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Pharmacopsychiatry 2000; 33(4): 138-141
DOI: 10.1055/s-2000-11224
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Epidemiological Evidence for a Low Abuse Potential of Zolpidem

M. Soyka, R. Bottlender, H.-J. Möller
  • Psychiatric Hospital, University of Munich, Munich, Germany
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Publication History

Publication Date:
31 December 2000 (online)

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The abuse risk of new non-benzodiazepine hypnotics such as zolpidem has been discussed in a number of recent publications. We performed a Medline analysis which showed that, to date, 15 cases of abuse or dependence have been published. In 6 patients, the abuse was secondary to other forms of abuse or dependence. Other data from medical statistics and pharmacoepidemiological studies suggest the abuse potential of zolpidem to be much lower than that of other hypnotics. We conclude that zolpidem is a relatively safe drug compared to conventional hypnotics. Patients with other substance abuse histories may be considered as risk patients for later abuse of zolpidem.

References

  • 1 Allain H, Monti J. General safety profile of zolpidem: Safety in elderly, overdose and rebound effects.  European Psychiatry. 1997;  12 ((Suppl. 1)) 21-29
    PubMedGoogle Scholar
  • 2 Annseau M, Pitchot W, Hansenne M. et al . Psychotic reactions to zolpidem.  Lancet. 1992;  339 809
    PubMedGoogle Scholar
  • 3 Arzneimittelkommission der deutschen Ärzteschaft . Keine Verordnung von Zolpidem bei bekannter Benzodiazepinabhängigkeit.  Dt Ärzteblatt. 1999;  96 B-500
    PubMedGoogle Scholar
  • 4 Besset A, Tafti M, Biliard M. Effects of zolpidem on sleep architecture and daytime psychomotor skills in poor sleepers. In: Abstract books, 10th congress of the European Sleep Research Society, Strasbourg, Adis 20 - 25 May 1990: 138
    Google Scholar
  • 5 Borbe`ly A, Youmbi-Balderer G, Jaggi-Schwarz K. Zolpidem (10 mg and 20 mg): hypnotic action and residual effects after a single bedtime dose. In: Sauvanet JP, Lager SZ, Morselli PL, eds. Imidazopyridines in sleep disorders: a novel experimental and therapeutic approach.  LERS Monograph series, New York: Raven Press . 1988;  6 205-210
    PubMedGoogle Scholar
  • 6 Bottlender R, Schütz C, Möller H J, Soyka M. Zolpidem Dependence in a Patient with Former Polysubstance Abuse.  Pharmacopsychiat.. 1997;  30 108
    PubMedGoogle Scholar
  • 7 Bruun T G. Misbrugspotentiale under brug og abstinenspsykose efter behandling med sovemidlet zolpidem (Stilnoct).  Ugeskr Laeger. 1993;  155 2711-2712
    PubMedGoogle Scholar
  • 8 Cavallaro R, Regazetti M G, Smeraldi E. Tolerance and withdrawal with zolpidem.  Lancet. 1992;  342 374-375
    PubMedGoogle Scholar
  • 9 Chamorro-Garcia L, Martin M, De-Dios-Molina J. Zolpidem dependence.  Med. Clin.. 1996;  106/12 478-479
    PubMedGoogle Scholar
  • 10 Clarenbach P. Neue Schlafmittel: Zopiclon und Zolpidem.  Arzneimitteltherapie. 1996;  23 82-87
    PubMedGoogle Scholar
  • 11 Depoortere H, Zivkovic B, Lloyd K. et al . Zolpidem, a novel non-benzodiazepine hypnotic. I. Neuropharmacological and behavioral effects.  J. Pharmacol. Exp. Ther.. 1986;  237 (2) 649-658
    PubMedGoogle Scholar
  • 12 Depoortere H, Zivkovic B, Lloyd K G, Sanger J, Perrault G, Langer S Z, Bartholini G. Zolpidem, a novel nonbenzodiazepine hypnotic, I. Neuropharmacological and behavioral effects.  J. Pharmacol. Exp. Ther.. 1986;  237 649-658
    PubMedGoogle Scholar
  • 13 Dujardin K, Guieu J D, Leconte-Lambert C, Leconte P, Borderies P, de La Giclais B. Comparison of the Effects of Zolpidem and Flunitrazepam on Sleep Structure and Daytime Cognitive Functions.  Pharmacopsychiat.. 1998;  31 14-18
    PubMedGoogle Scholar
  • 14 Evans S M, Funderburk F R, Griffiths R R. Zolpidem and triazolam in humans: behavioral and subjective effects and abuse liability.  J. Pharmacol. Exp. Ther.. 1990;  255 (3) 1246-1255
    PubMedGoogle Scholar
  • 15 Gericke C A, Ludolph A C. Chronic abuse of zolpidem.  JAMA. 1994;  22 272
    PubMedGoogle Scholar
  • 16 Glaeske G. Psychotrope und andere Arzneimittel mit Mißbrauchs- und Abhängigkeitspotential.  In: DHS (ed). Jahrbuch Sucht, Geestacht: Neuland. 1996;  97 32-54
    PubMedGoogle Scholar
  • 17 Griffiths R R, Sannerud C A, Ator N, Brady J V. Zolpidem behavioral pharmacology in baboons: self-injection, discrimination, tolerance and withdrawal.  J. Pharmacol. Exp. Ther.. 1992;  260 1199-1208
    PubMedGoogle Scholar
  • 18 Guazelli M, Ciapparelli A, Balsamo E L. et al. . Terapia dell'insomnia correlata con i disturbi depressivi. Studio in doppio cieco sugli effetti della somministrazione e della sospensione die zolpidem versus flunitrazepam in pazienti depressi insonni.  Minerva Psichiatria. 1993;  34 193-203
    PubMedGoogle Scholar
  • 19 Hofmann M, Eichhorn M. Ungestilltes Verlangen: Abhangigkeitssyndrom von Zolpidem (Stilnox).  Psychiatr-Prax.. 1998 Nov.;  25 (6) 313
    PubMedGoogle Scholar
  • 20 Iruela L M, Ibanez-Rojo V, Baca E. More on Zolpidem side effects. Lancet 1993a: 1495-1496
    Google Scholar
  • 21 Iruela L M, Ibanez-Rojo V, Baca E. Zolpidem-induced macropsia in anorexic woman. Lancet 1993b: 443-444
    Google Scholar
  • 22 Keup W. Zolpidem and Zopiclon. Geringeres Mißbrauchspotential im Vergleich mit Benzodiazepin-Hypnotika.  Arzneimitteltherapie. 1999;  16 246-253
    PubMedGoogle Scholar
  • 23 Keup W. Mißbrauchsmuster bei Abhängigkeit von Alkohol, Medikamenten und Drogen. Frühwarnsystem-Daten für die Bundesrepublik Deutschland 1976 - 1990. Lambertus Verlag, Freiburg 1993
    Google Scholar
  • 24 Kurtz D, Baas V, Rumbach L. Effects de l'administration répétée de zolpidem 10 mg sur le sommeil et la vigilance diurne chez des mauvais dormeurs. In: Abstract book of the Symposium Stilnox1st Imidazopyridine.  10th Congress of the European Sleep Research Society. Straßbourg. 1990;  20-25 May 1990 143-151
    PubMedGoogle Scholar
  • 25 Lader M, Russel L. Guidelines for the prevention and treatment of benzodiazepine dependence: summary of a report from the Mental Health Foundation.  Addiction. 1993;  88 1707-1708
    PubMedGoogle Scholar
  • 26 Lader M. Rebound insomnia and newer hypnotics.  Psychopharmacology. 1992;  108 248-255
    PubMedGoogle Scholar
  • 27 Lader M. Zopiclone: Is there any dependence and abuse potential?.  J. Neurol.. 1997;  244 (Suppl. 1) 18-22
    PubMedGoogle Scholar
  • 28 Langer S, Arbilla S. Limitations of the benzodiazepine receptor nomenclature: a proposal for a pharmacological classification as omega receptor subtypes.  Fundam. Clin. Pharmacol.. 1988;  2 (3) 159-170
    PubMedGoogle Scholar
  • 29 Lemoine P, Allain H, Janus C. et al . 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) 161s-165s
    CrossrefPubMedGoogle Scholar
  • 30 Lorizio A, Terzano M, Parrino L. Controlled study of efficacy and safety of two oral doses of zolpidem ( 10 and 20 mg). In: Sauvanet JP, Lager SZ, Morselli PL, eds. Imidazopyridines in sleep disorders: a novel experimental and therapeutic approach.  LERS Monograph series. New York: Raven Press. 1988;  6 385
    PubMedGoogle Scholar
  • 31 Maarek L, Cramer P, Attalo P. et al . The safety and efficicacy of zolpidem in insomniac patients: a long-term open study in general practice.  J. Int. Med. Res.. 1992;  20 162-170
    PubMedGoogle Scholar
  • 32 Maggioni M, Frattola L. Double-blind controlled study of the efficacy and safety of zolpidem versus flunitrazepam. In: Sauvanet JP, Lager SZ, Morselli PL, eds. Imidazopyridines in sleep disorders: a novel experimental and therapeutic approach.  LERS Monograph series. New York: Raven Press . 1988;  6 386-387
    PubMedGoogle Scholar
  • 33 Merlotti L, Roehrs T, Koshorek G. et al . The dose effects of zolpidem on the sleep of healthy normals.  J. Clin. Psychopharmacol.. 1989;  9 9-14
    PubMedGoogle Scholar
  • 34 Monti J. Effect of zolpidem on sleep in insomniac patients.  Eur. J. Clin. Pharmacol.. 1989;  36 461-466
    CrossrefPubMedGoogle Scholar
  • 35 Monti J M, Attali P, Monti D, Zipfel A, De la Giclais B, Morselli P L. Zolpidem and rebound insomnia. A double-blind, controlled polysomnographic study in chronic insomniac patients.  Pharmacopsychiatria. 1994;  27 166-175
    PubMedGoogle Scholar
  • 36 Morselli P L. Zolpidem side effects. Lancet 1993: 868-869
    Google Scholar
  • 37 Müller W E. Wie „neu” sind die Hypnotika Zopiclon und Zolpidem?.  Arzneiverordnung in der Praxis. 1994;  2 6-8
    PubMedGoogle Scholar
  • 38 Pagot R, Cramer P, L'Heritier C. et al . Comparison of the efficacy and tolerability of zolpidem 20 mg and triazolam 0.5 mg in anxious or depressed insomniac patients.  Curr. Ther. Res.. 1993;  53 88-97
    CrossrefPubMedGoogle Scholar
  • 39 Perrault G, Morel E, Sanger D, Zivokovic B. Differences in pharmacological profiles of a new generation of benzodiazepine and non-benzodiazepine hypnotics.  Eur. J. Pharmacol.. 1990;  187 (3) 487-494
    CrossrefPubMedGoogle Scholar
  • 40 Perrault G, Morel E, Sanger D J, Zivkovic B. Lack of tolerance and physical dependence upon repeated treatment with the novel hypnotic zolpidem.  J. Pharmacol. Exp. Ther. 1992;  263 ((1)) 298-303
    PubMedGoogle Scholar
  • 41 Ravishankar A, Carnwath T. Zolpidem tolerance and dependence - two case reports.  J. Psychopharmacology. 1998;  12 103-104
    PubMedGoogle Scholar
  • 42 Richens A, Mercer A J, Jones D M, Griffiths A, Marshall R W. Effects of zolpidem on saccadic eye movements and psychomotor performance: a double-blind, placebo cotrolled study in healthy volunteers.  Br. J. Clin. Pharmacol. 1993; 
    PubMedGoogle Scholar
  • 43 Roehrs T A, Roth T, Scharf M. et al .Rebound insomnia potential of zolpidem 10 mg as evaluated by three different methods (Abstract). Presented at: Association of Professional Sleep Societies Annual Meeting, Phoenix, Arizona, USA 29 May - 3 June 1992: 134
    Google Scholar
  • 44 Sakkas P, Psarros C, Masdrakis V, Liappas J, Christodoulou G N. Dependence on zolpidem: a case report.  Eur. Psychiatry. 1999;  Oct, 14 (6) 358-359
    PubMedGoogle Scholar
  • 45 Sanchez L G, Sanchez J M, Lopez-Moreno J. Dependence and tolerance with zolpidem (letter).  Am. J. Health Syst. Pharm.. 1996;  53 (21) 26-38
    PubMedGoogle Scholar
  • 46 Sanger D, Zivkovic B. Differential development of tolerance to the depressant effects of benzodiazepine and non-benzodiazepine agonists at the omega modulatory sites of GABA A receptors.  Neuropharmacology. 1992;  31 (7) 693-700
    CrossrefPubMedGoogle Scholar
  • 47 Sanger D J, Zivkovic B. Discriminative stimulus properties of chlordiazepoxide and zolpidem. Agonist and antagonist effects of CGS 9896 and ZK 91296.  Neuropharmacol.. 1987;  26 499-595
    CrossrefPubMedGoogle Scholar
  • 48 Sanger D J, Zivkovic B. The discriminative stimulus properties of zolpidem, a novel imidazopyridine hypnotic.  Psychopharmacol.. 1986;  89 317-322
    PubMedGoogle Scholar
  • 49 Sakkas P, Psarros C, Masdrakis V, Liappas J, Christodoulou G N. Dependence on zolpidem: case report.  Eur. Psychiatry. 1999;  14 358-359
    CrossrefPubMedGoogle Scholar
  • 50 Sauvanet J P, Maarek L, Roger M, Renaudin J, Luovel E, Orafiamma B. Open long-term trials with zolpidem in insomnia. In: Sauvanet JP, Lager SZ, Morselli PL, eds. Imidazopyridines in sleep disorders: a novel experimental and therapeutic approach.  (LERS Monograph series; vol. 6). New York: Raven Press. 1988;  6 339-349
    PubMedGoogle Scholar
  • 51 Sauvanet J P, Maarek L, Roger M. Open long-term trials with zolpidem in insomnia. In: Sauvanet JP, Langer SZ, Morselli PL (ed.): Imidazopyridines in Sleep Disorders. New York: Raven Press. 1988: 339-349
    Google Scholar
  • 52 Schadeck B, Chelly M, Amsellem D. et al. . Efficacité comparative de la doxylamine (15 mg) et du zolpidem (10 mg) dans le traitement de l'insomnie commune.  Sem. Hop.. 1996;  72 428-439
    PubMedGoogle Scholar
  • 53 Scharf M B, Vogel G, Kaffeman M, Ochs R F. Dose-response of zolpidem in elderly patients with chronic insomnia.  Sleep Res.. 1991b;  20 84
    PubMedGoogle Scholar
  • 54 Schlich D, L'Heritier C, Coquelin J, Attali P. Long-term treatment of insomnia with zolpidem: a multicentre general practitioner study of 107 patients.  J. Int. Med. Res.. 1991;  19 271-279
    PubMedGoogle Scholar
  • 55 Ströhle A, Antonijevic I A, Steiger A, Sonntag A. Dependency of non-benzodiazepine hypnotics. Two case reports.  Nervenarzt. 1999;  70, 1 72-75
    CrossrefPubMedGoogle Scholar
  • 56 Thome J, Ruchsow M, Rössler M. et al . Zolpidem-Abhängigkeit und Depression im Senium.  Psychiatr. Prax.. 1995;  22 165-166
    PubMedGoogle Scholar
  • 57 Vogel G, Poirrier R. Studies of effects following discontinuation of zolpidem treatment. In: Freeman H, Puech AJ, Roth T (eds) Zolpidem: an update of its pharmacological properties and therapeutic place in the management of insomnia. Amsterdam Oxford: Elsevier 1996: 149-160
    Google Scholar
  • 58 Weerts E M, Griffiths R R. Zolpidem self-injection with concurrent physical dependence under conditions of long-term continuous availability in baboons.  Behav-pharmacol.. 1998;  9 (3) 285-297
    PubMedGoogle Scholar
  • 59 Wheatley D. Prescribing short-acting hypnosedatives. Current recommendations from a safety perspective.  Drug Safety. 1992;  7 (2) 106-115
    PubMedGoogle Scholar

1 Glaeske model, definition of long-term users; patients who continue to use a drug for more than 90 days following the first prescription.

2 AOK model (AOK refers to the „Allgemeine Ortskrankenkassen”, a major public health insurance in Germany), definition of long-term users: patients who in each of the 4 quarters following the first prescription still take at least half of a DDD.

Dr. med. M. Soyka

Psychiatrisches Krankenhaus, Universität München

Nussbaumstraße 7

80336 Munich

Germany

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