Effects of eszopiclone on safety, subjective measures of efficacy, and quality of life in elderly and nonelderly Japanese patients with chronic insomnia, both with and without comorbid psychiatric disorders: a 24-week, randomized, double-blind study

Abstract

Background: The primary objective of this study was to evaluate long-term (24-week) safety of eszopiclone in elderly and nonelderly Japanese patients with chronic insomnia. The secondary objectives were to evaluate short-term (4-week) efficacy and to assess for rebound insomnia or dependence after long-term treatment.

Methods: Patients (n = 164 elderly; n = 161 nonelderly), with or without psychiatric comorbidities, were randomized to receive low-dose (1 mg, elderly; 2 mg, nonelderly) or high-dose (2 mg, elderly; 3 mg, nonelderly) eszopiclone. The safety evaluation included adverse events, vital signs, clinical laboratory parameters, and electrocardiogram. Efficacy was assessed using patient reports of sleep latency (SL), total sleep time (TST), wake time after sleep onset (WASO), number of awakenings (NA), quality of sleep, depth of sleep, daytime sleepiness, daytime ability to function, and the 36-item Short Form (SF-36) Health Survey.

Results: The rate of adverse events was 81.5% in the 1-mg elderly group, 79.5% in the 2-mg elderly group, 82.1% in the 2-mg nonelderly group, and 87.0% in the 3-mg nonelderly group. Dysgeusia was the most common adverse event and was dose-related. Of 12 serious adverse events, none were considered by the investigator to be related to study medication. No rebound insomnia was observed. Eszopiclone significantly improved SL, TST, WASO, NA, and daytime sleepiness and function from baseline to Week 4, irrespective of age and psychiatric comorbidity. Improvements were also observed in SF-36 Mental Health Component scores in elderly and nonelderly patients with psychiatric comorbidities.

Conclusions: Irrespective of age, eszopiclone appeared safe as administered in this study for 24 weeks. Eszopiclone improved sleep variables in insomnia patients with and without psychiatric disorders and health-related quality of life in those with psychiatric disorders.

Trial registration: ClinicalTrials.gov #NCT00770692; http://clinicaltrials.gov/ct2/show/NCT00770692.

Figure 1

Summary of study schematic from screening through study completion. Visits 6, 7, and 8 were conducted at 4-week intervals. Adverse events were collected from Weeks 1 to 25. Sleep variables were obtained at Week −1 (baseline) and Weeks 1 to 4. SF-36 was assessed at Weeks −1, 4, 12 and 24.

Figure 2

Patient disposition.^aRandomization and the first administration of eszopiclone were performed on Day 0; ^bPatients could have more than 1 reason for study discontinuation; ^cDuring the week after discontinued intervention. n₁ = number of patients with comorbid psychiatric disorders; n₂ = number of patients without psychiatric disorders.

Figure 3

Median values for sleep latency at baseline and at Weeks 1 through 4. Median sleep latency (baseline; Week 1 through 4) were obtained in elderly patients receiving eszopiclone 1 mg (A) or 2 mg (B) and in nonelderly patients receiving eszopiclone 2 mg (C) or 3 mg (D). *P < 0.001 versus baseline for all treatment groups at all time points.

Figure 4

Median values for total sleep time at baseline and at Weeks 1 through 4. Median total sleep time (baseline; Weeks 1 through 4) were obtained in elderly patients receiving eszopiclone 1 mg (A) or 2 mg (B) and in nonelderly patients receiving eszopiclone 2 mg (C) or 3 mg (D). *P < 0.001 versus baseline for all treatment groups at all time points.

Figure 5

Median values for sleep latency at baseline, Week 24, and Week 25. Median sleep latency (baseline; Weeks 24 and 25) were obtained in elderly patients receiving eszopiclone 1 mg (A) or 2 mg (B) and in nonelderly patients receiving eszopiclone 2 mg (C) or 3 mg (D). For the patients who discontinued study treatment, data at final administration of study drug were handled as Week 24 data, and data at 1 week after final administration of study drug were handled as Week 25 data (last observation carried forward [LOCF]). *P < 0.001 versus baseline; ^†P < 0.05 versus baseline; ^‡P < 0.01 versus baseline.