Hyperarousal in insomnia and hypnotic dose escalation

Abstract

Background: Given concerns about the abuse liability of hypnotics, this study assessed hyperarousal in people with insomnia and its relation to hypnotic self-administration over 12 months of nightly hypnotic use.

Methods: Ninety-five subjects with insomnia (age 32-64 years) underwent screening nocturnal polysomnogram (NPSG) and Multiple Sleep Latency Test (MSLT) the following day and, then, were randomized to receive zolpidem 10 mg or placebo nightly for 12 months. NPSGs and MSLTs were conducted and urine was collected (0700-1500 h) and analyzed for norepinephrine (NE) levels during months one and eight on study medication. A subset (n = 54) underwent hypnotic self-administration assessments in months one, four, and 12.

Results: Mean daily sleep latency on screening MSLT was distributed across the full range of MSLT latencies (2-20 min). The highest screening MSLT latencies were detected in subjects with higher NE levels, compared to those with the lowest MSLT latencies. In the subset undergoing self-administration assessment, those with the highest MSLT latencies chose more capsules (placebo and zolpidem) and increased the number of capsules chosen in months four relative to month one, compared to those with the lowest MSLT latencies.

Conclusions: These data show that some insomniacs are hyperaroused with high MSLT/NE levels and, compared to low MSLT/NE insomniacs, they increase the number of capsules (zolpidem and placebo) self-administered on months four and 12 relative to Month one.

Trial registration: ClinicalTrials.gov NCT01006525.

Keywords: Hypnotic self-administration; Insomnia; MSLT; NE.

Conflict of interest statement

Conflicts: T. Roehrs: consultant – Lundbeck, Pfizer; speaker – Pernix; grantee – Merck T. Roth: consultant – Actelion, Addrenex, Cephalon, Eisai, Intec, Merck, Pfizer, Sanofi, Sepracor, Shire, Somaxon, TransOral; speaker – Cephalon, Sanofi; grantee – Merck

Copyright © 2016 Elsevier B.V. All rights reserved.

Figures

Figure 1

Daytime (0700–1500 hrs) urinary norepinephrine (NE) in people with insomnia and Hi MSLT (≥15 min) latencies vs Lo MSLT (≤ 10 min) latencies (p <.03>

Figure 2

Change in number of capsules chosen (placebo and zolpidem) from month 1 to month 4 and month 12 in Hi and Lo MSLT groups (p<.08>