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Clinical Drug Investigation

, Volume 13, Issue 3, pp 134–144 | Cite as

Subjective Efficacy of Zolpidem in Outpatients with Chronic Insomnia

A Double-Blind Comparison with Placebo
  • Henry Lahmeyer
  • Charles S. Wilcox
  • Jules Kann
  • Ilo Leppik
Clinical Use

Summary

This multicentre, double-blind, randomised, placebo-controlled, parallel-group study compared the subjective hypnotic efficacy of nightly doses of zolpidem 10mg or zolpidem 15mg with that of placebo in patients with chronic insomnia. Patients received placebo or one of the zolpidem doses for 31 consecutive nights, followed by 4 nights of single-blind placebo administration. Self-reported subjective sleep latency (SSL), subjective total sleep time (SST) and other sleep-related parameters were collected via sleep questionnaires. SSL was significantly shorter in the zolpidem 10mg and 15mg groups than in the placebo group throughout active treatment. There was no significant difference between the two zolpidem groups. During the first week of double-blind treatment, SST was significantly longer in both zolpidem groups than in the placebo group, and remained numerically greater throughout active treatment. After discontinuation of zolpidem 10mg, SSL and SST were not significantly different from placebo at any time. Furthermore, SSL was numerically shorter and SST was numerically longer than at baseline. Adverse-event incidence rates were 43, 57 and 70% for the placebo, zolpidem 10mg and zolpidem 15mg groups, respectively. The most common events that occurred with greater frequency in the zolpidem groups than in the placebo group were drowsiness, lethargy and dizziness. It was concluded that administration of nightly doses of zolpidem 10mg to patients with chronic insomnia for 31 nights resulted in a continuous and significant reduction in SSL and in a persistent increase in SST, without the induction of tolerance during, or rebound insomnia after, this period.

Keywords

Adis International Limited Zolpidem Drug Invest Clinical Global Impression Sleep Latency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Dijk DJ, Duffy JF, Czeisler CA. Circadian and sleep/wake dependent aspects of subjective alertness and cognitive performance. J Sleep Res 1992; 1: 112–7PubMedCrossRefGoogle Scholar
  2. 2.
    Czeisler CA, Richardson GS. Detection and assessment of insomnia. Clin Ther 1991; 13(6): 663–79PubMedGoogle Scholar
  3. 3.
    National Institutes of Health Consensus Development Conference statement: the treatment of sleep disorders of older people. March 26–28, 1990. Sleep 1991; 14(2): 169–77Google Scholar
  4. 4.
    Langtry HD, Benfield P. Zolpidem: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential. Drugs 1990; 40: 291–313PubMedCrossRefGoogle Scholar
  5. 5.
    Benavides J, Peny B, Dubois A, et al. In vivo interaction of zolpidem with central benzodiazepine binding sites as labeled by [3H]Ro15-1788 in the mouse brain. Preferential affinity of zolpidem for the omega 1 subtype. J Pharmacol Exp Ther 1988; 245: 1033–41PubMedGoogle Scholar
  6. 6.
    Langer SZ, Arbilla S, Scatton B, et al. Receptors involved in the mechanism of action of zolpidem. In: Sauvanet JP, Langer SZ, Morselli PL, editors. Imidazopyridines in sleep disorders. New York: Raven, 1988: 55–70Google Scholar
  7. 7.
    Benavides J, Peny B, Durand A, et al. Comparative in vivo and in vitro regional selectivity of central omega (benzodiazepine) site ligands in inhibiting (3H)flumazenil binding in the rat central nervous system. J Pharmacol Exp Ther 1992; 263(2): 884–96PubMedGoogle Scholar
  8. 8.
    Benavides J, Peny B, Ruano D, et al. Comparative autoradiographic distribution of central omega (benzodiazepine) modulatory site subtypes with high, intermediate and low affinity for zolpidem and alpidem. Brain Res 1993; 604(1–2): 240–50PubMedCrossRefGoogle Scholar
  9. 9.
    Roth T, Roehrs T, Vogel G. Zolpidem in the treatment of transient insomnia: a double-blind, randomized comparison with placebo. Sleep 1995; 18(4): 246–51PubMedGoogle Scholar
  10. 10.
    Walsh JK, Schweitzer PK, Sugerman JL, et al. Transient insomnia associated with a 3-hour phase advance of sleep time and treatment with zolpidem. J Clin Psychopharmacol 1990; 10(3): 183–9CrossRefGoogle Scholar
  11. 11.
    Schlich D, L’Heritier C, Coquelin J, et al. Long-term treatment of insomnia with zolpidem. J Int Med Res 1991; 19: 271–9PubMedGoogle Scholar
  12. 12.
    Nicholson AN, Pascoe PA. Hypnotic activity of an imidazo-pyridine (zolpidem). Br J Clin Pharmacol 1986: 21: 205–11PubMedCrossRefGoogle Scholar
  13. 13.
    Scharf MB, Mayleben DW, Kaffeman M, et al. Dose response effects of zolpidem in normal geriatric subjects. J Clin Psychiatry 1991; 52: 77–83PubMedGoogle Scholar
  14. 14.
    Scharf MB, Roth T, Vogel GW, et al. A multicenter, placebo-controlled study evaluating zolpidem in the treatment of chronic insomnia. J Clin Psychiatry 1994; 55: 192–9PubMedGoogle Scholar
  15. 15.
    Kryger MH, Steljes D, Pouliot Z, et al. Subjective versus objective evaluation of hypnotic efficacy: experience with zolpidem. Sleep 1991; 14(5): 399–407PubMedGoogle Scholar
  16. 16.
    Rao CR. Linear statistical inference and its application. 2nd ed. New York: John Wiley & Sons, 1973CrossRefGoogle Scholar
  17. 17.
    Cox DR. Regression models and life tables. JR Stat Soc Series B (Methodological) 1972; 34: 187–220Google Scholar
  18. 18.
    Kaplan EL, Meier P. Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–81CrossRefGoogle Scholar
  19. 19.
    Miller RG. Survival analysis. New York: John Wiley & Sons, 1981: 70–6Google Scholar
  20. 20.
    Hoelscher TJ, Edinger JD. Treatment of sleep maintenance insomnia in older adults. Psychol Aging 1988; 3: 258–63PubMedCrossRefGoogle Scholar
  21. 21.
    Roehrs T, Vogel G, Roth T. Rebound insomnia: its determinants and significance. Am J Med 1990; 88 Suppl. 3A: 39S–42SPubMedGoogle Scholar
  22. 22.
    Roth T, Roehrs T. Issues in the use of benzodiazepines. J Clin Psychiatry 1992; 53(6): 14–8PubMedGoogle Scholar
  23. 23.
    Lader M. Rebound insomnia and newer hypnotics. Psychopharmacology 1992; 108: 248–55PubMedCrossRefGoogle Scholar
  24. 24.
    Merlotti L, Roehrs T, Zorick F, et al. Rebound insomnia: duration of use and individual differences. J Clin Psychopharm 1991; 11(6): 368–73CrossRefGoogle Scholar
  25. 25.
    Mitler MM, Seidel WF, Van Den Hoed J, et al. Comparative hypnotic effects of flurazepam, triazolam and placebo: a long-term simultaneous nighttime and daytime study. J Clin Psychopharm 1984; 4(1): 2–13CrossRefGoogle Scholar
  26. 26.
    Roehrs TA, Roth T, Scharf M, et al. Rebound insomnia potential of zolpidem 10mg as evaluated by three different methods [abstract]. Sleep Res 1992; 21: 69Google Scholar

Copyright information

© Adis International Limited 1997

Authors and Affiliations

  • Henry Lahmeyer
    • 1
  • Charles S. Wilcox
    • 2
  • Jules Kann
    • 3
  • Ilo Leppik
    • 4
  1. 1.University of Illinois HospitalChicagoUSA
  2. 2.Pharmacology Research InstituteLong BeachUSA
  3. 3.Biodecision LaboratoriesPittsburghUSA
  4. 4.University of MinnesotaMinneapolisUSA

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