Montplaisir: Treatment of primary insomnia [CMAJ

Treatment of primary insomnia

CMAJ 2000;163(4):389-90

See response from: A. Holbrook, R. Labiris

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eLetters

A major problem with the meta-analysis by Anne Holbrook and colleagues of benzodiazepine use in the treatment of insomnia [Review]¹ is that benzodiazepines were considered as a single medication; this class of drugs in fact consists of several compounds with marked differences in pharmacokinetics and side-effect profiles. Patients may be prescribed short-, intermediate- or long-acting compounds. Among other side effects, short-acting benzodiazepines cause daytime anxiety, amnesia and rebound insomnia upon withdrawal, whereas long-acting compounds cause residual sleepiness and cognitive impairments. Because the side effects differ so much from one compound to the next, those of benzodiazepines were not found to differ significantly from those of either a placebo or other insomnia treatments in the meta-analysis, which pooled studies investigating different benzodiazepines. They are nevertheless of prime importance for the clinician who has to choose a single hypnotic.

These side effects, especially the residual sleepiness and cognitive impairments, considerably limit the clinical use of benzodiazepines. As a result, several controlled studies have concluded that zopiclone should be recommended in ambulant or out-patient populations.^2,3 The effects of hypnotics on breathing during sleep should also be considered. There are several indications that benzodiazepines depress respiration during sleep whereas zopiclone does not.^4,5,6,7 This is important, especially in patients with chronic obstructive pulmonary disease, sleep apnea syndrome and upper airway resistance and, to a certain extent, in people who snore. Another clinical indication of zopiclone is its usefulness in the treatment of benzodiazepine dependency.^8,9,10 Finally, a major advantage of zopiclone is that, unlike most benzodiazepines, it does not modify sleep architecture (most benzodiazepines reduce both slow-wave and REM sleep).^6,11

I agree with Anne Holbrook and colleagues that nonpharmacological treatments are the treatment of choice for chronic primary insomnia.¹ However, when comparing hypnotics, I believe that zopiclone has several advantages over each benzodiazepine taken separately.

Jacques Montplaisir
Sleep Disorders Centre
Hôpital du Sacré-Cœur de Montréal
Montreal, Que.

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.    Ponciano E, Freitas F, Camara J, Faria M, Barreto M, Hindmarch I. A comparison of the efficacy, tolerance and residual effects of zopiclone, flurazepam and placebo in insomniac patients. Int Clin Psychopharmacol 1990;5(Suppl 2):69-77. [MEDLINE]

    3.    Anderson AA. Zopiclone and nitrazepam: a multicenter placebo controlled comparative study of efficacy and tolerance in insomniac patients in general practice. Sleep 1987;10(Suppl 1):54-62. [MEDLINE]

    4.    Model DG. Nitrazam induced respiratory depression in chronic obstructive lung disease. Br J Dis Chest 1973;67:128-130. [MEDLINE]

    5.    Dolly FR, Block AJ. Effect of flurazepam on sleep-disordered breathing and nocturnal oxygen desaturation in asymptomatic patients. Am J Med 1984;73:239-43.

    6.    Muir JF, deFouilloy C, Broussier P, Locquet R, Maillard F. Comparative study of the effects of zopiclone and placebo on respiratory function in patients with chronic obstructive respiratory insufficiency. Int Clin Psychopharmacol 1990;5(Suppl 2):85-94. [MEDLINE]

    7.    Lofaso F, Goldenberg F, Thebault C, Janus C, Harf A. Effect of zopiclone in sleep, night time ventilation and daytime vigilance in upper airway resistance syndrome. Eur Respir J 1997;10:2573-7. [MEDLINE]

    8.    Shapiro CM, Sherman D, Peck DF. Withdrawal from benzodiazephines by initiating switching to zopiclone. Eur Psychiatry 1995;10(Suppl 3):145-51.

    9.    Lemoine P, Ohayon MM. Is hypnotic withdrawal facilitated by the transitory use of a substitute drug? Prog Neuropsychopharmacol Biol Psychiatry 1997;21:111-24. [MEDLINE]

    10.    Pat-Horenczyk R, Hacohen D, Herer P, Lavie P. The effects of substituting zopiclone in withdrawal from chronic use of benzodiazepine hypnotics. Psychopharmacol (Berl) 1998;140:450-7.

    11.    Gaillard JM. Benzodiazepines and gaba-ergic transmission. In: Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep medicine. 2nd ed. Philidelphia: WB Saunders; 1994. p. 349-54.