0374 Markers for Hypnotic Abuse Liability: Cortisol in Insomnia?

Abstract

Introduction: It is hypothesized that stress increases vulnerability to drug abuse. Some insomniacs show hyperarousal by increased physiological responses to stress, elevated alertness on the Multiple Sleep Latency Test (MSLT) and elevated diurnal NE concurrent with the MSLT elevation. Studies have reported cortisol elevation before sleep in insomnia vs controls. We sought to determine whether cortisol levels, both diurnal and pre-sleep, would vary as a function of MSLT and thus potentially serve as markers for hypnotic abuse liability. Materials and methods: DSM-IVR diagnosed insomniacs (N=110), aged 32-65 yrs, having no other sleep disorder, unstable medial or psychiatric diseases or drug dependency served as subjects. On a screening MSLT 26 had MSLTs ≤ 10 min (Lo) and 44 ≥15 min (Hi). Participants took 10 mg zolpidemor placebo, double-blind, nightly for 12 months. In months 1, 4, 8 and 12, urine was collected over 24 hrs in 8 hr- aliquots and assayed for cortisol (Ward Laboratories, Ann Arbor, MI). Saliva samples were collected 35 min before bedtime and drug administration in month 1 and 8, analyzed for cortisol levels (Salimetrics, State College, PA), and compared to a non-insomnia group (N=41). Results: Pre-sleep salivary cortisol was higher in insomniacs than controls (2.23+/-2.12 vs 1.49+/-0.91 ug/L, p < .04), was stable across months, and was not reduced with zolpidem. In self-administration assessments those with Hi MSLT increased the number of capsules (zolpidem or placebo) chosen over the 12 months. Conclusions: Hyperarousal (MSLT) is associated with higher daytime urinary cortisol levels and increased drug seeking. These data are consistent with our previous research showing daytime hypnotic selfadministration among Hi, but not Lo, MSLT insomniacs. This suggests that HiMSLT and its correlate elevated cortisol may be a potential hypnotic abuse marker among insomniacs.