Original article Long-term use of sedative hypnotics in older patients with insomnia Sonia Ancoli-Israel a,1, * , Gary S. Richardson b,1 , Richard M. Mangano c,2 , Lisa Jenkins d,2 , Phil Hall d,2 , Walter S. Jones e,2 a Department of Psychiatry 116A, University of California San Diego and Veterans Affairs, San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA 92161, USA b Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA c Neuroscience Clinical Research and Development, Wyeth Research, USA d Clinical Biostatistics, Wyeth Research, USA e ImpartMed Received 11 February 2004; received in revised form 25 October 2004; accepted 28 October 2004 Abstract Background and purpose: Insomnia is a common problem that increases with age and can last months to years. While substantial data establish the efficacy and safety of short-acting hypnotic therapy for the management of short-term insomnia using benzodiazepines receptor agonists (BzRAs), there are few studies on the continued efficacy and safety of these drugs when used for sustained periods. This paper reports the results of a 1-year open-label extension phases of two randomized, double-blind trials of zaleplon. Patients and methods: In the open-label phase, older patients self-administered zaleplon nightly from 6 to 12 months and were then followed through a 7-day single-blind placebo-controlled run-out period. Results: The safety profile in this population of older adults was similar to that observed in a short-term trial of an equivalent population. The data also suggested that long-term therapy produced and maintained statistically significant improvement in time to persistent sleep onset, duration of sleep and number of nocturnal awakenings (P!0.001 for each variable) for treatment durations of up to 12 months. Discontinuation was not associated with rebound insomnia. Conclusion: The open-label trial of long-term hypnotic therapy with zaleplon 5 and 10 mg suggests that they are safe and effective for the treatment of insomnia in older patients. Placebo-controlled, double-blind trials are needed in zaleplon and other BzRAs to confirm these results. q 2004 Elsevier B.V. All rights reserved. Keywords: Aging; Insomnia; Sedative hypnotic; Withdrawal; Zaleplon 1. Introduction The prevalence of insomnia increases with age to the point that approximately half of individuals age 65 and over are affected at least a few nights per month [1–4]. These sleep disturbances are associated with daytime drowsiness that manifests as both intentional and inadvertent naps, and can result in impaired cognitive functioning and motor skills, diminished quality of life [5], and increased consumption of health care resources [6]. Benzodiazepine receptor agonists (BzRAs) are com- monly used to treat insomnia in older patients [7,8]. Although safety and efficacy have been established for these agents when used for short-duration therapy both in the younger [9–13] and older population [14], there are few data that establish their continued efficacy and safety in long-term use. The lack of data supporting long-term therapy limits access to potentially effective treatment of a significant medical problem. In the first long-term study of efficacy, Krystal et al. [15] followed young and middle-aged patients with chronic 1389-9457/$ - see front matter q 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2004.10.015 Sleep Medicine 6 (2005) 107–113 www.elsevier.com/locate/sleep * Corresponding author. Tel.: C1 858 642 3828; fax: C1 858 552 7536. E-mail address: sancoliisrael@ucsd.edu (S. Ancoli-Israel). 1 Drs Ancoli-Israel and Richardson are on the Scientific Advisory Boards for Wyeth and for King Pharmaceuticals. 2 Drs Magnano, Jenkins, and Hall and Walter Jones are employed by Wyeth.