Holbrook: Treatment of primary insomnia [CMAJ

Treatment of primary insomnia

CMAJ 2000;163(4):390-91

In response to: J. Montplaisir

See also:

eLetters

Although Jacques Montplaisir may be correct in his assertion that shorter and longer acting benzodiazepines differ in their profiles of adverse effects on the central nervous system, this was not evident in our systematic review [Review].¹ Many of the studies published on amnesia and rebound insomnia have involved triazolam, a potent benzodiazepine with one of the shortest half-lives of the group. However, these and other cognitive impairment effects have been ascribed to all benzodiazepines.^2,3 We remind readers that no benzodiazepine is reliably short acting in terms of sedation in elderly patients with comorbidity, particularly if doses are not adjusted downward.^4,5,6 There has been virtually no research on therapeutic strategies for insomnia involving this group of patients, who are arguably the highest per capita users of benzodiazepines and alternatives.

Zopiclone is an interesting nonbenzodiazepine sedative. Unlike Montplaisir, we are not convinced that it is superior in efficacy or safety to all benzodiazepines. Studies involving zopiclone tend to be disabled by the use of suboptimal benzodiazepines for comparison (very-long-acting benzodiazepines are used instead of shorter acting drugs similar to zopiclone), small patient numbers and concerns regarding dose equivalence. Our systematic review of 9 randomized controlled trials including 3 appropriate for meta-analysis did not suggest that zopiclone is superior for sleep.¹ A separate meta-analysis of sleep laboratory studies also noted the paucity of high-quality studies involving zopiclone, but the available studies suggest that it is similar to shorter acting benzodiazepines in efficacy, tolerance and rebound.⁷ Several studies have noted that zopiclone has adverse effects on human performance similar to those seen with benzodiazepines.^8,9,10,11 Finally, although it represents a lower quality of evidence according to our criteria, we are highly persuaded by the zopiclone manufacturer's own product monograph (monographs are often based on information not available for public scrutiny) that "the pharmacological profile of zopiclone is similar to that of the benzodiazepines."¹²

Anne Holbrook
Renée Labiris
Centre for Evaluation of Medicines
St. Joseph's Hospital
Hamilton, Ont.

References

    1.    Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ 2000;162(2):225-33.

    2.    Greenblatt DJ, Shader RI, Abernethy DR. Drug therapy: current status of benzodiazepines (first of two parts). N Engl J Med 1983;309:354-8. [MEDLINE]

    3.    Greenblatt DJ, Shader RI, Abernethy DR. Drug therapy: current status of benzodiazepines (second of two parts). N Engl J Med 1983;309:410-6. [MEDLINE]

    4.    Canadian Pharmacists Association. Benzodiazepines. General monograph. In: Compendium of Pharmaceuticals and Specialties. 35th ed. Ottawa: Canadian Pharmacists Association; 2000. p. 187-9.

    5.    Ariano RE, Kassum DA, Aronson KJ. Comparison of sedative recovery time after midazolam versus diazepam administration. Crit Care Med 1994;22:1492-6. [MEDLINE]

    6.    Platten HP, Schweizer E, Dilger K, Mikus G, Klotz U. Pharmacokinetics and the pharmacodynamic action of midazolam in young and elderly patients undergoing tooth extraction. Clin Pharmacol Ther 1998;63:552-60. [MEDLINE]

    7.    Soldatos CR, Dikeos DG, Whitehead A. Tolerance and rebound insomnia with rapidly eliminated hypnotics: a meta-analysis of sleep laboratory studies. Int Clin Psychopharmacol 1999;14:287-303. [MEDLINE]

    8.    Griffiths AN, Jones DM, Richens A. Zopiclone produces effects on human performance similar to flurazepam, lormetazepam and triazolam. Br J Clin Pharmacol 1986;21:647-53. [MEDLINE]

    9.    Bocca ML, Le Doze F, Etard O, Pottier M, L'Hoste J, Denise P. Residual effect of zolpidem 10 mg and zopiclone 7.5 mg versus flunitrazepam 1 mg and placebo on driving performance and ocular saccades. Psychopharmacology (Berl) 1999;143:373-9. [MEDLINE]

    10.    Mattila MJ, Vanakoski J, Kalska H, Seppala T. Effects of alcohol, zolpidem, and some other sedatives and hypnotics on human performance and memory. Pharmacol Biochem Behav 1998;59:917-23. [MEDLINE]

    11.    Yamadera H, Tsukahara Y, Kato M, Okuma T. Zopiclone pharmacodynamics: by monitoring event-related potentials and psychometric scores. Nihon Shinkei Seishin Yakurigaku Zasshi 1996;16:145-9. [MEDLINE]

    12.    Rhône-Poulenc Rorer. Imovane. In: Compendium of Pharmaceuticals and Specialties. 35th ed. Ottawa: Canadian Pharmacists Association; 2000. p. 736- 7.