) receptor sites and pharmacologic and pharmacokinetic characteristics are presented. Eszopiclone, a nonbenzodiazepine S-enantiomer of racemic zopiclone, is highlighted as the first sedative-hypnotic agent to be approved by the United States Food and Drug Administration for the treatment of sleep onset latency and sleep maintenance insomnia with no short-term restrictions. Recently, the European Medicines Agency recommended marketing authorization of eszopiclone.. Eszopiclone has been shown to be an efficacious and cost-effective option for the treatment of transient and chronic insomnia in adults.

Topics: Acute Disease; Adult; Aged; Azabicyclo Compounds; Chronic Disease; Comorbidity; Cost-Benefit Analysis; Drug Interactions; Eszopiclone; GABA-A Receptor Agonists; Humans; Hypnotics and Sedatives; Piperazines; Receptors, Melatonin; Safety; Sleep Initiation and Maintenance Disorders; Treatment Outcome; United States; United States Food and Drug Administration

Eszopiclone (Lunesta), the S-enantiomer of racemic zopiclone, is a nonbenzodiazepine hypnotic agent that is approved in the US as an oral, once-nightly therapy for insomnia in adults; eszopiclone is also currently under review by the European Medicines Agency. Eszopiclone is rapidly absorbed after oral administration without any next-day clinical residual effects being detected. Large, well designed trials of up to 6 months' duration have shown that eszopiclone significantly improves both sleep onset and sleep maintenance compared with placebo in adult and elderly patients with primary insomnia. Eszopiclone for 4-8 weeks also significantly improved sleep parameters compared with placebo in patients with insomnia coexisting with other conditions that also disturb sleep (co-morbid insomnia), and improved certain measures of the co-morbid conditions to a greater extent than the standard therapies alone. Short-term eszopiclone produced improvements in daytime functioning in patients with co-morbid insomnia. Six months' therapy in adults with primary insomnia improved daytime functioning and health-related quality of life. Eszopiclone was generally well tolerated. There was no evidence of tolerance during 12 months' treatment with this agent. On discontinuation of eszopiclone, there was no rebound insomnia or serious withdrawal effects. Well designed, comparative trials with other nonbenzodiazepine hypnotics are needed to determine its relative efficacy and tolerability. A cost-utility analysis suggested that eszopiclone is cost effective for the treatment of primary insomnia in the US. Therefore, eszopiclone is a useful therapeutic option in the management of adult and elderly patients with primary or co-morbid insomnia. Unlike most other hypnotics, eszopiclone is not limited to short-term use.

Topics: Adult; Azabicyclo Compounds; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Interactions; Eszopiclone; Humans; Hypnotics and Sedatives; Patient Satisfaction; Piperazines; Sleep Initiation and Maintenance Disorders

Given the well-established problems with sleep at high altitude, it is not uncommon for people planning trips to the mountains to seek advice from clinicians regarding pharmacologic options for improving sleep during their trip. This review article considers the various medications that have been studied for this purpose at high altitude with an emphasis on both their efficacy and safety. The available data support the use of either acetazolamide, temazepam, zolpidem or zaleplon in this environment. Other agents commonly used at sea-level such as eszopiclone and diphenhydramine have not been studied at high altitude but are likely safe to use given their mechanism of action and known side effects. Limited evidence suggests diazepam may cause hypoventilation at high altitude and its use in this environment should be discouraged. Insufficient data exist to determine which agent is most effective at altitude nor do we know whether combination therapy with acetazolamide and a hypnotic agent offers any benefits over monotherapy.

Topics: Acetamides; Acetazolamide; Altitude Sickness; Anti-Anxiety Agents; Azabicyclo Compounds; Benzodiazepines; Diphenhydramine; Eszopiclone; GABA Agonists; Humans; Hypnotics and Sedatives; Mountaineering; Piperazines; Pyridines; Pyrimidines; Sleep Initiation and Maintenance Disorders; Sleep Stages; Temazepam; Wakefulness; Zolpidem

Hypnotics are commonly use in the treatment of insomnia, and hypnotic use among older adults is more prevalent than with younger adults. Unfortunately, the use of hypnotics is not well studied in the ever-growing geriatric population and the magnitude of the medication benefit is usually not impressive. Insomnia in older adults is usually treated with benzodiazepines, nonbenzodiazepines, and other agents, such as trazodone, valerian, and melatonin. Using appropriately selected agents and therapy initiated with a low dose and careful monitoring of the patient could minimize common unwanted side effects.

Topics: Antidepressive Agents; Azabicyclo Compounds; Central Nervous System Depressants; Eszopiclone; GABA Agonists; GABA-A Receptor Antagonists; Humans; Indenes; Melatonin; Phytotherapy; Piperazines; Pyridines; Sleep Initiation and Maintenance Disorders; Valerian; Zolpidem

Insomnia, the most common sleep disturbance in later life, affects 20%-50% of older adults. Eszopiclone, a short-acting nonbenzodiazepine hypnotic agent developed for the treatment of insomnia, has been available in Europe since 1992 and in the US since 2005. Although not yet evaluated for transient insomnia in older adults, eszopiclone has been shown to be safe and efficacious for short-term treatment (2 weeks) of chronic, primary insomnia in older adults (64-91 years). Clinical studies in younger adults (mean = 44 years) have shown eszopiclone can be used for 6-12 months without evidence of problems. Because the oldest participant in these longer-term trials was 69, it not known whether eszopiclone is effective for older adults [particularly the old old (75-84 years) and oldest old (85+)] when used over longer periods. This is unfortunate, because older individuals frequently suffer from chronic insomnia. Cognitive-behavioral therapy for insomnia, which effectively targets the behavioral factors that maintain chronic insomnia, represents an attractive treatment alternative or adjuvant to eszopiclone for older adults. To date, no studies have compared eszopiclone to other hypnotic medications or to nonpharmacological interventions, such as cognitive-behavioral therapy for insomnia, in older adults. All of the clinical trials reported herein were funded by Sepracor. This paper provides an overview of the literature on eszopiclone with special emphasis on its use for the treatment of late-life insomnia. Specific topics covered include pharmacology, pharmacodynamics, pharmacokinetics, clinical trial data, adverse events, drug interactions, tolerance/dependence, and economics/cost considerations for older adults.

Topics: Adult; Age of Onset; Aged; Aged, 80 and over; Azabicyclo Compounds; Chronic Disease; Cognitive Behavioral Therapy; Drug Costs; Drug Interactions; Drug Tolerance; Eszopiclone; Humans; Hypnotics and Sedatives; Middle Aged; Piperazines; Sleep Initiation and Maintenance Disorders; Substance-Related Disorders; Treatment Outcome

To investigate the effects of eszopiclone on sleep quality and cognitive function in elderly patients with Alzheimer's disease (AD) and sleep disorders.. This study was a prospective study of 96 elderly patients with AD and sleep disturbance treated in our hospital from April 2019 to December 2020. All patients were divided into a control group (48 patients, given alprazolam tablets) and a study group (48 patients, given eszopiclone) according to the random number table method.. After treatment, compared with the control group, the study group had lower sleep latency, daytime function, sleep disturbance, sleep efficiency, sleep quality, sleeping time, and hypnotic medication scores (p < .05). After treatment, sleep progression and sleep architecture improvement were more obvious in the study group compared with the control group (p < .05). After treatment, compared with the control group, the rhythm disturbance, psychotic disorder, hallucination, phobic anxiety, and disorder in the study group improved more significantly (p < .05). After treatment, compared with the control group, the scores of orientation, attention, memory, calculation, recall, and language ability in the study group improved more significantly (p < .05). After treatment, the scores of the physical life self-care scale and instrumental activities of daily living scale in the study group were improved more obviously compared with the control group, with significant differences (p < .05).. Eszopiclone can effectively improve the quality of sleep and cognitive function in elderly patients with AD and sleep disorder.

Topics: Activities of Daily Living; Aged; Alzheimer Disease; Cognition; Double-Blind Method; Eszopiclone; Humans; Hypnotics and Sedatives; Prospective Studies; Sleep Initiation and Maintenance Disorders; Sleep Quality; Sleep Wake Disorders; Treatment Outcome

To determine the therapeutic effects of two selective GABA-A agonists, zopiclone and eszopiclone, in the treatment of insomnia.. This study comprised a phase III, single-center, randomized, double-blind, double-dummy, parallel-group, non-inferiority trial. Patients were randomized to receive zopiclone 7.5 mg or eszopiclone 3 mg, both orally, for four weeks. In total, 199 patients were evaluated during two visits and then followed for at least six weeks. The primary endpoint was the Insomnia Severity Index after four weeks of treatment. Secondary endpoints were obtained through polysomnography data, including total sleep time, sleep latency and sleep efficiency. The frequency of adverse events was also analyzed. ClinicalTrials.gov: NCT01100164.. The primary efficacy analysis demonstrated the non-inferiority of eszopiclone over zopiclone. Analysis of objective parameters assessed by polysomnography showed that eszopiclone increased total sleep time and also improved sleep efficiency. The safety profile of both study treatments was similar and the most common events reported in both groups were dysgeusia, headache, dizziness, irritability and nausea. Adverse events were observed in 223 patients, 109 (85.2%) in the eszopiclone group and 114 (87.7%) in the zopiclone group.. Based on the Insomnia Severity Index at the end of four weeks of treatment, eszopiclone demonstrated efficacy comparable to that of zopiclone in the treatment of insomnia, increasing total sleep time as well as sleep efficiency according to polysomnography.

Topics: Adult; Azabicyclo Compounds; Double-Blind Method; Dysgeusia; Eszopiclone; Female; Headache; Humans; Hypnotics and Sedatives; Male; Middle Aged; Piperazines; Polysomnography; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Young Adult

A review on headache and insomnia revealed that insomnia is a risk factor for increased headache frequency and headache intensity in migraineurs. The authors designed a randomized, double blind, placebo-controlled, parallel-group, pilot study in which migraineurs who also had insomnia were enrolled, to test this observation.. In the study, the authors treated 79 subjects with IHS-II migraine with and/or without aura and with DSM-IV primary insomnia for 6 weeks with 3 mg eszopiclone (Lunesta(®)) or placebo at bedtime. The treatment was preceded by a 2-week baseline period and followed by a 2-week run-out period.. Of the 79 subjects treated, 75 were evaluable, 35 in the eszopiclone group, and 40 in the placebo group. At baseline, the groups were comparable except for sleep latency. Of the three remaining sleep variables, total sleep time, nighttime awakenings, and sleep quality, the number of nighttime awakenings during the 6-week treatment period was significantly lower in the eszopiclone group than in the placebo group (P = 0.03). Of the three daytime variables, alertness, fatigue, and functioning, this was also the case for fatigue (P = 005). The headache variables, frequency, duration, and intensity, did not show a difference from placebo during the 6-week treatment period.. The study did not meet primary endpoint, that is, the difference in total sleep time during the 6-week treatment period between eszopiclone and placebo was less than 40 minutes. Therefore, it failed to answer the question as to whether insomnia is, indeed, a risk factor for increased headache frequency and headache intensity in migraineurs.

Topics: Adolescent; Adult; Azabicyclo Compounds; Double-Blind Method; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Migraine Disorders; Pilot Projects; Piperazines; Risk Factors; Sleep Initiation and Maintenance Disorders; Treatment Outcome

To identify whether baseline demographic factors or subjective sleep variables are associated with the outcomes following treatment with eszopiclone using data from a recent randomized controlled trial of 78 Japanese subjects with insomnia who were treated with 2 mg eszopiclone per day.. We performed a post hoc analysis of factors including sleep latency (SL), wake time after sleep onset (WASO) (both assessed via sleep diaries), and several demographic variables. Subjects with a SL or WASO > 30 min at baseline and with evaluable SL/WASO data at Week 4 were included in SL and WASO remitter analyses, respectively; those with a SL or WASO ≤ 30 min at Week 4 were defined as SL or WASO remitters, respectively. Threshold baseline SL and WASO values for identification of remitters were determined.. No relationships between subjectively assessed therapeutic outcomes and demographic factors were identified. Patients with shorter SL and lower WASO values at baseline showed better outcomes following treatment with eszopiclone in terms of SL and WASO changes, respectively. Baseline SL of 75 min and baseline WASO of 80 min were selected as arbitrary cutoff values for determination of SL and WASO remitters/non-remitters, respectively.. These findings may help clinicians to predict their patients' outcomes in response to standard doses of eszopiclone in clinical practice.

Topics: Adult; Age Factors; Aged; Chronic Disease; Double-Blind Method; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Japan; Male; Middle Aged; Severity of Illness Index; Sex Factors; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Wakefulness; Young Adult

Insomnia, which is very common in patients with chronic low back pain (LBP), has long been viewed as a pain symptom that did not merit specific treatment. Recent data suggest that adding insomnia therapy to pain-targeted treatment should improve outcome; however, this has not been empirically tested in LBP or in any pain condition treated with a standardized pain medication regimen. We sought to test the hypothesis that adding insomnia therapy to pain-targeted treatment might improve sleep and pain in LBP.. Double-blind, placebo-controlled, parallel-group, 1-mo trial.. Duke University Medical Center Outpatient Sleep Clinic.. Fifty-two adult volunteers with LBP of at least 3 mo duration who met diagnostic criteria for insomnia (mean age: 42.5 y; 63% females).. Subjects were randomized to eszopiclone (ESZ) 3 mg plus naproxen 500 mg BID or matching placebo plus naproxen 500 mg twice a day.. ESZ SIGNIFICANTLY IMPROVED TOTAL SLEEP TIME (MEAN INCREASE: ESZ, 95 min; placebo, 9 min) (primary outcome) and nearly all sleep measures as well as visual analog scale pain (mean decrease: ESZ, 17 mm; placebo, 2 mm) (primary pain outcome), and depression (mean Hamilton Depression Rating Scale improvement ESZ, 3.8; placebo, 0.4) compared with placebo. Changes in pain ratings were significantly correlated with changes in sleep.. The addition of insomnia-specific therapy to a standardized naproxen pain regimen significantly improves sleep, pain, and depression in patients with chronic low back pain (LBP). The findings indicate the importance of administering both sleep and pain-directed therapies to patients with LBP in clinical practice and provide strong evidence that improving sleep disturbance may improve pain.. clinicaltrials.gov identifier: NCT00365976.

Topics: Adult; Azabicyclo Compounds; Double-Blind Method; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Low Back Pain; Male; Middle Aged; Pain Measurement; Piperazines; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Young Adult

To evaluate efficacy and safety of eszopiclone compared with placebo in children and adolescents with insomnia associated with attention-deficit/hyperactivity disorder (ADHD).. A 12-week, randomized, double-blind, placebo-controlled trial evaluated efficacy and safety of high- or low-dose eszopiclone (1 or 2 mg in children aged 6-11 years, 2 or 3 mg in children ages 12-17 years), given every evening, in 486 patients with ADHD-related insomnia. The primary efficacy variable was change in latency to persistent sleep from baseline to week 12, based on polysomnography. Key secondary measures were polysomnography-measured wake time after sleep onset, Clinical Global Impression Parent/Caregiver and Child scales, and the Conners' ADHD rating scales. The safety of eszopiclone was further studied over 1 year of open-label treatment in 55 patients who completed the double-blind study, and 249 patients with no previous eszopiclone exposure.. Neither low-dose nor high-dose eszopiclone significantly reduced latency to persistent sleep compared with placebo after 12 weeks of treatment. Secondary outcomes were considered nonsignificant based on the hierarchical statistical analysis plan. The most frequent treatment-emergent adverse events over 12 weeks with eszopiclone were headache, dysgeusia, and dizziness. The study results demonstrated that eszopiclone was well tolerated over 1 year of treatment, with 11.2% of patients discontinuing open-label treatment because of an adverse event.. Eszopiclone (up to 3 mg) failed to reduce latency to persistent sleep on polysomnography after 12 weeks in children aged 6 to 17 years with ADHD-related insomnia. Eszopiclone was well tolerated in the 1-year study.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Azabicyclo Compounds; Child; Dose-Response Relationship, Drug; Double-Blind Method; Eszopiclone; Female; Follow-Up Studies; Humans; Hypnotics and Sedatives; Male; Piperazines; Polysomnography; Single-Blind Method; Sleep Initiation and Maintenance Disorders

Insomnia is frequent in schizophrenia and may contribute to cognitive impairment as well as overuse of weight inducing sedative antipsychotics. We investigated the effects of eszopiclone on sleep and cognition for patients with schizophrenia-related insomnia in a double-blind placebo controlled study, followed by a two-week, single-blind placebo phase.. Thirty-nine clinically stable outpatients with schizophrenia or schizoaffective disorder and insomnia were randomized to either 3mg eszopiclone (n=20) or placebo (n=19). Primary outcome measure was change in Insomnia Severity Index (ISI) over 8 weeks. Secondary outcome measure was change in MATRICS Consensus Cognitive Battery (MATRICS). Sleep diaries, psychiatric symptoms, and quality of life were also monitored.. ISI significantly improved more in eszopiclone (mean=-10.7, 95% CI=-13.2; -8.2) than in placebo (mean=-6.9, 95% CI=-9.5; -4.3) with a between-group difference of -3.8 (95% CI=-7.5; -0.2). MATRICS score change did not differ between groups. On further analysis there was a significant improvement in the working memory test, letter-number span component of MATRICS (mean=9.8±9.2, z=-2.00, p=0.045) only for subjects with schizophrenia on eszopiclone. There were improvements in sleep diary items in both groups with no between-group differences. Psychiatric symptoms remained stable. Discontinuation rates were similar. Sleep remained improved during single-blind placebo phase after eszopiclone was stopped, but the working memory improvement in patients with schizophrenia was not durable.. Eszopiclone stands as a safe and effective alternative for the treatment of insomnia in patients with schizophrenia. Its effects on cognition require further study.

Topics: Azabicyclo Compounds; Cognition; Double-Blind Method; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Medical Records; Middle Aged; Patient Dropouts; Piperazines; Psychotic Disorders; Quality of Life; Schizophrenia; Schizophrenic Psychology; Single-Blind Method; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome

This study examined changes in sleep parameters between the laboratory and the home setting before and after laboratory monitoring in depressed insomniacs undergoing treatment.. This study was a post hoc analysis of a double-blind, randomized, placebo-controlled clinical trial performed with 60 depressed, insomniac outpatients. Patients underwent actigraphic monitoring along with sleep diaries over a continuous 2-week period. After one week of baseline monitoring, subjects spent one night in the laboratory with concurrent actigraphic and PSG monitoring with sleep diaries. Actigraphic monitoring and sleep diaries were continued for another week at home, along with initiation of open-label fluoxetine (FLX).. Actigraphically recorded laboratory sleep during the night in the laboratory was found to be improved relative to actigraphically recorded sleep at home, with less wake time and greater sleep time and sleep efficiency occurring in the laboratory. In contrast, sleep diaries indicated a slight worsening of sleep in the laboratory compared to home, with significantly more awakenings in the laboratory compared to the week at home before and after the laboratory night.. The differences between objective and subjective sleep measurements seen in depressed insomniacs may be influenced by the monitoring setting and measurement modality.. ClinicalTrials.gov Identifier: NCT00247624.

Topics: Actigraphy; Adult; Antidepressive Agents, Second-Generation; Azabicyclo Compounds; Depressive Disorder, Major; Double-Blind Method; Eszopiclone; Female; Fluoxetine; Humans; Hypnotics and Sedatives; Male; Middle Aged; Piperazines; Polysomnography; Self-Assessment; Sleep; Sleep Initiation and Maintenance Disorders; Young Adult

Insomnia marked by sleep maintenance difficulty is extremely prevalent. Yet, problems staying asleep have been relatively neglected as a research focus compared to problems falling asleep. Insomnia treatment studies typically have not required participants to have a problem specifically with sleep maintenance. It is possible that exclusion of such subjects limits the detection of treatment effects in the overall trial in general, and of effects on sleep maintenance specifically. In order to address these issues we conducted a post hoc analysis of a 6-month placebo-controlled trial in which there were no inclusion criteria that specified sleep maintenance difficulties to assess the variable effects of baseline wake time after sleep onset (WASO - the primary maintenance measure) on the efficacy of eszopiclone 3mg.. Patients diagnosed with chronic primary insomnia were randomized to eszopiclone 3mg (n=593) or placebo (n=195) nightly for six months. The present analyses of this study consisted of: (1) determination of the distribution of baseline WASO; (2) continuous analysis of the relationship between baseline WASO severity and drug-placebo difference at month 1 and 6; and (3) categorical efficacy analyses of subgroups delimited by the following WASO thresholds: 0, 30, 45, 60, and 90 min.. The baseline WASO distribution was: ≤ 30=32.2%; >0 to ≤ 45=41.5%; >30 to ≤ 90=33.0%; >45 to ≤ 90=23.7%; >90=22.6%. A relationship between greater baseline WASO severity and a significantly greater drug-placebo difference in efficacy for WASO was evident in both continuous and categorical analyses. Eszopiclone was found to have significant sleep maintenance efficacy at each time point across the entire range of WASO severity studied.. As illustrated in this analysis, a significant proportion of chronic insomnia patients in efficacy trials that select on the basis of sleep onset latency and total sleep time criteria may have normative-range WASO. However, even in the subgroup with minimal WASO there was a significant sleep maintenance effect. The absence of any sleep maintenance effect in a drug trial may reflect the inclusion of relatively many insomnia patients with no baseline WASO abnormality. However, treatments with therapeutic effects on sleep maintenance, can still demonstrate improvement in sleep maintenance, even in a population not selected for this type of sleep problem, if adequately powered. Future clinical trials intending to examine sleep maintenance should employ WASO selection criteria that would ensure sufficient power to detect a sleep maintenance effect. Drug-placebo difference increased as a function of baseline WASO severity, suggesting that eszopiclone's clinical effectiveness for insomnia may be enhanced in patients with more severe sleep maintenance symptoms.

Topics: Adult; Aged; Azabicyclo Compounds; Chronic Disease; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Piperazines; Placebos; Severity of Illness Index; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Young Adult

To evaluate the efficacy and dose-response effect of eszopiclone on sleep latency and sleep maintenance in Japanese patients with primary insomnia.. In this randomized, double-blind, five-way crossover study, 72 patients received placebo, eszopiclone 1mg, 2mg, and 3mg, and zolpidem 10mg in random order for two consecutive nights with a washout period between treatments. Objective sleep measures from polysomnography (PSG) and subjective patient reports were collected.. All active treatments produced significant improvement in objective and subjective sleep latency compared with placebo (P<0.05 for all comparisons); linear dose-response relationships were observed for eszopiclone. PSG-determined wake time after sleep onset (WASO), sleep efficiency, and number of awakenings (NA), and patient-reported measures of WASO, NA, sleep quality, sleep depth, and daytime functioning significantly improved following treatment with eszopiclone 2mg and 3mg and zolpidem 10mg versus placebo (P<0.05). Eszopiclone at all doses increased total sleep time and stage 2 sleep time (P<0.001 for both comparisons), but did not alter REM or slow-wave sleep. Eszopiclone was generally well tolerated; the most frequently reported adverse event was mild dysgeusia.. In Japanese patients with primary insomnia, eszopiclone 2mg and 3mg significantly improved PSG-determined and patient-reported sleep latency and sleep maintenance relative to placebo.

Topics: Adult; Azabicyclo Compounds; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Japan; Male; Middle Aged; Piperazines; Polysomnography; Sleep Initiation and Maintenance Disorders; Young Adult

Patients with major depressive disorder (MDD) and significant anxiety are less responsive to antidepressants than those without anxiety. In this post hoc analysis of patients with insomnia and comorbid anxious depression, eszopiclone cotherapy with a selective serotonin reuptake inhibitor (SSRI) was compared with placebo cotherapy.. Data were pooled from 2 randomized, double-blind, 8-week trials. One trial (conducted from January 2004 to October 2004) included patients with DSM-IV insomnia and comorbid MDD treated with fluoxetine concurrently with eszopiclone 3 mg/d or placebo. The other trial (conducted from July 2005 to April 2006) included patients with DSM-IV-TR insomnia and comorbid generalized anxiety disorder treated with escitalopram concurrently with eszopiclone 3 mg/d or placebo. Anxious depression was defined as a baseline 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 14 (excluding insomnia items) and an anxiety/somatization factor score ≥ 7. Treatment group differences were determined for mean changes in HDRS-17 scores (with and without insomnia items), HDRS anxiety/somatization scores, and response and remission rates. Severity of insomnia was assessed by the Insomnia Severity Index (ISI).. In the combined dataset, 347 of 1,136 patients (30.5%) had insomnia and comorbid anxious depression. Significant improvements in insomnia were observed for eszopiclone cotherapy relative to placebo cotherapy (mean change from baseline on the ISI: -11.0 vs -7.8, respectively; P < .001). There were greater reductions in HDRS-17 scores at week 8 following cotherapy with eszopiclone compared with placebo when the insomnia items were included (mean change: -14.1 vs -11.2, respectively; P < .01) or excluded (-10.6 vs -8.9; P < .01), but not for anxiety/somatization (-4.3 vs -4.1; P = .23). Response rates were greater for eszopiclone cotherapy than for placebo cotherapy (55.6% vs 42.0%, respectively; P = .01; 50.0% vs 44.4% when insomnia items were removed; P = .3). Remission rates were not significantly different (32.6% vs 27.2%, respectively; P = .28).. In this post hoc analysis of patients with insomnia and comorbid anxious depression derived from 2 trials, 8 weeks of eszopiclone therapy coadministered with an SSRI resulted in significantly greater improvements in insomnia, significantly greater reductions in HDRS-17 total score, and significantly greater HDRS-17 response rates compared with placebo coadministration. There were no significant differences in response rates (when insomnia items were excluded) and remission rates, as well as in anxiety/somatization scores. Further research is warranted to determine whether these modest antidepressant effects can be replicated, and anxiolytic effects demonstrated, when evaluated in a prospective manner.

Topics: Adult; Anxiety; Azabicyclo Compounds; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Eszopiclone; Female; Fluoxetine; Humans; Hypnotics and Sedatives; Male; Piperazines; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Sleep Initiation and Maintenance Disorders; Treatment Outcome

The development of novel strategies for the treatment of posttraumatic stress disorder (PTSD) represents a critical public health need. We present the first prospective, randomized, double-blind, placebo-controlled trial of a non-benzodiazepine hypnotic agent for the treatment of PTSD and associated insomnia.. Twenty-four patients with PTSD by DSM-IV criteria and sleep disturbance were treated in a randomized, double-blind, placebo-controlled crossover study of 3 weeks of eszopiclone 3 mg at bedtime compared to placebo. The primary outcome measures were changes in scores on the Short PTSD Rating Interview (SPRINT) and the Pittsburgh Sleep Quality Index (PSQI). The data were collected from April 2006 to June 2008.. Three weeks of eszopiclone pharmacotherapy was associated with significantly greater improvement than placebo on PTSD symptom measures including the SPRINT (P = .032) and the Clinician-Administered PTSD Scale (P = .003), as well as on measures of sleep including the PSQI (P = .011) and sleep latency (P = .044). Greater improvement with eszopiclone on PTSD measures was present even when specific sleep-related items were excluded. Adverse events were consistent with the known profile of the drug.. This study provides initial evidence that pharmacotherapy with eszopiclone may be associated with short-term improvement in overall PTSD severity as well as associated sleep disturbance. Longer, more definitive study of eszopiclone in PTSD is warranted.. clinicaltrials.gov Identifier: NCT00120250.

Topics: Adult; Ambulatory Care; Azabicyclo Compounds; Comorbidity; Cross-Over Studies; Double-Blind Method; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Personality Assessment; Piperazines; Prospective Studies; Psychometrics; Sleep Initiation and Maintenance Disorders; Stress Disorders, Post-Traumatic; Young Adult

Our prior work has shown that there is improvement in self-reported sleep in persons receiving placebo in hypnotic clinical trials. We examined the components of the "placebo response" in a hypnotic clinical trial.. This was an exploratory analysis of a randomized, double-blind clinical trial of eszopiclone versus placebo in the treatment of persons with depression and insomnia who were also receiving fluoxetine at a clinic of a teaching hospital. Sixty adults with both depression and insomnia symptoms, who were free of significant primary sleep disorders, received open-label fluoxetine for 9weeks. Patients were further randomized 1:1 to receive either masked eszopiclone 3mg or placebo at bedtime after the first week of fluoxetine. We examined the respective contributions of three factors associated with the "placebo effect": (1) regression to the mean, (2) expectancy, and (3) social desirability.. There was evidence for regression to the mean for the continuous measurement of the Insomnia Severity Index (ISI) and the Hamilton Depression Rating Scale. There was evidence for expectancy in self-reported Wake After Sleep Onset, continuous measurement of ISI, and dichotomous remission/non-remitter measurement of ISI. There was evidence of social desirability affecting self-reported Total Sleep Time.. Factors that have been associated with the "placebo effect" are operating in hypnotic clinical trials. However, the role of each factor differs depending upon which self-reported variable is being considered. The findings have implications for clinical trial design in insomnia.

Topics: Adult; Antidepressive Agents, Second-Generation; Azabicyclo Compounds; Depressive Disorder; Drug Therapy, Combination; Eszopiclone; Female; Fluoxetine; Humans; Hypnotics and Sedatives; Male; Middle Aged; Piperazines; Placebo Effect; Psychiatric Status Rating Scales; Severity of Illness Index; Sleep; Sleep Initiation and Maintenance Disorders; Wakefulness

Menopause-associated insomnia is commonly associated with other symptoms (hot flashes, depression, anxiety). Given frequent symptom cooccurrence, therapies targeting sleep may provide an important approach to treatment during midlife.. Peri/postmenopausal women (40-65 years old) with sleep-onset and/or sleep-maintenance insomnia cooccurring with hot flashes and depressive and/or anxiety symptoms were randomized to eszopiclone 3 mg orally or placebo in a double-blinded, crossover 11 week trial. Changes in the Insomnia Severity Index (ISI) scale and secondary outcomes (diary-based sleep parameters, depression/anxiety, hot flashes, quality of life) were analyzed using repeated-measure linear models.. Of 59 women, 46 (78%) completed the study. Eszopiclone reduced ISI scores by 8.7 + or - 1.4 more points than placebo (P < .0001). Eszopiclone improved (P < .05) all sleep parameters, depressive symptoms, anxiety symptoms, quality of life, and nighttime but not daytime hot flashes.. Eszopiclone treats insomnia and cooccurring menopause-related symptoms. Our results provide evidence that hypnotic therapies may improve multiple domains of well-being during midlife.

Topics: Adult; Aged; Anxiety; Azabicyclo Compounds; Cross-Over Studies; Depression; Double-Blind Method; Eszopiclone; Female; Hot Flashes; Humans; Hypnotics and Sedatives; Middle Aged; Perimenopause; Piperazines; Postmenopause; Quality of Life; Sleep Initiation and Maintenance Disorders

Longer-term pharmacologic studies for insomnia in older individuals are sparse.. To evaluate the efficacy and safety of 12 weeks of nightly eszopiclone in elderly outpatients with insomnia.. Participants (65-85 years) met DSM-IV-TR criteria for insomnia with total sleep times (TST) < or = 6 h, and wake time after sleep onset (WASO) > or = 45 min. Participants were randomized to 12 weeks of eszopiclone 2 mg (n = 194) or placebo (n = 194), followed by a 2-week single-blind placebo run-out. Subject-reported measures of sleep (sTST, sleep latency [sSL], sWASO) and daytime function (alertness, concentration, wellbeing, ability to function) were assessed. AEs were monitored.. Subjects treated with 2 mg eszopiclone slept longer at night on average and at every individual time point compared to baseline than placebo subjects, as measured by TST over the 12-week double-blind period (P < 0.0001). Mean sTST over the double-blind period for eszopiclone-treated subjects was 360.08 min compared to 297.86 min at baseline, a mean change of 63.24 min. Over the double-blind period, eszopiclone-treated subjects also experienced a significantly greater improvement in sSL compared to placebo, with a mean decrease of 24.62 min versus a mean decrease of 19.92 min, respectively (P = 0.0014). Eszopiclone subjects also experienced a significantly greater decrease in WASO (mean decrease of 36.4 min) compared to placebo subjects (decrease of 14.8 min) (P < 0.0001). Post-discontinuation, sleep parameters were statistically improved versus baseline for eszopiclone (P-values < or = 0.01), indicating no rebound. The most common AEs (> or = 5%) were headache (eszopiclone 13.9%, placebo 12.4%), unpleasant taste (12.4%, 1.5%), and nasopharyngitis (5.7%, 6.2%).. In this Phase IV trial of older adults with insomnia, eszopiclone significantly improved patient-reported sleep and daytime function relative to placebo. Improvements occurred within the first week and were maintained for 3 months, with no evidence of rebound insomnia following discontinuation. The 12 weeks of treatment were well tolerated.. A Long-Term Safety and Efficacy Study of Eszopiclone in Elderly Subjects With Primary Chronic Insomnia; Registration #NCT00386334; URL - http://www.clinicaltrials.gov/ct2/show/NCT00386334?term=eszopiclone&rank=24

Topics: Adverse Drug Reaction Reporting Systems; Age Factors; Aged; Aged, 80 and over; Azabicyclo Compounds; Double-Blind Method; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Patient Satisfaction; Piperazines; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Wakefulness

Insomnia has been linked to suicidal ideas and suicide death in cross-sectional and longitudinal population-based studies. A link between insomnia and suicide has not been previously examined in the setting of a clinical trial. Herein we describe the relationship between insomnia and suicidal thinking during the course of a clinical trial for depression with insomnia.. Sixty patients aged 41.5±12.5 years (2/3 women) with major depressive episode and symptoms of insomnia received open-label fluoxetine for 9 weeks and also received blinded, randomized eszopiclone 3mg or placebo at bedtime after the first week of fluoxetine. Insomnia symptoms were assessed with the Insomnia Severity Index (ISI), and suicidal ideation was assessed with The Scale for Suicide Ideation (SSI). Depression symptoms were assessed with the depressed mood item and the anhedonia item from the Hamilton Rating Scale for Depression-24 (HRSD24), as well as a sum score for all non-sleep and non-suicide items from the HRSD (HRSD20). Measurements were taken at baseline and weeks 1, 2, 4, 6, and 8. SSI was examined by generalized linear mixed models for repeated measures as the outcome of interest for all 60 participants with ISI and various mood symptoms as independent variables, with adjustment for age, gender, treatment assignment, and baseline SSI.. Higher levels of insomnia corresponded to significantly greater intensity of suicidal thinking (p<0.01). The depressed mood item of the HRSD, and the sum of the HRSD20, both corresponded to greater suicidal thinking (p<0.001). The anhedonia item did not correspond with suicidal thinking. When both ISI and the depressed mood item, or ISI and the anhedonia item, were included together in the same model, the ISI remained an independent predictor of suicidal thinking.. The results support the concept that insomnia may be a useful indicator for suicidal ideation and now extend this idea into clinical trials. Insomnia remains an independent indicator of suicidal ideation, even taking into account the core symptoms of depression such as depressed mood and anhedonia. The complaint of insomnia during a depression clinical trial might indicate that more direct questioning about suicide is warranted.

Topics: Adolescent; Adult; Aged; Antidepressive Agents, Second-Generation; Azabicyclo Compounds; Depressive Disorder, Major; Double-Blind Method; Eszopiclone; Female; Fluoxetine; Humans; Hypnotics and Sedatives; Male; Middle Aged; Piperazines; Psychiatric Status Rating Scales; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Suicidal Ideation; Young Adult

Parkinson's disease (PD) is a common neurodegenerative disease affecting up to 1 million individuals in the United States. Sleep disturbances, typically in sleep maintenance, are found in up to 88% of these individuals and are associated with a variety of poor outcomes. Despite being common and important, there are few data to guide clinical care. We conducted a 6-week, randomized, controlled trial of eszopiclone and placebo in 30 patients with PD and insomnia. Patients with other primary sleep disorders (PSG defined) were excluded. The primary outcome was total sleep time (TST), and secondary measures included wake after sleep onset (WASO), number of awakenings, and quality of sleep, among others. The groups did not significantly differ on TST, but significant differences, favoring eszopiclone, did emerge in number of awakenings (P = 0.035), quality of sleep (P = 0.018), and in physician-rated CGI improvement (P = 0.035). There was also a trend toward significance in WASO (P = 0.071). There were no significant differences between groups in measures of daytime functioning. The drug was well tolerated, with 33% of patients on eszopiclone and 27% of patients on placebo reporting adverse events. Although modest in size, this is the first controlled study of the treatment of insomnia in patients with PD. Eszopiclone did not increase TST significantly but was superior to placebo in improving quality of sleep and some measures of sleep maintenance, which is the most common sleep difficulty experienced by patients with PD. Definitive trials of the treatment of sleep disorders in this population are warranted.

Topics: Adult; Aged; Aged, 80 and over; Azabicyclo Compounds; Double-Blind Method; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Parkinson Disease; Piperazines; Sleep Initiation and Maintenance Disorders; Time Factors; Treatment Outcome

Insomnia is associated with poor health related quality of life (HRQOL) in depressed patients. Prior clinical trials of hypnotic treatment of insomnia in depressed patients have shown improvement in HRQOL, but in these studies HRQOL was relegated to a secondary outcome, and objective measures of sleep were not undertaken.. Double-blind, randomized, placebo-controlled clinical trial.. Outpatient clinic and sleep laboratory.. 60 depressed, insomniac outpatients.. One week of open-label fluoxetine (FLX), followed by 8 more weeks of FLX combined with either eszopiclone (ESZ) 3 mg or placebo at bedtime.. The primary HRQOL measure was the daily living and role functioning subscale (DLRF) of the Basis-32. Other measures included the Q-LES-Q, self-reported sleep, PSG, actigraphy, depression severity (HRSD).. At the end of randomized treatment, patients receiving ESZ had lower (better) DLRF scores (0.81 +/- 0.64) than those receiving placebo (1.2 +/- 0.72), p = 0.01. The effect size for DLRF was 0.62, indicating a moderate effect. An advantage for ESZ was also seen in other measures of HRQOL, and most assessments of antidepressant efficacy and sleep. Women reported better end of treatment HRQOL scores than men.. ESZ treatment of insomnia in depressed patients is associated with multiple favorable outcomes, including superior improvement in HRQOL, depression severity, and sleep.

Topics: Activities of Daily Living; Affect; Antidepressive Agents, Second-Generation; Azabicyclo Compounds; Depressive Disorder, Major; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Eszopiclone; Female; Fluoxetine; Humans; Hypnotics and Sedatives; Male; Patient Satisfaction; Personality Inventory; Piperazines; Quality of Life; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome

To evaluate the polysomnographic efficacy and the safety of a range of doses of eszopiclone relative to placebo in patients with primary insomnia. Zolpidem 10 mg was included as an active control.. This multicenter, randomized, crossover study enrolled patients aged 21-64 years meeting the DSM-IV criteria for primary insomnia (n = 65). Patients received 2 nights treatment each with placebo, eszopiclone 1 mg, 2 mg, 2.5 mg, or 3 mg, and zolpidem 10 mg after randomization to one of 6 treatment sequences. Visits were separated by a 3-7 day washout. Objective efficacy was assessed by polysomnography (PSG). The primary endpoint was latency to persistent sleep (LPS); key secondary endpoints were sleep efficiency (SE) and wake time after sleep onset (WASO); other endpoints included wake time during sleep (WTDS) and number of awakenings (NAW), as well as patient-reported variables.. LPS and SE were significantly different than placebo for all active treatments (p < 0.05 for all). Significant differences from placebo were noted in the 3 objective sleep maintenance measures (WASO, WTDS, and NAW) for eszopiclone 3 mg (p < 0.05), which was not the case for zolpidem 10 mg or the other eszopiclone doses. The incidence of central nervous system adverse events was 23.4% for zolpidem 10 mg, 6.2% to 12.5% for the eszopiclone doses, and 7.9% for placebo.. Relative to placebo, all active treatments were effective in reducing LPS and increasing SE. Eszopiclone 3 mg was significantly different from placebo on the 3 PSG measures of sleep maintenance (WASO, WTDS, and NAW). Significant differences between zolpidem 10 mg and eszopiclone (2 mg or 3 mg) were not observed for PSG-measured outcomes, although the study was not powered to detect differences between the active drug conditions.

Topics: Adult; Azabicyclo Compounds; Cross-Over Studies; Diagnostic and Statistical Manual of Mental Disorders; Drug Administration Schedule; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Piperazines; Polysomnography; Pyridines; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Wakefulness; Zolpidem

To evaluate next-day driving ability, as assessed by brake reaction time (BRT), and cognitive/psychomotor function following nighttime administration of 3 mg eszopiclone.. Two randomized, double-blind, placebo-controlled, cross-over studies were performed in healthy volunteers (n = 32) and patients with primary insomnia (n = 32). Study participants received nighttime dosing of 3 mg eszopiclone or placebo. BRT and a psychometric test battery were used to assess the next-day effects of eszopiclone treatment.. In both studies, driving ability and measures of cognitive and psychomotor function were not impaired the morning after eszopiclone, as compared to placebo. All eszopiclone subjects reported improved ease in getting to sleep and quality of sleep with no significant changes in behavior upon awakening. A significant increase in next-day feelings of sedation was reported in healthy volunteers, but not in patients with primary insomnia, following eszopiclone treatment relative to placebo. Sleep induction, maintenance, duration, and efficiency, as assessed by PSG, were significantly improved following eszopiclone treatment in patients with insomnia.. Nighttime administration of 3 mg eszopiclone improved objective and subjective sleep measures in patients with insomnia (and subjective sleep measures in healthy patients) and did not impair next-day driving-related skills or measures of cognition in either study population relative to placebo.

Topics: Adult; Automobile Driving; Azabicyclo Compounds; Cognition; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Piperazines; Psychomotor Performance; Reaction Time; Sleep Initiation and Maintenance Disorders

Insomnia and generalized anxiety disorder (GAD) are prevalent disorders that may coexist.. To determine the efficacy of eszopiclone combined with escitalopram oxalate in treating insomnia comorbid with GAD.. Double-blind, randomized, placebo-controlled, parallel-group, add-on therapy 10-week study.. Multicenter outpatient study from July 2005 to April 2006.. Adults aged 18 to 64 years meeting DSM-IV-TR criteria for GAD and insomnia.. Patients received 10 mg of escitalopram oxolate for 10 weeks and were randomized to also receive either 3 mg of eszopiclone (n = 294) or placebo (n = 301) nightly for 8 weeks. For the last 2 weeks, eszopiclone was replaced with a single-blind placebo.. Sleep, daytime functioning, psychiatric measures, and adverse events.. Compared with treatment with placebo and escitalopram, treatment with eszopiclone and escitalopram resulted in significantly improved sleep and daytime functioning (P < .05), with no evidence of tolerance. Patients taking eszopiclone and escitalopram had greater improvements in total Hamilton Anxiety Scale (HAM-A) scores at each week (P < .05) and at weeks 4 through 10 with the insomnia item removed. Clinical Global Impressions (CGI) of Improvement scores were improved with eszopiclone and escitalopram at every point (P < .02), while CGI of Severity of Illness scores were not significantly different after week 1. The HAM-A response (63% vs 49%, respectively, P = .001) and remission (42% vs 36%, respectively, P = .09) rates at week 8 were higher in patients treated with eszopiclone and escitalopram than those treated with placebo and escitalopram, and median time to onset of anxiolytic response was significantly reduced (P < or = .05). After eszopiclone discontinuation, there was no evidence of rebound insomnia, and while treatment differences in anxiety measures were maintained, differences in sleep outcomes were not. Overall adverse event rates were 77.6% with cotherapy and 67.9% with monotherapy. The most common adverse events with cotherapy were unpleasant taste, headache, dry mouth, and somnolence.. Coadministration of eszopiclone and escitalopram was well tolerated and associated with significantly improved sleep, daytime functioning, anxiety, and mood in patients with insomnia and GAD.. clinicaltrials.gov Identifier: NCT00235508.

Topics: Adolescent; Adult; Anxiety Disorders; Azabicyclo Compounds; Citalopram; Comorbidity; Diagnostic and Statistical Manual of Mental Disorders; Drug Therapy, Combination; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Piperazines; Selective Serotonin Reuptake Inhibitors; Single-Blind Method; Sleep Initiation and Maintenance Disorders

The use of anticholinergic drugs in the elderly may lead to negative events such as falls, delirium, urinary retention and cognitive decline, and the higher the number of anticholinergic drugs use, the more such negative events occur. This study aims to analyze the risk factors associated with the prescription of total anticholinergic drugs in elderly outpatients and evaluate the rationality of anticholinergic drugs, and to provide a reference for reducing the adverse effects of anticholinergic drugs.. A list of drugs with anticholinergic activity based on the Beers criteria was established. The basic information (such as age and gender), clinical diagnosis, and medications of elderly outpatient were extracted from hospital electronic medical records, and the Anticholinergic Cognitive Burden (ACB) Scale was used to calculate the anticholinergic burden for each patient. Logistic regression analysis was used to identify the potential risk factors for the occurrence of problems such as multiple medication and insomnia.. A total of 1 840 prescriptions for elderly patients were reviewed. Of these patients, ACB score was more than or equal to 1 in 648 (35.22%) patients. Number of prescription medication (95% CI: 1.221 to 1.336) and insomnia (95% CI: 3.538 to 6.089) were independent factors affecting ACB scores (both P<0.01). Medications for patients of ACB scores were most commonly treated with the central nervous system drugs (such as alprazolam and eszopiclone) and for the cardiovascular system drugs (such as metoprolol and nifedipine).. There is a high rate of ACB drugs use in geriatric patients, and the clinical focus should be on multiple medication prescriptions, especially on the central nervous system drugs (such as alprazolam and eszopiclone) and cardiovascular system drugs (such as metoprolol and nifedipine). The prescription review should be emphasized to reduce adverse reactions to anticholinergic drugs in elderly patients.

Topics: Aged; Alprazolam; Cholinergic Antagonists; Eszopiclone; Humans; Metoprolol; Nifedipine; Outpatients; Risk Factors; Sleep Initiation and Maintenance Disorders

Disturbed sleep can cause to m health problems such as cognitive impairment, depressed mood, and negative effects on cardiovascular, endocrine, and immune function. This study formulates and optimizes Eszopiclone trilaminate fast dissolving film.. Prepared Eszopiclone trilaminate fast dissolving film (Eszopiclone TFDF) was characterized by disintegration time, drug release, tensile strength (TS), percentage elongation (EB%), folding endurance, taste masking test, and in vitro dissolution test. The selected formulas were F2 (0.5% xanthan gum, 10% propylene glycol), F4 (3% sodium alginate, 10% propylene glycol) and F6 (1.5% pullulan, 10% propylene glycol) were subjected to in vivo study compared to conventional Lunesta® tablet.. The results indicated that disintegration time was in the range of 940 m. Drug release was found to be in the field of 78.51%-99.99%, while TS values and EB% differed from 11.12 to 25.74 (MPa) and 25.38%-36.43%, respectively. The folding endurance went between 200 and 300 times. All formulas exhibited acceptable uniformity content, surface pH, film thickness, and a good taste feeling.. F4 had the highest Cmax (39.741 ± 6.785-μg/l) and lower Tmax (1.063 hr) among other formulas and conventional tablets. Therefore, FDFs' technology could increase the therapeutic effect of Eszopiclone.

Topics: Biological Availability; Eszopiclone; Humans; Propylene Glycols; Research Subjects; Sleep Initiation and Maintenance Disorders; Solubility; Tablets

Although long-term use of benzodiazepines and benzodiazepine receptor agonists (BZDs) has been associated with an increased risk of dependence, the incidence, details of clinical manifestations, and triggering factors of withdrawal symptoms associated with long-term BZD use at common clinical doses remain unclear.. In a multicenter, open-label study of 123 Japanese patients with insomnia, patients were given a common clinical dose of eszopiclone (2 mg) for 24 weeks, and then treatment was abruptly discontinued. Withdrawal symptoms were evaluated using the Benzodiazepine Hypnotics Withdrawal Symptom Scale (BHWSS). The Insomnia Severity Index (ISI) was used to rate insomnia severity during treatment and 2 weeks after discontinuation. Dependence and poor compliance during treatment without strict medication controls were evaluated with the Benzodiazepine Dependence Self Report Questionnaire short version (Bendep-SRQ SV) subscale sum scores for problematic use, preoccupation, and lack of compliance. Associations between the presence of clinically relevant withdrawal symptoms (BHWSS≥7) and demographic measures, ISI scores at Week 24, and Bendep-SRQ SV subscale sum scores were evaluated by multivariable stepwise logistic regression analyses.. Seventy-six patients completed treatment and 2 weeks of withdrawal; eight (10.5%) had clinically relevant withdrawal symptoms. On multiple logistic regression analysis, Bendep-SRQ SV subscale sum scores were correlated with withdrawal symptoms (odds ratio, 1.650; 95% confidence interval, 1.105-2.464; p = 0.014). Exacerbation of post-discontinuation insomnia was not significantly different between patients who showed clinically relevant withdrawal symptoms and those who did not (p = 0.245).. Dependence and poor compliance may contribute to withdrawal symptoms with long-term BZD use. Providing guidance to ensure proper compliance is thought to be the best way to mitigate withdrawal symptoms.. UMIN000024462 (18/10/2016).

Topics: Benzodiazepines; Eszopiclone; Humans; Hypnotics and Sedatives; Prevalence; Prospective Studies; Sleep Initiation and Maintenance Disorders; Substance Withdrawal Syndrome

To reduce the number of falls caused by hypnotic agents, the standardization of insomnia treatment was carried out at Yamaguchi University Hospital from April 2019. There were concerns that medical costs would increase due to the selected medicines-suvorexant and eszopiclone-being more expensive than conventional benzodiazepines. In this study, the standardization of insomnia treatment was evaluated by pharmacoeconomics. The costs of the hypnotic agents was considered, as was the cost of examination/treatment following falls. Effectiveness was evaluated as the incidence of falls within 24 hours of taking hypnotic agents. This analysis took the public healthcare payer's perspective. Propensity score matching based on patient background, showed that, per hospitalization the medicine costs of the recommended group increased by 1,020 yen, however, the examination/treatment costs following falls decreased by 487 yen when compared with the non-recommended group. Overall, the recommended group incurred costs of 533 yen more per hospitalization for patients prescribed hypnotic agents compared to the non-recommended group, but the incidence of falls for the recommended group was significantly lower than that in the non-recommended group (1.9% vs. 6.3%; p<0.01). These results suggest that in order to prevent the incidence of falls by 1 case, it is necessary to increase costs by 12,086 yen which is the subthreshold cost for switching to the recommended medicine as standardization. The selection of recommended medicines may be a cost-effectiveness option compared with non-recommended medicines.

Topics: Accidental Falls; Aged; Aged, 80 and over; Azepines; Benzodiazepines; Cost-Benefit Analysis; Economics, Pharmaceutical; Eszopiclone; Female; Hospitalization; Humans; Hypnotics and Sedatives; Male; Middle Aged; Sleep Initiation and Maintenance Disorders; Triazoles

Topics: Acetamides; Drug Labeling; Drug-Related Side Effects and Adverse Reactions; Eszopiclone; Humans; Pyrimidines; Safety Management; Sleep Initiation and Maintenance Disorders; United States; United States Food and Drug Administration; Zolpidem

The non-benzodiazepine sedative hypnotic (NBSH) eszopiclone improves polysomnography (PSG) quality and continuous positive airway pressure (CPAP) adherence. It is unclear whether zolpidem has the same effect and neither NBSH has been studied in populations with milder forms of obstructive sleep apnea.. We performed a retrospective analysis on patients undergoing level I PSG at our institution. Patients are pre-medicated with NBSHs at the discretion of the sleep physician. We compared PSG/CPAP titration quality and subsequent CPAP adherence for patients receiving NBSHs or no pre-study medication. We adjusted for obstructive sleep apnea pre-test probability (PTP), arousal threshold, and other factors showing differences at baseline.. Data on 560 patients were analyzed. Mean age and body mass index were 42.2 ± 10.1 and 28.8 ± 4.5, respectively. Median apnea hypopnea index was 12.9 (6.4-25.3), 100 (18.0%) patients had normal studies, 97 (17.3%) were split, and 457 (81.6%) had a respiratory low-arousal threshold. After adjusting for differences at baseline, neither NBSH was associated with sleep efficiency, wake after sleep onset, or total sleep time on PSG. After adjustment, patients receiving eszopiclone had a higher apnea hypopnea index at the final CPAP pressure (β = 14.2; 95% confidence intervals (CI) 7.2-21.2; p < 0.001) and were more likely to have an unacceptable titration (odds ratio (OR) = 6.6; 95% CI 2.0-21.0; p = 0.002). When only split-night studies were examined, there were no differences in any adherence variables across or between categories.. In a population with predominantly mild obstructive sleep apnea, NBSHs did not improve PSG or CPAP titration quality and did not increase CPAP adherence. There was no difference in effect between eszopiclone and zolpidem.

Topics: Adult; Analysis of Variance; Body Mass Index; Continuous Positive Airway Pressure; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Polysomnography; Retrospective Studies; Sleep Initiation and Maintenance Disorders; Statistics, Nonparametric; Treatment Adherence and Compliance; Zolpidem

Patients transferred out of the intensive care unit (ICU) are always impaired by sleep disorders. Cognitive behavioral therapy for insomnia (CBT-I) and eszopiclone are 2 commonly prescribed strategies for insomnia. In the current study, the effect of the combined application of the 2 methods on sleep disorders in ICU transferred out patients was assessed.Twenty-nine insomnia patients receiving combined treatment of CBT-I and eszopiclone and a corresponding number of patients treated with eszopiclone were collected. The incidence of discomfort experiences in ICU was recorded. Polysomnogram (PSG), Pittsburgh Sleep Quality Index (PSQI), self-rating anxiety scale (SAS), self-rating depression scale (SDS), and treatment emergent symptom scale (TESS) were used to assess the treatment efficacy and side effects.Hospitalization for over 7 days, use of benzodiazepines, and experiencing anxiety, insomnia, and mechanical ventilation increased chances of sleep disorders. The sleep latency, awakening time, and total sleep time were further improved in patients treated with the combined therapy than patients treated with eszopiclone (t = -2.334, -2.412, 2.383, P < .05). Similar changing pattern was observed for PSQI score (t = -2.262, P < .05). The improvement effect of the combined therapy on the sleep efficacy, SWS phase III, and rapid eye movement sleep was also significantly stronger (t = 2.112, 2.268, 2.311, P < .05). Moreover, the SAS and SDS scores in patients treated with the combined therapy decreased more than those of patients treated with eszopiclone.The efficacy of CBT-I combined with eszopiclone in the treatment of sleep disorders in ICU transferred out patients was better than eszopiclone.

Topics: Adult; Cognitive Behavioral Therapy; Combined Modality Therapy; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Intensive Care Units; Male; Middle Aged; Patient Transfer; Retrospective Studies; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders; Treatment Outcome

The objective of this study was to test the hypothesis that use of zolpidem, eszopiclone, and zaleplon would be associated with increased risk of traumatic brain injury (TBI) and hip fracture.. We conducted a case-crossover study on a 5% random sample of Medicare beneficiaries age 65 y or older hospitalized with either TBI (n = 15,031) or hip fracture (n = 37,833) during 2007-2009. Use of zolpidem, eszopiclone, or zaleplon during the 30-day period prior to injury hospitalization was compared to use during four control periods at 3, 6, 9, and 12 mo prior to injury. The primary outcome was hospitalization for TBI or hip fracture.. Zolpidem use during the month prior to injury was associated with increased risk of TBI (odds ratio [OR] 1.87; 95% confidence interval [CI] 1.56, 2.25); however, eszopiclone use during the same period was not associated with increased risk (OR 0.67; 95% CI 0.40, 1.13). Zolpidem use during the month prior to injury was associated with increased risk of hip fracture (OR 1.59; 95% CI 1.41, 1.79); however, eszopiclone use during the same period was not associated with increased risk (OR 1.12; 95% CI 0.83, 1.50). Analysis of zaleplon use in the month prior to injury was limited by low drug utilization but was not associated with increased risk of TBI (OR 0.85; 95% CI 0.21, 3.34) or hip fracture (OR 0.92; 95% CI 0.40, 2.13) in this study.. For the treatment of insomnia in older adults, eszopiclone may present a safer alternative to zolpidem, in terms of fall-related injuries.

Topics: Accidental Falls; Acetamides; Aged; Aged, 80 and over; Brain Injuries, Traumatic; Cross-Over Studies; Eszopiclone; Female; Hip Fractures; Hospitalization; Humans; Hypnotics and Sedatives; Male; Odds Ratio; Pyridines; Pyrimidines; Risk Assessment; Sleep Initiation and Maintenance Disorders; Zolpidem

Topics: Adult; Bipolar Disorder; Eszopiclone; Female; Hallucinations; Humans; Hypnotics and Sedatives; Sleep Initiation and Maintenance Disorders; Visual Perception

Our patient presented with repetitive, self-limited bouts of forceful hiccups in sleep. Eszopiclone, a commonly prescribed hypnotic, appeared to cause these intermittent hiccups. This case is a reminder that eszopiclone may cause this adverse effect, and that it may be the bed partner and not the patient who furnishes critical sleep medicine history.

Topics: Azabicyclo Compounds; Eszopiclone; Female; Hiccup; Humans; Hypnotics and Sedatives; Middle Aged; Piperazines; Sleep Initiation and Maintenance Disorders

Topics: Azabicyclo Compounds; Dose-Response Relationship, Drug; Eszopiclone; Female; GABA-A Receptor Agonists; Humans; Hypnotics and Sedatives; Male; Piperazines; Sleep Initiation and Maintenance Disorders; United States; United States Food and Drug Administration

Topics: Acetamides; Azabicyclo Compounds; Controlled Clinical Trials as Topic; Double-Blind Method; Eszopiclone; Humans; Hypnotics and Sedatives; Piperazines; Pyridines; Pyrimidines; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Zolpidem

Let patients know that hot flashes, vaginal dryness, and other common menopausal symptoms can be treated successfully with hormonal and nonhormonal agents.

Topics: Acupuncture Therapy; Adjuvants, Immunologic; Administration, Cutaneous; Administration, Topical; Affect; Age Factors; Androgen Antagonists; Androgens; Antidepressive Agents; Antidepressive Agents, Second-Generation; Atrophic Vaginitis; Azabicyclo Compounds; Bupropion; Cyproterone Acetate; Dehydroepiandrosterone; Dose-Response Relationship, Drug; Dyspareunia; Estrogens; Eszopiclone; Exercise; Female; Hair; Hormone Replacement Therapy; Hot Flashes; Humans; Hypnotics and Sedatives; Libido; Life Style; Lubricants; Menopause; Middle Aged; Mineralocorticoid Receptor Antagonists; Minoxidil; Phytotherapy; Piperazines; Sleep Initiation and Maintenance Disorders; Spironolactone; Testosterone

Eszopiclone is the active S-enantiomer of R,S-zopiclone, and is a cyclopyrrolone hypnotic acting via the GABA-benzodiazepine receptor system. Nearly 6 million prescriptions for eszopiclone are written yearly in the United States.. This paper addresses the pharmacokinetic properties of eszopiclone and the extent to which the longer half-life of eszopiclone compared to other commonly used hypnotics (immediate-release zolpidem, modified-release zolpidem, triazolam, zaleplon) may translate into either improved efficacy in enhancing sleep maintenance, or increased probability of residual sedative or performance-impairing effects.. Eszopiclone is metabolized mainly by Cytochrome P450-3A (CYP3A) isoforms. The mean half-life in healthy nonelderly individuals (6.1 h) is prolonged in the elderly, in patients with hepatic insufficiency, and by coadministration of CYP3A inhibitors. In clinical trials, eszopiclone consistently improves sleep maintenance relative to placebo, based on measures of shortened wake time after sleep onset, and prolonged total sleep time. However eszopiclone may also produce residual sedation and impairment of driving performance in the initial morning waking hours. A bitter or metallic taste is a common though non-serious adverse effect of eszopiclone. Overall, eszopiclone provides a therapeutic option for patients with sleep maintenance problems, though with accompanying potential for residual morning sedation, as well as a relatively high dollar cost of treatment.

Topics: Acetamides; Adult; Aged; Azabicyclo Compounds; Clinical Trials as Topic; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Eszopiclone; Half-Life; Hepatic Insufficiency; Humans; Hypnotics and Sedatives; Piperazines; Pyridines; Pyrimidines; Receptors, GABA-A; Sleep; Sleep Initiation and Maintenance Disorders; Triazolam; United States; Zolpidem

Insomnia in patients with bipolar disorder (BD) can cause distress, daytime dysfunction, cognitive impairment, worsening of hypomanic/manic symptoms and increased suicide risk. Physicians often prescribe hypnotics for BD patients with insomnia although no hypnotic has a specific FDA indication for this use. In this study, the patterns of use, efficacy and safety of five nonbenzodiazepine hypnotics (NBZHs) were assessed in a large group of outpatients with BD.. A chart review was performed for all older adolescents and adult BD outpatients in a private outpatient clinic. Clinical data was collected for any patient who had ever been prescribed a NBZH for insomnia and included successful current use, past unsuccessful treatments, side effects, duration of use, concurrent psychiatric medications, and absence or presence of untoward events often associated with chronic use of hypnotics.. A significant number of BD patients take NBZHs as needed or on a daily basis. Four NBZHs had adequate success rates; ramelteon was limited in efficacy. Some patients experienced satisfactory results from a NBZH after unsuccessful trials with one or more other NBZHs. About half of the current NBZH users are taking them on a daily long-term basis, and none of these patients have experienced unacceptable untoward events. About three quarters of the chronic NBZH users are taking antimanic medications concurrently, and less than half of the chronic users are taking antidepressants.. The results may not be generalizable to other BD populations. A control group was not included in the design. Chronic users of NBZHs were not asked to discontinue their NBZH in order to confirm indication for long-term use.. Most NBZHs can be effective and safe agents for selected BD outpatients with episodic or chronic insomnia. Failure to respond to one or more NBZH does not preclude a satisfactory response to a different NBZH. Some BD patients who take maintenance antimanic agents also require NBZH treatment. Overactivation from antidepressant treatment does not contribute to chronic NBZH use in most BD patients.

Topics: Acetamides; Adolescent; Adult; Azabicyclo Compounds; Bipolar Disorder; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Indenes; Male; Piperazines; Pyridines; Pyrimidines; Retrospective Studies; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Zolpidem

To summarize the signalment, clinical signs observed, time to onset of clinical signs, duration of clinical signs, and the outcome in a large case series of nonbenzodiazepine sleep aid ingestions in dogs, including 2 sleep aids that have not been previously described in the veterinary literature.. Retrospective study conducted between 2004 and 2010.. An animal poison control center based out of Bloomington, MN.. During this time frame, 453 cases were identified involving 467 dogs. Of these cases, 150 cases were excluded due to incomplete medical records, multipet households, or the inability to calculate a dose exposure. A total of 317 dogs with presumed sleep aid medication toxicosis were included.. None.. Records of dogs with sleep aid medication toxicosis identified by a review of an animal poison control center electronic database were evaluated. The most common sleep aid medications ingested were zolpidem (240/317 [75.7%]), eszopiclone (62/317 [19.5%]), and zaleplon (15/317 [4.7%]). Overall, clinical signs developed in 36% of patients (115/317), while 64% (202/317) remained asymptomatic. The most common organ systems affected and clinical signs seen involved the central nervous system (eg, agitation, sedation) and gastrointestinal tract (eg, anorexia, hypersalivation, vomiting).. Overall, the prognosis for dogs with sleep aid medication toxicosis was excellent, and no fatalities were reported in this clinical population. As significant clinical signs can still be seen with ingestion, appropriate decontamination is warranted in asymptomatic patients via emesis or gastric lavage, followed by activated charcoal administration. Symptomatic patients should be hospitalized for monitoring and supportive care for a minimum of 12 hours or until clinical signs resolve.

Topics: Acetamides; Animals; Azabicyclo Compounds; Benzodiazepines; Comorbidity; Dog Diseases; Dogs; Eszopiclone; Female; Hypnotics and Sedatives; Male; Piperazines; Poison Control Centers; Prognosis; Pyridines; Pyrimidines; Retrospective Studies; Sleep Initiation and Maintenance Disorders; Zolpidem

To assess the cost-effectiveness of treatment with eszopiclone for chronic primary insomnia in adults.. A model using patient-level data from a 6-month, double-blind, placebo-controlled, clinical trial (n = 824), combined with data from a claims database and published literature, was used to assess the quality-adjusted life years (QALYs) gained and costs associated with eszopiclone versus placebo in adults with primary insomnia. Quality of life data were collected during the trial via the SF-36, from which preference-based utility scores were derived using published algorithms. Medical and absenteeism costs, estimated via a retrospective analysis of a claims and absenteeism database, were assigned to patients based on the degree of severity of their insomnia, assessed via the Insomnia Severity Index collected in the clinical trial. Presenteeism costs (lost productivity while at work) were estimated from responses to the Work Limitation Questionnaire collected during the trial. Six-month gains in QALYs and costs for each treatment group were calculated to derive cost-effectiveness ratios. Uncertainty was addressed via univariate and multivariate sensitivity analyses.. Over the 6-month period, eszopiclone use resulted in a net gain of 0.0137 QALYs over placebo at an additional cost of $67, resulting in an incremental cost per QALY gained of slightly less than $5,000. When absenteeism and presenteeism costs were excluded, the cost-effectiveness ratio increased to approximately $33,000 per QALY gained, which is below the commonly used threshold of $50,000 used to define cost-effectiveness. Extensive sensitivity analyses indicate the results are generally robust.. Our model, based on efficacy data from a clinical trial, demonstrated eszopiclone was cost-effective for the treatment of primary insomnia in adults, especially when lost productivity costs were included.

Topics: Absenteeism; Adult; Azabicyclo Compounds; Controlled Clinical Trials as Topic; Cost-Benefit Analysis; Double-Blind Method; Drug Costs; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Models, Economic; Piperazines; Quality-Adjusted Life Years; Referral and Consultation; Sleep Initiation and Maintenance Disorders; United States; Utilization Review; Young Adult

RP 48497 is a photodegradation product of eszopiclone, a non-benzodiazepine sedative-hypnotic used in the treatment of insomnia. We report herein the first synthesis of RP 48497 via reduction, chlorination, and recyclization of 6-(5-chloropyridin-2-yl)-7-hydroxy-6,7-dihydropyrrolo[3,4-b]pyrazin-5-one (3), a key intermediate in the synthesis of eszopiclone. The structure of RP 48497 was confirmed by its (1)H-NMR and MS data. The mechanism of the reduction step in the synthesis of RP 48497 was also studied and the key parameters were determined. These findings should be important for quality control purposes in the manufacture of eszopiclone.

Topics: Azabicyclo Compounds; Chlorine; Cyclization; Eszopiclone; Hypnotics and Sedatives; Molecular Structure; Oxidation-Reduction; Piperazines; Pyrazines; Sleep Initiation and Maintenance Disorders

Topics: Acetamides; Animals; Azabicyclo Compounds; Carcinoma, Basal Cell; Eszopiclone; Humans; Indenes; Piperazines; Pyrimidines; Randomized Controlled Trials as Topic; Skin Neoplasms; Sleep Initiation and Maintenance Disorders; United States; United States Food and Drug Administration

Fifteen epidemiologic studies have associated hypnotic drugs with excess mortality, especially excess cancer deaths. Until recently, insufficient controlled trials were available to demonstrate whether hypnotics actually cause any cancers. The US Food and Drug Administration (FDA) Approval History and Documents were accessed for zaleplon, eszopiclone and ramelteon. Since zolpidem was used as a comparison drug in zaleplon trials, some zolpidem data were also available. Incident cancers occurring during randomized hypnotics administration or placebo administration were tabulated. Combining controlled trials for the four drugs, there were 6190 participants given hypnotics and 2535 given placebo in parallel. There were eight mentions of incident non-melanoma skin cancers among participants receiving hypnotics but no comparable mentions of cancers among those receiving placebo (P = 0.064, one-tailed). There were also four mentions of incident tumors of uncertain malignancy among those receiving hypnotics but none among those receiving placebo, so combining uncertain and definite malignancies yielded a more significant contrast (P = 0.016). FDA files revealed that all four of the new hypnotics were associated with cancers in rodents. Three had been shown to be clastogenic. Together with the epidemiologic data and laboratory studies, the available evidence signals that new hypnotics may increase cancer risk. Due to limitations in available data, confirmatory research is needed.

Topics: Acetamides; Animals; Azabicyclo Compounds; Carcinoma, Basal Cell; Causality; Cross-Sectional Studies; Eszopiclone; Follow-Up Studies; Humans; Hypnotics and Sedatives; Incidence; Indenes; Melanoma; Piperazines; Pyridines; Pyrimidines; Randomized Controlled Trials as Topic; Skin Neoplasms; Sleep Initiation and Maintenance Disorders; United States; United States Food and Drug Administration; Zolpidem

Topics: Azabicyclo Compounds; Drug Costs; Drug Interactions; Eszopiclone; Humans; Medical History Taking; Nurse's Role; Nursing Assessment; Patient Education as Topic; Patient Selection; Piperazines; Sleep Initiation and Maintenance Disorders

Although it has been claimed that insomnia causes an increased risk for depression, adequate controlled trials testing this hypothesis have not been available. This study contrasted the incidence of depression among subjects receiving hypnotics in randomized controlled trials versus those receiving placebo.. The incidence of depression among patients randomized to hypnotic drugs or placebo was compiled from prescribing information approved by the United States Food and Drug Administration (FDA) and from FDA New Drug Application documents. Available data for zolpidem, zaleplon, eszopiclone, and ramelteon were accessed.. Data for 5535 patients randomized to a hypnotic and for 2318 randomized to placebo were compiled. The incidence of depression was 2.0% among participants randomized to hypnotics as compared to 0.9% among those randomized in parallel to placebo (p < 0.002).. Modern hypnotics were associated with an increased incidence of depression in data released by the FDA. This suggests that when there is a risk of depression, hypnotics may be contra-indicated. Preventive treatments such as antidepressant drugs, cognitive-behavioral therapy, or bright light might be preferred. Limitations in the FDA data prevented a formal meta-analysis, and there was a lack of information about drop-out rates and definitions of depression. Trials specifically designed to detect incident depression when treating insomnia with hypnotic drugs and better summarization of adverse events in trials submitted to the FDA are both necessary.

Topics: Acetamides; Azabicyclo Compounds; Cross-Sectional Studies; Depressive Disorder, Major; Drug Prescriptions; Eszopiclone; Follow-Up Studies; Humans; Hypnotics and Sedatives; Incidence; Indenes; Long-Term Care; Odds Ratio; Piperazines; Pyridines; Pyrimidines; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; United States; United States Food and Drug Administration; Zolpidem

According to the National Institutes of Health, approximately 30 percent of all Americans complain of sleep disruption, while 10 percent display symptoms congruent with chronic insomnia. One of the most common treatments for insomnia is prescription sleep medications that help people fall asleep and remain asleep. Historically barbiturates were initially popular for treating insomnia, but their long "hangover" effect made them easily replaced with the introduction of the benzodiazepines. Triazolam (Halcion), diazepam (Valium), and oxazepam (Serax) rapidly became the treatment of choice for insomnia. Recently a new class of nonbenzodiazepines---the "z-sedatives"--has overtaken the older benzodiazepines as the most commonly prescribed sleep medications. The three most popular z-drugs are zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta). The Food and Drug Administration (FDA) also recently approved the production of zolpidem tartrate, a generic form of Ambien. Many dentists prescribe these medications for patients who have difficulty sleeping the night prior to an appointment or as a procedural sedative. With 43 million prescriptions for sleep medications filled in 2005, generating $2.7 billion for pharmaceutical companies, it is important that dentists be aware of these drugs' mechanism of action and potential drug interactions.

Topics: Acetamides; Azabicyclo Compounds; Drug Interactions; Eszopiclone; Humans; Hypnotics and Sedatives; Piperazines; Pyridines; Pyrimidines; Sleep Initiation and Maintenance Disorders; Zolpidem

Sleep and wakefulness are both active processes regulated by complex neural networks, the precise mechanisms of which are not yet fully understood. Patients with insomnia, particularly primary insomnia, often exhibit hyperarousal and may receive therapies to reduce wakefulness and promote sleep. Apart from standard sleep hygiene measures, physicians can offer patients behavioral therapy (if available) or pharmacologic therapy, or both. Both provide relief for insomnia symptoms; however, that relief appears durable on cessation of behavioral therapy only. Practice parameters for the treatment of insomnia are available for the use of behavioral therapy, but those for pharmacologic therapy are dated and do not reflect the current state of clinical practice. Hypnotic agents currently approved for use by the US Food and Drug Administration may be used for only 4 weeks and are limited by variable efficacy and concerns about safety profiles. This situation has prompted many physicians to prescribe antidepressants and other agents for their sedating properties, despite a paucity of efficacy and safety data in patients with insomnia. Of the hypnotic agents currently under clinical investigation, so far only eszopiclone has been studied in regard to efficacy over a prolonged period (6 months) with no evidence of significant tolerance. Although reports suggest that other hypnotics may also provide longer-term benefits, further research is needed to determine the optimal duration of treatment in chronic insomnia.

Topics: Antidepressive Agents; Azabicyclo Compounds; Behavior Therapy; Benzodiazepines; Eszopiclone; Histamine Antagonists; Humans; Hypnotics and Sedatives; Piperazines; Sleep Initiation and Maintenance Disorders