eszopiclone and Chronic-Disease

Generalized anxiety disorder (GAD) has a lifetime prevalence in the US population of about 5.7%. Typically, GAD begins in early adulthood and tends to have a chronic and persistent course. The disorder frequently presents comorbidly with other conditions, and about 90% of patients with GAD have at least 1 comorbid lifetime psychiatric disorder. Patients with GAD tend to be high users of medical services; the disorder is associated with significant physical as well as psychological symptomatology and impacts health, family relationships, and employment. Pharmacologic and psychosocial treatments are available for GAD. Different side effect profiles, speed of onset of action, and discontinuation requirements of individual drugs need to be taken into account when selecting treatment. Treatment selection should include consideration of comorbidity, psychological function, social impairment, and refractoriness, as well as the need for ongoing intervention for many individuals. Innovative treatments, including anticonvulsants, atypical antipsychotics, and others, as well as treatment targeting concomitant insomnia, may help improve outcomes for affected individuals.

Topics: Anti-Anxiety Agents; Anticonvulsants; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Anxiety Disorders; Azabicyclo Compounds; Benzodiazepines; Buspirone; Chronic Disease; Citalopram; Cognitive Behavioral Therapy; Comorbidity; Diagnosis, Differential; Drug Therapy, Combination; Eszopiclone; Humans; Mental Health Services; Neurobiology; Neuroprotective Agents; Piperazines; Prevalence; Recurrence; Riluzole; Selective Serotonin Reuptake Inhibitors; United States

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

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 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 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