Skip to main content
Canadian Family Physician logoLink to Canadian Family Physician
. 2007 Dec;53(12):2124–2129.

Zopiclone

Is it a pharmacologic agent for abuse?

Nevio Cimolai 1,
PMCID: PMC2231551  PMID: 18077750

Abstract

OBJECTIVE

To determine whether the hypnosedative drug zopiclone could be an agent for abuse.

SOURCES OF INFORMATION

Using MEDLINE and PubMed, English-language medical literature was systematically reviewed for reports of direct drug abuse and addiction. A review was also conducted for clinical trials or patient series that discussed issues of addiction or rebound effects.

MAIN MESSAGE

Evidence of drug abuse and dependency was found in case reports and small patient series. Dependency symptoms of severe rebound, severe anxiety, tremor, palpitations, tachycardia, and seizures were observed in some patients after withdrawal. Abuse occurred more commonly among patients with previous drug abuse or psychiatric illnesses. Many clinical trials have found evidence of rebound insomnia after recommended dosages were stopped, albeit for a minority of patients. Comparative studies of zopiclone and benzodiazepines or other “Z” drugs are conflicting.

CONCLUSION

Zopiclone has the potential for being an agent of abuse and addiction. While many have suggested that the addictive potential for this and other “Z” drugs is less than for most benzodiazepines, caution should be taken when prescribing this agent for insomnia. Ideally, prescriptions should be given for a short period of time and within the recommended dosage guidelines.

Case

A 49-year-old man presented to an outpatient clinic with complaints of chronic insomnia. He was known to have an obsessive-compulsive disorder and was seen frequently in conjunction with a psychiatrist. He had been taking zopiclone for approximately 5 years. Initially, he was given 7.5 mg nightly, but this dose increased to 15 mg and then 22.5 mg.

The patient claimed that he was using only the prescribed amount, but he had been prescribed 60 tablets only 11 days earlier. Review of pharmacy records revealed that the patient had been prescribed approximately 500 tablets (7.5 mg) during the previous 100 days. When confronted with this information, the patient admitted to taking 4 to 7 tablets every night and afterward admitted he was addicted to zopiclone. Trials of trazodone and amitriptyline were then prescribed as he attempted to reduce the zopiclone doses. Regular follow-up visits were also recommended to help him manage his addiction.

Zopiclone is a commonly used hypnosedative that has been mainly promoted as a sleep aid.1 It is available in several generic formulations in Canada but has been marketed under the trade names Imovane and Rhovane.

Zopiclone is one of the “Z” drug sedative-hypnotics and became clinically available in the mid 1980s. (Others include zaleplon [Starnoc in Canada and Sonata in the United States], zolpidem [Ambien in the United States], and eszopiclone [S-isomer of zopiclone; Lunesta in the United States].) It is not one of the benzodiazepine drugs but has many similarities to them when used for sleep. These include decreased latency to sleep initiation, increased duration of sleep, and reduced episodes of awakening. There was hope that “Z” drugs would be less addictive or less associated with post-use rebound than benzodiazepines.2

Chemically, zopiclone is a cyclopyrrolone.3 It is a type A γ-aminobutyric acid (GABA) receptor agonist and therefore enhances GABA-related neuronal inhibition. Benzodiazepines also bind to and affect the function of GABA receptors. Few interactions with other drugs are documented.4 Zopiclone is typically prescribed in the range of 5 mg to 7.5 mg daily and at 3.75 mg daily for the elderly.

While zopiclone is a highly effective sleep aid, there is controversy about the extent of its addiction potential. In practice, zopiclone is often used for treating insomnia, but it is not uncommon for patients with drug-seeking behaviour to request it. Although recommended for short-term treatment of insomnia,5 it is also not uncommon for patients, including the elderly, to take the drug nightly or continuously for many months. When discussing potential addiction to zopiclone use with their physicians, some prospective patients say they have been told it is not addictive.

The costs and consequences of insomnia in the Canadian population have been estimated.6 From 5% to 30% of any particular population might be affected. In response, a considerable amount of hypnosedatives is prescribed yearly. Studies show the use of benzodiazepines and “Z” drugs to be as high as 5% to 30% among the elderly.7,8

Sources of information

Using MEDLINE and PubMed, English-language medical literature was systematically reviewed for reports of direct drug abuse and addiction. A review was also conducted for clinical trials or patient series that discussed issues of addiction or rebound effects.

Main message

Zopiclone has quickly gained acceptance by practitioners and patients.9 In Alberta it is now the most frequently dispensed hypnosedative agent (47.4% of such agents compared with 0.1% to 28.7% for individual benzodiazepines).10 Investigators have found substantial increases in the use of zopiclone in Canada in the years 1996–1997, 1998–1999, and 2000–2001.11 It appears that the increases might have come at the expense of declining use of some benzodiazepines. In a 2003 lay review12 of Canadian pharmaceuticals, zopiclone ranked 30th among the top 100 generic drug products sold (nearly 1.5 million prescriptions of generic zopiclone), and the brand name Imovane ranked 74th (more than 500 000 prescriptions) of 100 brand-name drug products sold in Canada; only Ativan ranked higher (14th; approximately 2.5 million prescriptions) as a brand-name hypnosedative.12

Initial reports have proposed that zopiclone did not cause rebound or withdrawal phenomena or dependence.1315 Postmarketing surveillance reports have been favourable.16,17 Some have indicated that “Z” drugs were less likely to be habit forming than benzodiazepines.1820 However, animal data support the potential for addiction.21 Although not much has been published on this topic, a somewhat different picture has emerged with the few anecdotes, case series, and controlled studies. Parallels with other addictive substances have been heralded and reviewed.22,23

Table 1 provides examples of zopiclone abuse and addiction.2431 In some circumstances, the drug was initiated at a standard dose of 7.5 mg daily but then increased. Most patients taking the drug suffered from pre-existing addiction or chemical abuse, or from underlying psychiatric disorders. Withdrawal symptoms were reported in several of these anecdotes, including cravings, severe rebound insomnia, anxiety or panic attacks, weakness, tremor, palpitations, and tachycardia. Withdrawal seizures were also recorded.

Table 1.

Patient reports of zopiclone abuse or addiction

REPORT PATIENT SEX PATIENT AGE MG/D UNDERLYING PROBLEMS ADDICTION OR ABUSE HISTORY COMMENTS
Sutherland,24 1991 Male 29 7.5 None reported Narcotic Relapsed with a narcotic addiction
Aranko et al,25 1991 Male 36 30 to 90 Depression, obsessive-compulsive disorder Alcohol, benzodiazepines Had withdrawal seizures
Thakore and Dinan,26 1992 Male 36 37.5 to 45 Affective disorder Alcohol, benzodiazepines
Sullivan et al,27 1995 Male 17 15 to 30 None reported Multidrug Better than temazepam when used with alcohol
Sullivan et al,27 1995 Male 16 7.5 to 37.5 Behavioural problems Alcohol
Sullivan et al,27 1995 Male 18 Intravenous use None reported Multidrug
Jones and Sullivan,28 1998 Male 29 22.5 None reported None reported Multiple withdrawal symptoms
Jones and Sullivan,28 1998 Male 26 30 None reported None reported Multiple withdrawal symptoms
Jones and Sullivan,28 1998 Female 49 22.5 None reported None reported Rebound anxiety and insomnia
Jones and Sullivan,28 1998 Female 36 30 Bipolar disorder Benzodiazepines Multiple withdrawal symptoms
Sikdar,29 1998 Male and female (6 patients) Various 45 to 390 None reported None reported Multiple withdrawal symptoms, tolerance; 2 patients forged prescriptions
Ayonrinde and Sampson,30 1998 Female 60 22.5 Schizophrenia Alcohol, benzodiazepines Multiple withdrawal symptoms
Ayonrinde and Sampson,30 1998 Male 40 30 Depression None reported Multiple withdrawal symptoms
Ayonrinde and Sampson,30 1998 Female 71 15 Depression None reported Multiple withdrawal symptoms
Flynn and Cox,31 2006 Female 76 67.5 Depression None reported Had withdrawal seizures

Addicts report that ingesting zopiclone and alcohol together heightens euphoria.27 In one report,24 use of zopiclone appeared to instigate a relapse into narcotic use. The drug has become well known in addict circles,32 and in the United Kingdom, the tablets have been labeled as zim-zims.27 Drug abusers have also used zopiclone as a replacement for benzodiazepines. With many generic versions becoming available, the cost of zopiclone on the street has decreased. Oral use of zopiclone predominates, but intravenous use has also been reported. In clinical practice, other patients are possibly at risk for dependence, especially after prolonged use.

Table 2 also provides some insight from various studies.3250 Some of the data pose contradictions; however, rebound insomnia and withdrawal symptoms soon after cessation are not uncommon whether patients took the usual dose or excessive doses. Symptoms might also occur despite a tapering of the dose. As with benzodiazepines, zopiclone was recognized as a potential replacement for alcohol. These phenomena occurred with what would have been considered standard daily doses. One addiction centre reported that 5.1% of addicts presenting to addiction centres admitted to zopiclone addiction.50

Table 2.

Studies addressing withdrawal or addiction associated with zopiclone

STUDY NO. OF PATIENTS MG/D STUDY GROUP FINDINGS
Mamelak et al,33 1982 6 7.5 Insomniac patients Zopiclone, treated for 3 wk, no carry over effect and no rebound insomnia
Dorian et al,34 1983 9 7.5 Normal volunteers Double-blind placebo controlled, treated for 3 wk, increased anxiety and lighter sleep on withdrawal for days shortly after discontinuation
Lader and Denney,35 1983 10 2.5 to 10 Normal volunteers Double-blind placebo controlled, dose response curve for residual overnight effects as determined with electroencephalogram and psychological tests
Bechelli et al,36 1983 40 3.75 Weaned alcoholics Zopiclone vs triazolam, double-blind randomized crossover, zopiclone use likened to alcohol use, more likely to choose zopiclone over triazolam
Boissl et al,37 1983 40 3.5 Weaned alcoholics Zopiclone vs triazolam, double-blind randomized crossover, no difference in replacement potential for alcohol
Lader and Frcka,38 1987 10 3.75 to 7.5 Normal volunteers Zopiclone and placebo and temazepam, double-blind comparisons, zopiclone rebound effects minimal, withdrawal of total dose no different than tapering
Fleming et al,39 1990 48 7.5 Chronic insomniacs Zopiclone vs triazolam, double-blind, worse psychomotor deterioration after triazolam than zopiclone, 3 of 24 zopiclone patients felt agitated early after withdrawal
Ponciano et al,40 1990 24 7.5 Chronic insomniacs Zopiclone and placebo and _urazepam, double-blind randomized, treated for 3 wk, zopiclone has no effect on early morning performance and free of residual sedative activity
Ngen and Hassan,41 1990 15 7.5 Insomniac patients Zopiclone and placebo and temazepam, randomized study, treated for 2 wk, no psychomotor performance deterioration
Pecknold et al,42 1990 11 7.5 Chronic insomniacs Treated for 7 to 8 wk, return of sleep variables to pretreatment baseline after withdrawal, 1 of 11 patients had marked rebound insomnia and daytime anxiety for the first wk off
Begg et al,43 1992 88 7.5 General sleep disorder Zopiclone vs midazolam, treated for 1 wk, more rebound insomnia with zopiclone
Lemoine et al,44 1995 102 7.5 Chronic insomniacs Treated for 3 mo, withdrawal effects despite tapering dose
Mann et al,45 1996 11 7.5 Normal volunteers Treated for 12 d, rebound insomnia after discontinuation, increased REM sleep after discontinuation, no effect on nocturnal melatonin secretion
Sikdar and Ruben,32 1996 100 90 to 380 Multidrug abusers Strong cravings, feeling edgy, rebound insomnia, tolerance to sedative properties
Stip et al,46 1999 20 7.5 Insomniac patients Zopiclone and placebo and temazepam, double-blind, treated for 3 wk, no rebound insomnia or anxiety with either
Voderholzer et al,47 2001 11 7.5 Normal volunteers Zopiclone and zolpidem and triazolam and placebo, double-blind, treated for 4 wk, minimal rebound effects
Tsutsui et al,48 2001 248 7.5 Insomniac patients Zopiclone vs zolpidem, treated for 2 wk, zopiclone group had 15.4% with rebound insomnia
Johansson et al,49 2003 23
120
Not reported Alcoholics
Controls
Alcoholics more often dependent on zopiclone than controls
Jaffe et al,50 2004 297 Not reported Addiction treatment centres 5.1% claimed to be addicted to zopiclone

Zopiclone will continue to be prescribed for insomnia given that most believe, generally and scientifically, that it is associated with fewer clinical problems than benzodiazepines.18 Some even believe zopiclone is not addictive at all. In a recent, although small, survey51 of 40 British psychiatrists, zopiclone was found to be commonly prescribed; however, many respondents were unaware of its dependence potential. The Compendium of Pharmaceuticals and Specialties warns of potential addiction.5 It also recommends limiting the agent’s use (to approximately 7 to 10 days). Although the initial manufacturer’s recommendations include limits for length of therapy, long-term use in geriatric or general populations is not uncommon.

Some have argued that the frequency of “Z” drug misuse must be low given the many prescriptions written and the few case reports published worldwide.52 However, an Internet source53 has enumerated 24 people who have sought advice regarding zopiclone dependency, and this number rivals the total available case reports cited worldwide in the medical literature. Because some drug abusers do not seek treatment, the true frequency of abuse or dependence is certainly higher than reported.

Conclusion

Physicians prescribing zopiclone should have the same concerns as they would for prescribing benzodiazepines (Table 354). Ideally, use should be short-term; long-term use must be monitored carefully. Physicians are also advised to be cautious about giving prescriptions to patients who misuse alcohol or drugs. A direct and especially new request for zopiclone should raise concern for potential abuse. Such abuse might include personal use or sale of the drug on the street. Physicians could try low-dose antidepressants, such as amitripty-line or trazodone, if a pharmacologic agent is absolutely required for insomnia.

Table 3.

Points to consider when prescribing hypnosedative drugs

  1. Have nonpharmacologic approaches or therapies been considered?

  2. Is a pharmacologic agent required?

  3. Is the target short-term therapy? Is the target long-term therapy?

  4. Are there medical or drug interaction contraindications?

  5. Is the most cost-effective and safe treatment being considered (ie, dose, type of medication, compliance, and age considerations)?

  6. Is insomnia part of an underlying illness that will require some other treatment (eg, depression)?

  7. Is the patient at risk for withdrawal symptoms? If so, what strategy is there to avoid them?

  8. Does the patient have an addictive personality, or is the patient seeking drugs?

  9. Is there a mechanism to assure appropriate use or to have appropriate follow-up?

Adapted from Hajak and Rodenbeck.54

Cognitive behavioural therapy is another alternative to or replacement for medication.55 In studies of the elderly, for example, meta-analysis has proposed that short-term treatment with hypnosedatives is more likely to cause adverse effects than to improve sleep.8 Other nonpharmacologic interventions are also likely to be successful.56 Managing insomnia should not consist solely of using prescription medication.

EDITOR’S KEY POINTS

  • Zopiclone is a hypnosedative drug commonly used to treat insomnia. Investigators have found substantial increases in its use in Canada.

  • While zopiclone is a highly effective sleep aid, there is controversy about the extent of its addiction potential.

  • When prescribing zopiclone, physicians should have the same concerns as they would for prescribing benzodiazepines.

POINTS DE REPÈRE DU RÉDACTEUR

  • L’hypnosédatif zopiclone est fréquemment utilisé contre l’insomnie. Certaines recherches indiquent que cet agent est de plus en plus utilisé au Canada.

  • La zopiclone est très ef_cace pour favoriser le sommeil, mais son potentiel d’accoutumance fait l’objet de controverse.

  • La prescription de zopiclone requiert les mêmes précautions que la prescription de benzodiazépines.

Footnotes

Competing interests

None declared

This article has been peer reviewed.

References

  • 1.Noble S, Langtry HD, Lamb HM. Zopiclone: an update of its pharmacology, clinical efficacy and tolerability in the treatment of insomnia. Drugs. 1998;55:277–302. doi: 10.2165/00003495-199855020-00015. [DOI] [PubMed] [Google Scholar]
  • 2.Kales A, Scharf MB, Kales JD, Soldatos CR. Rebound insomnia. A potential hazard following withdrawal of certain benzodiazepines. JAMA. 1979;241:1692–5. doi: 10.1001/jama.241.16.1692. [DOI] [PubMed] [Google Scholar]
  • 3.Sanger DJ. The pharmacology and mechanisms of action of new generation, non-benzodiazepine hypnotic agents. CNS Drugs. 2004;18(Suppl 1):9–15. doi: 10.2165/00023210-200418001-00004. [DOI] [PubMed] [Google Scholar]
  • 4.Hesse LM, von Moltke LL, Greenblatt DJ. Clinically important drug interactions with zopiclone, zolpidem and zaleplon. CNS Drugs. 2003;17:513–32. doi: 10.2165/00023210-200317070-00004. [DOI] [PubMed] [Google Scholar]
  • 5.Repchinsky C, editor. Canadian Pharmacists Association. Compendium of pharmaceuticals and specialties: the Canadian drug reference for health professionals. Ottawa, ON: Canadian Pharmacists Association; 2006. [Google Scholar]
  • 6.Chilcott LA, Shapiro CM. The socioeconomic impact of insomnia. An overview. Pharmacoeconomics. 1996;10(Suppl 1):1–14. doi: 10.2165/00019053-199600101-00003. [DOI] [PubMed] [Google Scholar]
  • 7.Busto UE, Sproule BA, Knight K, Herrmann N. Use of prescription and non-prescription hypnotics in a Canadian elderly population. Can J Clin Pharmacol. 2001;8:213–21. [PubMed] [Google Scholar]
  • 8.Glass J, Lanctôt KL, Herrmann N, Sproule BA, Busto UE. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 2005;331:1169. doi: 10.1136/bmj.38623.768588.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Rendle MA. Zopiclone (Imovane): evaluation in general practice. N Z Med J. 1990;103:225. [PubMed] [Google Scholar]
  • 10.Kassam A, Carter B, Patten SB. Sedative hypnotic use in Alberta. Can J Psychiatry. 2006;51:287–94. doi: 10.1177/070674370605100504. [DOI] [PubMed] [Google Scholar]
  • 11.Kassam A, Patten SB. Canadian trends in benzodiazepine and zopiclone use. Can J Clin Pharmacol. 2006;13:e121–7. [Google Scholar]
  • 12.Skinner BJ. Canada’s drug price paradox: the unexpected losses caused by government interference in pharmaceutical markets. Vancouver, BC: Fraser Institute Digital Publication; 2005. [Google Scholar]
  • 13.Bianchi M, Musch B. Zopiclone discontinuation: review of 25 studies assessing withdrawal and rebound phenomena. Int Clin Psychopharmacol. 1990;5(Suppl 2):139–45. [PubMed] [Google Scholar]
  • 14.Musch B, Maillard F. Zopiclone, the third generation hypnotic: a clinical overview. Int Clin Psychopharmacol. 1990;5(Suppl 2):147–58. [PubMed] [Google Scholar]
  • 15.Hajak G. A comparative assessment of the risks and benefits of zopiclone: a review of 15 years’ clinical experience. Drug Saf. 1999;21:457–69. doi: 10.2165/00002018-199921060-00003. [DOI] [PubMed] [Google Scholar]
  • 16.Delahaye C, Ferrand B, Pieddeloup C, Musch B. Post marketing surveillance of zopiclone: interim analysis on the first 10,000 cases in a clinical study in general practice. Int Clin Psychopharmacol. 1990;5(Suppl 2):131–8. [PubMed] [Google Scholar]
  • 17.Allain H, Delahaye C, Le Coz F, Blin P, Decombe R, Martinet JP. Postmarketing surveillance of zopiclone in insomnia: analysis of 20,513 cases. Sleep. 1991;14:408–13. doi: 10.1093/sleep/14.5.408. [DOI] [PubMed] [Google Scholar]
  • 18.Lader M. Rebound insomnia and newer hypnotics. Psychopharmacology. 1992;108:248–55. doi: 10.1007/BF02245108. [DOI] [PubMed] [Google Scholar]
  • 19.Lader M. Zopiclone: is there any dependence and abuse potential? J Neurol. 1997;244(4 Suppl 1):s18–22. doi: 10.1007/BF03160567. [DOI] [PubMed] [Google Scholar]
  • 20.Soyka M, Bottlender R, Möller HJ. Epidemiological evidence for a low abuse potential of zolpidem. Pharmacopsychiatry. 2000;33:138–41. doi: 10.1055/s-2000-11224. [DOI] [PubMed] [Google Scholar]
  • 21.Yanagita T. Dependence potential of zopiclone studied in monkeys. Pharmacology. 1983;27(Suppl 2):216–27. doi: 10.1159/000137930. [DOI] [PubMed] [Google Scholar]
  • 22.Clee WB, McBride AJ, Sullivan G. Warning about zopiclone misuse. Addiction. 1996;91:1389–90. doi: 10.1111/j.1360-0443.1996.tb03628.x. [DOI] [PubMed] [Google Scholar]
  • 23.Dündar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T. Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis. Hum Psychopharmacol. 2004;19:305–22. doi: 10.1002/hup.594. [DOI] [PubMed] [Google Scholar]
  • 24.Sutherland JC. Imovane and narcotic addiction. N Z Med J. 1991;104:103. [PubMed] [Google Scholar]
  • 25.Aranko K, Henriksson M, Hublin C, Seppäläinen AM. Misuse of zopiclone and convulsions during withdrawal. Pharmacopsychiatry. 1991;24:138–40. doi: 10.1055/s-2007-1014457. [DOI] [PubMed] [Google Scholar]
  • 26.Thakore J, Dinan TG. Physical dependence following zopiclone usage: a case report. Hum Psychopharmacol. 1992;7:143–5. [Google Scholar]
  • 27.Sullivan G, McBride AI, Clee WB. Zopiclone abuse in South Wales: three case reports. Hum Psychopharmacol. 1995;10:351–2. [Google Scholar]
  • 28.Jones IR, Sullivan G. Physical dependence on zopiclone: case reports. BMJ. 1998;316:117. doi: 10.1136/bmj.316.7125.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Sikdar S. Physical dependence on zopiclone. Prescribing this drug to addicts may give rise to iatrogenic drug misuse. BMJ. 1998;317:146. doi: 10.1136/bmj.317.7151.146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Ayonrinde O, Sampson E. Physical dependence on zopiclone. Risk of dependence may be greater in those with dependent personalities. BMJ. 1998;317:146. [PubMed] [Google Scholar]
  • 31.Flynn A, Cox D. Dependence on zopiclone [letter] Addiction. 2006;101:898. doi: 10.1111/j.1360-0443.2006.01448.x. [DOI] [PubMed] [Google Scholar]
  • 32.Sikdar S, Ruben SM. Zopiclone abuse among polydrug users. Addiction. 1996;91:285–6. [PubMed] [Google Scholar]
  • 33.Mamelak M, Scima A, Price V. Effects of zopiclone on the sleep of chronic insomniacs. Int Pharmacopsychiatry. 1982;17(Suppl 2):156–64. [PubMed] [Google Scholar]
  • 34.Dorian P, Sellers EM, Kaplan H, Hamilton C. Evaluation of zopiclone physical dependence liability in normal volunteers. Pharmacology. 1983;27(Suppl 2):228–34. doi: 10.1159/000137931. [DOI] [PubMed] [Google Scholar]
  • 35.Lader M, Denney SC. A double-blind study to establish the residual effects of zopiclone on performance in healthy volunteers. Pharmacology. 1983;27(Suppl 2):98–108. doi: 10.1159/000137916. [DOI] [PubMed] [Google Scholar]
  • 36.Bechelli LP, Navas F, Pierangelo SA. Comparison of the reinforcing properties of zopiclone and triazolam in former alcoholics. Pharmacology. 1983;27(Suppl 2):235–41. doi: 10.1159/000137932. [DOI] [PubMed] [Google Scholar]
  • 37.Boissl K, Dreyfus JF, Delmotte M. Studies on the dependence-inducing potential of zopiclone and triazolam. Pharmacology. 1983;27(Suppl 2):242–7. doi: 10.1159/000137933. [DOI] [PubMed] [Google Scholar]
  • 38.Lader M, Frcka G. Subjective effects during administration and on discontinuation of zopiclone and temazepam in normal subjects. Pharmacopsychiatry. 1987;20:67–71. doi: 10.1055/s-2007-1017078. [DOI] [PubMed] [Google Scholar]
  • 39.Fleming JA, McClure DJ, Mayes C, Phillips R, Bourgouin J. A comparison of the efficacy, safety and withdrawal effects of zopiclone and triazolam in the treatment of insomnia. Int Clin Psychopharmacol. 1990;5(Suppl 2):29–37. [PubMed] [Google Scholar]
  • 40.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 outpatients. Int Clin Psychopharmacol. 1990;5(Suppl 2):69–77. [PubMed] [Google Scholar]
  • 41.Ngen CC, Hassan R. A double-blind placebo-controlled trial of zopiclone 7.5 mg and temazepam 20 mg in insomnia. Int Clin Psychopharmacol. 1990;5(Suppl 2):165–71. doi: 10.1097/00004850-199007000-00001. [DOI] [PubMed] [Google Scholar]
  • 42.Pecknold J, Wilson R, le Morvan P. Long term efficacy and withdrawal of zopiclone: a sleep laboratory study. Int Clin Psychopharmacol. 1990;5(Suppl 2):57–67. [PubMed] [Google Scholar]
  • 43.Begg EJ, Robson RA, Frampton CM, Campbell JE. A comparison of efficacy and tolerance of the short acting sedatives midazolam and zopiclone. N Z Med J. 1992;105:428–9. [PubMed] [Google Scholar]
  • 44.Lemoine P, Allain H, Janus C, Sutet P. Gradual withdrawal of zopiclone (7.5 mg) and zolpidem (10 mg) in insomniacs treated for at least 3 months. Eur Psychiatry. 1995;10(Suppl 3):161–5. doi: 10.1016/0924-9338(96)80098-8. [DOI] [PubMed] [Google Scholar]
  • 45.Mann K, Bauer H, Hiemke C, Röschke J, Wetzel H, Benkert O. Acute, sub-chronic and discontinuation effects of zopiclone on sleep EEG and nocturnal melatonin secretion. Eur Neuropsychopharmacol. 1996;6:163–8. doi: 10.1016/0924-977x(96)00014-4. [DOI] [PubMed] [Google Scholar]
  • 46.Stip E, Furlan M, Lussier I, Bourgouin P, Elie R. Double-blind, placebo-controlled study comparing effects of zopiclone and temazepam on cognitive functioning of insomniacs. Hum Psychopharmacol. 1999;14:253–61. [Google Scholar]
  • 47.Voderholzer U, Riemann D, Hornyak M, Backhaus J, Feige B, Berger M, et al. A double-blind, randomized and placebo-controlled study on the polysomnographic withdrawal effects of zopiclone, zolpidem and triazolam in healthy subjects. Eur Arch Psychiatry Clin Neurosci. 2001;251:117–23. doi: 10.1007/s004060170045. [DOI] [PubMed] [Google Scholar]
  • 48.Tsutsui S Zolipidem Study Group. A double-blind comparative study of zolpidem versus zopiclone in the treatment of chronic primary insomnia. J Int Med Res. 2001;29:163–77. doi: 10.1177/147323000102900303. [DOI] [PubMed] [Google Scholar]
  • 49.Johansson BA, Berglund M, Hanson M, Pöhlén C, Persson I. Dependence on legal psychotropic drugs among alcoholics. Alcohol Alcohol. 2003;38:613–8. doi: 10.1093/alcalc/agg123. [DOI] [PubMed] [Google Scholar]
  • 50.Jaffe JH, Bloor R, Crome I, Carr M, Alam F, Simmons A, et al. A postmarketing study of relative abuse liability of hypnotic sedative drugs. Addiction. 2004;99:165–73. doi: 10.1111/j.1360-0443.2003.00631.x. [DOI] [PubMed] [Google Scholar]
  • 51.Mahomed R, Paton C, Lee E. Prescribing hypnotics in a mental health trust: what consultant psychiatrists say and what they do. Pharm J. 2002;268:657–9. [Google Scholar]
  • 52.Hajak G, Müller WE, Wittchen HU, Pittrow D, Kirch W. Abuse and dependence potential for the non-benzodiazepine hypnotics zolpidem and zopiclone: a review of case reports and epidemiological data. Addiction. 2003;98:1371–8. doi: 10.1046/j.1360-0443.2003.00491.x. [DOI] [PubMed] [Google Scholar]
  • 53.Medsafe Editorial Team. Dependence with zopiclone. Information for Health Professionals. Wellington, New Zealand: Medsafe. New Zealand Medicines and Medical Devices Safety Authority, Ministry of Health; 1998. [Accessed 2007 Oct 15]. Available from: www.medsafe.govt.nz/profs/PUarticles/3.htm. [Google Scholar]
  • 54.Hajak G, Rodenbeck A. Clinical management of patients with insomnia. The role of zopiclone. Pharmacoeconomics. 1996;10(Suppl 1):29–38. doi: 10.2165/00019053-199600101-00006. [DOI] [PubMed] [Google Scholar]
  • 55.Sivertsen B, Omvik S, Pallesen S, Bjorvatn B, Havik OE, Kvale G, et al. Cognitive behavioral therapy vs zopiclone for treatment of chronic primary insomnia in older adults: a randomized controlled trial. JAMA. 2006;295:2851–8. doi: 10.1001/jama.295.24.2851. [DOI] [PubMed] [Google Scholar]
  • 56.Morin CM, Culbert JP, Schwartz SM. Nonpharmacological interventions for insomnia: a meta-analysis of treatment efficacy. Am J Psychiatry. 1994;151:1172–80. doi: 10.1176/ajp.151.8.1172. [DOI] [PubMed] [Google Scholar]

Articles from Canadian Family Physician are provided here courtesy of College of Family Physicians of Canada

RESOURCES