Nightly treatment of primary insomnia with eszopiclone for six months: effect on sleep, quality of life, and work limitations

Abstract

Study objectives: To evaluate 6 months' eszopiclone treatment upon patient-reported sleep, fatigue and sleepiness, insomnia severity, quality of life, and work limitations.

Design: Randomized, double blind, controlled clinical trial.

Setting: 54 research sites in the U.S.

Patients: 830 primary insomnia patients who reported mean nightly total sleep time (TST) < or = 6.5 hours/night and/or mean nightly sleep latency (SL) >30 min.

Intervention: Eszopiclone 3 mg or matching placebo.

Measurements: Patient-reported sleep measures, Insomnia Severity Index, Medical Outcomes Study Short-Form Health Survey (SF-36), Work Limitations Questionnaire, and other assessments measured during baseline, treatment Months 1-6, and 2 weeks following discontinuation of treatment.

Results: Patient-reported sleep and daytime function were improved more with eszopiclone than with placebo at all months (P <0.001). Eszopiclone reduced Insomnia Severity Index scores to below clinically meaningful levels for 50% of patients (vs 19% with placebo; P <0.05) at Month 6. SF-36 domains of Physical Functioning, Vitality, and Social Functioning were improved with eszopiclone vs placebo for the Month 1-6 average (P < 0.05). Similarly, improvements were observed for all domains of the Work Limitations Questionnaire with eszopiclone vs placebo for the Month 1-6 average (P <0.05).

Conclusions: This is the first placebo-controlled investigation to demonstrate that long-term nightly pharmacologic treatment of primary insomnia with any hypnotic enhanced quality of life, reduced work limitations, and reduced global insomnia severity, in addition to improving patient-reported sleep variables.

Figure 1

Flow diagram to illustrate progression of patients through the trial, based upon the Consolidated Standards of Reporting Trials (CONSORT) statement. See Altman DG, Schulz KF, Moher D. et al. The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med 2001; 134: 663–694.

Figure 2

Median values for key hypnotic efficacy measures at baseline and during months 1–6 of double-blind treatment for eszopiclone (solid lines) and placebo (dashed lines) groups. Panel A: sleep latency. Panel B: wake after sleep onset; Panel C: total sleep time; *Change from baseline P-value vs placebo <0.0001.

Figure 3

Insomnia Severity Index (ISI) scores at Baseline, Month 6 and End of Study (after the 2-week placebo run-out period). Overall P-values between treatment groups: Baseline P = 0.34; Month 6, P <0.001; and End of Study P = 0.005. *P-value vs placebo <0.05. ISI total score 0–7 = Insomnia not clinically significant (NCS), 8–14 = subthreshold insomnia, 15–21 = moderate insomnia and 22–28 = severe insomnia.

Figure 4

Mean scores for the 5 Work Limitations Questionnaire averaged across Months 1–6. Placebo group = gray bars; eszopiclone group= black bars. Error bars indicate standard deviation of the mean.

Figure 5

Median values for key hypnotic efficacy measures at baseline, month 6, and each night during the discontinuation period for eszopiclone (solid lines) and placebo (dashed lines) groups. Panel A: sleep latency; Panel B: wake after sleep onset; Panel C: total sleep time. Both placebo and eszopiclone groups remained significantly improved from baseline (P <0.001) during the discontinuation period. *P <0.05 vs placebo