Long-Term, Non-Nightly Administration of Zolpidem in the Treatment of Patients With Primary Insomnia

Michael L. Perlis, Ph.D.; W. Vaughn McCall, M.D.; Andrew D. Krystal, M.D., M.S.; and James K. Walsh, Ph.D.

Introduction: While it is common practice that hypnotics are used on a non-nightly basis, few investigations have been undertaken to evaluate the efficacy of the intermittent dosing strategy. The present study was designed to further evaluate this issue within a large scale, double-blind, placebo-controlled, long-term trial.

Method: Patients who met DSM-IV criteria for primary insomnia participated in the study from January 2000 through October 2001. Patients were randomly assigned to 1 of 2 treatment groups (zolpidem 10 mg or placebo) for a period of 12 weeks. Ten pills were provided in foil packs on an every-other-week basis, and patients were instructed to take no fewer than 3 and no more than 5 pills per week. Sleep was evaluated daily with sleep diaries. Pill use was recorded in the sleep diaries.

Results: 199 patients (mean +/- SD age = 41.0 +/- 12.8 years; 71% female) were randomly assigned to treatment. On mean, patients receiving zolpidem exhibited (vs. baseline) a 42% decrease in sleep latency, a 52% reduction in number of awakenings, a 55% decrease in wake time after sleep onset, and a 27% increase in total sleep time. These positive clinical gains did not diminish with time and were not associated with dose escalation. There was also no evidence of rebound insomnia.

Conclusions: Over a period of 12 weeks of intermittent treatment with zolpidem, sleep continuity was significantly improved, the clinical gains were sustained, and there was no evidence of subjective rebound insomnia between doses or increases in the amount of medication used during the study interval.

(J Clin Psychiatry 2004;65:1128-1137)

Received Feb. 3, 2004; accepted June 1, 2004. From the Sleep and Neurophysiology Laboratory, Department of Psychiatry, University of Rochester, and the University of Rochester Medical Center, Neurosciences Program, Rochester, N.Y. (Dr. Perlis); the Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, N.C. (Dr. McCall); Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, N.C. (Dr. Krystal); and the Sleep Medicine and Research Center, St. John's/St. Luke's Hospitals and the Department of Psychology, Saint Louis University, St. Louis, Mo. (Dr. Walsh).

Research was supported by Lorex (a member of the Sanofi-Synthelabo Group, New York, N.Y.). Interpretation of study data and manuscript preparation were solely the responsibilities of the authors.

Financial disclosure and a list of study investigators appear at the end of this article.

Corresponding author and reprints: Michael L. Perlis, Ph.D., Sleep and Neurophysiology Laboratory, Department of Psychiatry, University of Rochester, and the University of Rochester Medical Center, Neurosciences Program, 300 Crittenden Blvd., Rochester, NY 14642(e-mail: Michael_Perlis@URMC.Rochester.edu).