Elsevier

Sleep Medicine

Volume 12, Issue 9, October 2011, Pages 920-923
Sleep Medicine

Brief Communication
Use of a post-sleep questionnaire-interactive voice response system (PSQ-IVRS) to evaluate the subjective sleep effects of ramelteon in adults with chronic insomnia

https://doi.org/10.1016/j.sleep.2011.06.008Get rights and content

Abstract

Objective

Ramelteon is an MT1/MT2 melatonin receptor agonist approved in the US and Japan for the treatment of sleep-onset insomnia. This study evaluated the effects of ramelteon 8 mg on patient reported sleep parameters in adults with chronic insomnia in an at-home setting using a post-sleep questionnaire-interactive voice response system (PSQ-IVRS).

Methods

Adults aged 18–64 years with chronic insomnia were randomized to receive ramelteon 8 mg or placebo nightly for 3 weeks. Sleep parameters were assessed via PSQ-IVRS within 60 min of awakening each morning. Adverse effects were collected throughout the study.

Results

A total of 552 subjects (mean age 43.2 years) received treatment (274 ramelteon, 278 placebo). There was a reduction in mean sleep latency at weeks 1, 2, and 3 compared with placebo but none reached statistical significance (−4.1 min, p = 0.088 week 1; −2.8 min, p = 0.258 week 2; −4.9 min, p = 0.060 week 3). There were no significant differences between placebo and ramelteon in other PSQ-IVRS sleep parameters. Only headache (18 [6.5%] placebo, 18 [6.6%] ramelteon) and somnolence (5 [1.8%], 12 [4.4%] ramelteon) occurred in > 3% of subjects.

Conclusions

Use of ramelteon 8 mg in an at-home setting did not demonstrate statistically significant improvements in subjective sleep latency compared with placebo, when measured by PSQ-IVRS.

Introduction

Insomnia is a condition characterized by difficulty falling asleep, difficulty maintaining sleep, or nonrestorative sleep [1]. Chronic insomnia (defined as symptoms persisting for greater than 1 month) affects approximately 10% of the adult population and is associated with significant daytime impairments or distress and an overall lower quality of life [2], [3].

Ramelteon is an MT1/MT2 melatonin receptor agonist approved in the US and Japan for the treatment of insomnia characterized by difficulty with sleep onset [4]. Ramelteon has a mechanism of action different from other prescription insomnia medications in the US. It acts through MT1 and MT2 melatonin receptors, which help regulate the body’s normal sleep–wake cycle, and does not cause general central nervous system sedation [5], [6]. In previous studies of adults with chronic insomnia, ramelteon has demonstrated the ability to significantly reduce objective latency to persistent sleep (LPS) [7], [8], [9], [10]. Reductions in subjective sleep onset latency have been less consistent [7], [9], [10], [11]. Overall, ramelteon is well tolerated with no evidence of consistent next-day residual effects, withdrawal, or potential for abuse [6], [7], [8], [9], [10], [11], [12], [13].

The reasons for the lack of consistent subjective efficacy with ramelteon may include methodological issues (i.e., evaluations at home vs. in the lab, sleep diary vs. questionnaire, compliance with medication timing, previous use of benzodiazepine receptor agonists), inherent population differences (i.e., age, geographic location), possible subjective overemphasis of sleep difficulties that are not detected when objective measurements are performed, or a result of ramelteon’s different mechanism of action (no general sedating effect). For these reasons, both objective and subjective measurements of sleep efficacy are used to provide important and complimentary information about the efficacy of sleep medications. This view is consistent with most regulatory bodies, which require both objective and subjective data for supporting the efficacy of hypnotics [14], [15].

This study was designed to evaluate the effects of ramelteon 8 mg in adults with chronic insomnia in an at-home setting using a post-sleep questionnaire-interactive voice response system (PSQ-IVRS). The PSQ-IVRS is a sleep questionnaire that was designed to address possible methodological issues in collecting subjective data from subjects at home and provide consistency in reporting.

Section snippets

Methods

Adults aged 18–64 years with chronic insomnia [1] were recruited for this study. Eligible subjects were required to report a habitual bedtime between 10 pm and 1 am with a history of subjective sleep latency (sSL)⩾60 min and a total subjective sleep time (sTST)⩽6.5 h. All subjects were required to adhere to a sleep schedule during the study (bedtime within 30 min of habitual bedtime, remaining in bed > 6.5 h nightly). Subjects were excluded from the study if they had experienced any recent sleep

Results

A total of 556 subjects were randomized, 247 (44.4%) were inpatients, and 309 (55.6%) outpatients. Of these, 552 subjects received treatment (274 ramelteon, 278 placebo) and 441 completed the study (212 ramelteon, 229 placebo). The mean age (SD) was 43.2 (12.5) years and the majority of subjects were women (357, 64.7%). A total of 176 subjects were identified in the PSG-validated subset (84 ramelteon, 92 placebo).

Overall there was a reduction in mean sSL at weeks 1, 2, and 3 compared with

Discussion

This study showed no significant improvements for ramelteon over placebo in subjective sleep measurements using the PSQ-IVRS in an at-home setting for adults with complaints of insomnia. However, a post hoc analysis of a subset of subjects whose sleep complaints were verified by PSG did show significant reductions in sSL at week 3. This suggests that the lack of consistent subjective efficacy with ramelteon may have more to do with the severity of the sleep disturbance of the population studied

Conflicts of Interest

The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: doi:10.1016/j.sleep.2011.06.008.

. ICMJE Form for Disclosure of Potential Conflicts of Interest form.

Acknowledgements

Assistance with writing and preparation of the manuscript was provided by Sara Sarkey, Ph.D., an employee of Takeda Pharmaceuticals North America. This study was funded by the Takeda Pharmaceutical Company, Ltd..

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