eszopiclone and Depressive-Disorder--Major

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

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

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

Eszopiclone is effective for the treatment of insomnia in patients with insomnia and comorbid major depressive disorder (MDD). Both conditions impose significant economic burden, with the US societal cost of depression estimated at USD 50 billion annually.. The purpose of this analysis was to examine the costs and benefits of eszopiclone co-administered with fluoxetine (ESZ+FLX) compared to placebo co-administered with fluoxetine (PBO+FLX) in adults meeting the DSM-IV criteria for insomnia and MDD.. Data from 434 patients enrolled in an 8-week clinical trial who met the economic-subanalysis criteria were examined. The costs of medical care (in 2007 USUSD ) and lost work time were estimated from the Hamilton Depression Scale (HAM-D17) scores using published algorithms. Cost of lost productivity while at work was based on responses to the Work Limitations Questionnaire. The impact of therapy on quality-adjusted life years (QALYs) was estimated by transforming HAM-D17 (base case analysis) or Short Form Health Survey (SF-12) (scenario analyses) responses into health utility scores using published algorithms. Drug costs were estimated based on average wholesale price.. The mean 8-week increases in QALYs from baseline were 0.0392 and 0.0334 for the ESZ+FLX and PBO+FLX groups, respectively. Mean per-patient costs were USD 1,279 and USD 1,198 for the respective groups. Thus, co-treatment resulted in net increases of 0.0058 QALYs and USD 81, leading to an incremental cost per QALY gained of approximately USD 14,000.. Co-administration of eszopiclone and fluoxetine improved patients' insomnia symptoms and appeared to be a cost-effective treatment strategy for patients with insomnia and comorbid MDD. One limitation of this study is that optimal utility estimation techniques were not available. Utilities were instead derived indirectly using the HAM-D17 (disease-specific, not generic) or SF-12 (generic, but potentially insensitive to important changes in some conditions) instruments.. Sleep disturbance is predictive of depression relapse, and is the most common residual symptom in patients who have been successfully treated with fluoxetine for depression. Thus, identifying cost-effective strategies for the treatment of insomnia symptoms is important for this patient population.. Treatment guidelines and drug coverage decisions should be based on clinical evidence, effectiveness, and economic criteria (i.e., whether an effective drug therapy produces sufficient benefits given its costs). This information about the overall value of eszopiclone can be measured as the cost per QALY gained with the use of ESZ+FLX compared with FLX alone. In order to make decisions based on value, payers and policy makers must have access to reliable cost-effectiveness information.. The residual efficacy observed in the clinical trial following the discontinuation of co-therapy should be explored further to determine whether intermittent treatment with ESZ+FLX is a cost-effective strategy.

Topics: Absenteeism; Algorithms; Antidepressive Agents, Second-Generation; Azabicyclo Compounds; Cost of Illness; Cost-Benefit Analysis; Depressive Disorder, Major; Double-Blind Method; Drug Costs; Eszopiclone; Fluoxetine; Humans; Hypnotics and Sedatives; Personality Inventory; Piperazines; Psychometrics; Quality-Adjusted Life Years

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

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