Hyperarousal in insomnia: pre-sleep and diurnal cortisol levels in response to chronic zolpidem treatment

Abstract

Objectives: To determine whether cortisol levels, both diurnal and pre-sleep, would vary as a function of MSLT and would be reduced by nightly placebo versus zolpidem 10 mg.

Methods: DSM-IVR diagnosed subjects with insomnia (N = 95), aged 32-70 yrs, having no other sleep disorder, unstable medical or psychiatric diseases or drug dependency served. On a screening MSLT 27 had MSLTs <10 min (Lo) and 42 > 15 min (Hi). Participants took 10 mg zolpidem or placebo, double-blind, nightly for 12 months. In months one and 12 urine was collected over 24 h in 8 hr-aliquots and assayed for cortisol (Ward Laboratories, Ann Arbor, MI). Saliva samples were collected 35 min before bedtime and the 30 min drug administration in month one and eight, and analyzed for cortisol levels (Salimetrics, State College, PA).

Results: Pre-sleep salivary cortisol was higher in insomniacs than controls, but did not differ as a function of MSLT. Nightly zolpidem reduced pre-sleep cortisol relative to placebo on month one and eight, with no month effects or interaction. Diurnal (0700-1500 h) urinary cortisol was higher overall in the Hi vs Lo MSLT subjects with insomnia, was stable across months, and was not reduced with zolpidem.

Conclusions: Hyperarousal among subjects with insomnia as operationalized by MSLT is associated with higher diurnal urinary cortisol than those without hyperarousal, but not differential pre-sleep salivary cortisol. Zolpidem relative to placebo reduced pre-sleep salivary cortisol in all subjects, but not diurnal urinary cortisol.

Clinical trial: Safety and Efficacy of Chronic Hypnotic Use: http://www.clinicaltrials.gov NCT01006525.

Keywords: Insomnia; MSLT; Salivary cortisol; Urinary cortisol; Zolpidem.

Copyright © 2019 Elsevier B.V. All rights reserved.

Figures

Figure 1. Pre-sleep salivary cortisol in months 1 and 8 as a function of MSLT groups.

Means and SEM; No significant effects of MSLT group, months or interaction

Figure 2.. Pre-sleep salivary cortisol in months 1 and 8 as a function of Drug groups.

Means and SEM; Zol vs Pbo, p

Figure 3.. Daytime (0700–1500 hrs) urinary cortisol in months 1 and 12 as a function of MSLT.

Means and SEM; Hi vs Lo, p

Figure 4.. Daytime (0700–1500 hrs) urinary cortisol in months 1 and 12 as a function of Drug.

Means and SEM; No significant drug, month, or interaction effects