Hostname: page-component-76fb5796d-2lccl Total loading time: 0 Render date: 2024-04-25T16:58:28.130Z Has data issue: false hasContentIssue false

General safety profile of zolpidem: safety in elderly, overdose and rebound effects

Published online by Cambridge University Press:  16 April 2020

H Allain
Affiliation:
Laborutoire de Pharmacologie Clinique, Centre Hospitalier Régional et Universitaire de Rennes, avenue du Pr-Léon-Bernard, 35043Rennes, France
J Monti
Affiliation:
Departamiento de Fannacología y Terapeutica, Facultad de Medicina, Hospital de Clinicas, 11600Montevideo, Uruguay
Get access

Summary

The different aspects of general safety of zolpidem are reviewed after analysing the safety data obtained in adults as well as in elderly patients. The low incidence of reported adverse events during the first three years of utilisation of zolpidem have corroborated the results of the clinical studies. The most frequent adverse effects are central nervous system (CNS) related but they can be largely prevented by respecting the recommended doses and prescription rules. In cases of acute overdoses, no severe complications have been attributed to zolpidem taken alone. In most of the studies carried out within the recommended treatment duration, abrupt treatment discontinuation was not associated with clinically significant rebound insomnia, and the available pre-clinical and clinical data indicate that the risk of abuse or dependence is minimal when prescribed according to the recommended doses of 10 mg in adults and 5 mg in elderly. Thus, with now well-established arguments on a large patient basis going in the same direction, the safety of zolpidem can authorise and justify its wide prescription in the short-term treatment of insomnia.

Type
Research Article
Copyright
Copyright © Elsevier, Paris 1997

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Agoumi, W, Guerault, E, Chaumet-Riffaud, A, Morselli, PEffect of abrupt discontinuation of zolpidem: a retrospective evaluation of pooled phase II and III european clinical studies In: Abstracts of the 11th European Congress of the European Sleep Research Society Helsinki, Finland, 5–10 July 1992 J Sleep Res 1 1992 521 suppl 1Google Scholar
Ahrens, J. Treating sleep disorders using zolpidem Therapiewoche 1993 43 38Google Scholar
APA, A task force report of the American Psychiatric Association on Benzodiazepine dependence toxicity and abuse Washington, DCAPA 1990Google Scholar
Armangaud, MH, Aubier, M, Pariente, Ret alEffets du zolpidem, du flunitrazépam et du triazolam sur les centres respiratoires et les gaz du sang artériel chez des patients porteurs d'une bronchopneumopathie chronique obstructive In: Abstract books, 10th Congress of the European Sleep Research Society Strasbourg, 20–25 May 1990 Adis 1990 165169Google Scholar
Aubier, M, Cramer, P, Murciano, D, Neveux, E. Comparison of the effects of zolpidem, triazolam and flunitrazepam on the respiratory regulatory centre activity in patients with chronic obstructive pulmonary disease (COPD) Biol Psychiatry 29 1991 333S701SGoogle Scholar
Baca, ECalidad de vida en el estudio de la electividad de los hipnóticos: experiencias con zolpidem Barcelona Sixth European Congress of the Association of European Psychiatrists 3–7 November 1992Google Scholar
Benoît, O, Bouard, G, Payan, C, Borderies, P, Prado, J. Effect of a single dose (10 mg) of zolpidem on visual and spectral analysis of sleep in young poor sleepers Psychopharmacology 116 1994 297303CrossRefGoogle Scholar
Besset, A, Tafti, M, Billiard, MEffects of zolpidem on sleep architecture and daytime psychomotor skills in poor sleepers Abstract books, 10th Congress of the European Sleep Research Society Strasbourg, 20–25 May 1990 Adis 1990 138Google Scholar
Biondi, F, Casadei, GLAbrupt shift to zolpidem 10 mg in insomniac patients previously taking benzodiazepine (BZD) — like hypnotics Athens 3rd International Congress of APPAC Developments in Psychiatry and Neurology of the Adult and the Child 2–5 December 1993Google Scholar
Biondi, F, Casadei, GL. Results of a multicentre trial with the hypnotic zolpidem in 1152 insomniac patients Curr Ther Res 55 3 1994 262274CrossRefGoogle Scholar
Borbèly, A, Youmbi-Balderer, G, Jaggi-Schwarz, KZolpidem (10 mg and 20 mg): hypnotic action and residual effects after a single bedtime doseSauvanet, JP, Lager, SZ, Morselli, PLImidazopyridines in sleep disorders: a novel experimental and therapeutic approach (LERS Monograph series vol. 6) 1988 Raven Press New York205210Google Scholar
Calanca, A, Dick, P. Efficacité du nouvel hypnotique zolpidem (Stilnox) en pratique ambulatoire (étude coopérative de praticiens de Genève, Lausanne et Tessin) Rev Méd Suisse Romande 111 1991 8588Google Scholar
Chaumet-Riffaud, A, Desforge, C, Lavoisy, J. Review of the post-marketing surveillance experience collected with zolpidem during the first three years after launch in Europe Abstracts of the 11th European Congress of the ESRS Finland 5–10 July 1992 J Sleep Res 1 1992 40 suppl 1Google Scholar
Ciapparelli, A, Colombo, C, Cuccato, G, Levi-Minzi, A, Lorizio, A. Shift to zolpidem, a new imidazopyridine hypnotic, in insomniac patients previously taking benzodiazepine hypnotics Minerva Psichiatr 32 1991 312Google Scholar
Cluydts, R, DeRoeck, J, Jolie, A. A three week multicentre general practitioner study of zolpidem in 651 patients with insomnia Acta Ther 19 1 1993 7391Google Scholar
Davenne, D, Meney, I, Mougin, Fet alPhysical performance the next afternoon of either an experimental sleep interruption or a night with zolpidemBook of abstracts WFSRS, Cannes, France, 21–25 Sept. 1991 Sleep Res 20A 1991 463Google Scholar
Depoortere, H, Zivkovic, B, Lloyd, Ket alZolpidem, a novel non-benzodiazepine hypnotic. I. Neuropharmacological and behavioral effects J Pharmacol Exp Therap 237 2 1986 649658Google Scholar
DeWit, H, Griffiths, R. Testing the abuse liability of anxiolytics and hypnotics drugs in humans Drug Alcohol Depend 28 1991 83111CrossRefGoogle Scholar
Emeriau, J, Descamps, A, Dechelotte, Pet alZolpidem and flunitrazepam: a multicenter trial in elderly hospitalised patientsSauvanet, JP, Lager, SZ, Morselli, PLImidazopyridines in sleep disorders: a novel experimental and therapeutic approach (LERS Monograph series vol. 6) 1988 Raven Press New York317326Google Scholar
Evans, SM, Funderburk, FR, Griffiths, RR. Zolpidem and triazolam in humans: behavioural and subjective effects and abuse liability J Pharmacol Exp Ther 255 1990 12461255Google ScholarPubMed
Fairweather, D, Kerre, J, Hindmarch, I. The effects of acute and repeated doses of zolpidem on subjective sleep, psychomotor performance and cognitive function in elderly volunteers Eur J Clin Pharmacol 43 1992 597601CrossRefGoogle ScholarPubMed
Garnier, R, Guerault, E, Muzard, Det alAcute zolpidem poisoning analysis of 344 cases Clin Toxicol 32 4 1994 391404Google ScholarPubMed
Ganzoni, E, Santoni, JP, Chevillard, V, Sebille, M, Mathy, BZolpidem in insomnia: a 3-year PMS study in Switzerland J Intern Med Res Copenhagen, Denmark, 1994 Preliminary results presented Assoc Eur Psychiatrists 1994 in pressGoogle Scholar
Godderis, J, Cluydts, R. Substitution from a benzodiazepine to zolpidem in elderly insomniacs: preliminary data Abstracts of the 11th European Congress of the ESRS Helsinki, Finland, 5–10 July 1992 Sleep Res 1 1992 83 suppl 1Google Scholar
Griffiths, R, Sannerud, C, Ator, N, Brady, J. Zolpidem behavioral pharmacology in baboons: self-injection, discrimination, tolerance and withdrawl J Pharmacol Exp Ther 260 3 1992 11991208Google Scholar
Guerault, E, Chaumet-Riffaud, A, Morselli, Pet alNeurological adverse event profile in the elderly with zolpidem 5 mg and 10 mg: a retrospective evaluation of European phase II and III studies Abstracts of the 11th European Congress of the ESRS Finland 5–10 July 1992 J Sleep Res 1 1992 89 suppl 1Google Scholar
Jonville, AP, Autret, E, Dutertre, JPet alIntoxications par les psychotropes et les toxiques Rev Med Tours 25 1991 6163Google Scholar
Kummer, J, Guendel, L, Kyrein, Het alSleep-EEG profile of elderly insomniacs during long-term treatment with zolpidemSauvanet, JP, Lager, SZ, Morselli, PLImidazopyridines in sleep disorders: a novel experimental and therapeutic approach (LERS Monograph series vol. 6) 1988 Raven Press New York381Google Scholar
Kurtz, D, Baas, V, Rumbach, LEffets de l'administration répétée de zolpidem 10 mg sur le sommeil et la vigilance diurne chez des mauvais dormeursAbstract book of the Symposium Stilnox1st Imidazopyridine. 10th Congress of the European Sleep Research Society Strasbourg, 20–25 May 1990 Adis 1991 143151Google Scholar
Lader, M. Rebound insomnia and newer hypnotics Psychopharmacology 108 1992 248255CrossRefGoogle ScholarPubMed
Lahmeyer, H, Docherty, J, Fillingim, Jet alThe effects of zolpidem in outpatients with chronic insomnia Sleep Res 19 1990 70Google Scholar
Langer, S, Arbilla, S. Limitations of the benzodiazepine receptor nomenclature: a proposal for a pharmalogical classification as omega receptor subtypes Fundam Clin Pharmacol 2 3 1988 159170CrossRefGoogle Scholar
Lheureux, P, Debailleul, G, DeWitte, O, Askenasi, R. Zolpidem intoxication mimicking narcotic overdose: response to flumazenil Hum Exp Toxicol 9 1990 105107CrossRefGoogle ScholarPubMed
Licciardello, L, Licini, P. Safety and efficacy of zolpidem therapy in sleep disorders: a multicenter trial in hospitalized patients Curr Ther Res Clin Exp 52 1992 652658CrossRefGoogle Scholar
Lorizio, A, Terzano, M, Parrino, LControlled study of the efficacy and safety of two oral doses of zolpidem (10 and 20 mg)Sauvanet, JP, Lager, SZ, Morselli, PLImidazopyridines in sleep disorders: a novel experimental and therapeutic approach (LERS Monograph series vol. 6) 1988 Raven Press New York385Google Scholar
Maarek, L, Cramer, P, Attali, Pet alThe safety and efficacy of zolpidem in insomniac patients: a long-term open study in general practice J Int Med Res 20 1992 162170CrossRefGoogle ScholarPubMed
Maggioni, M, Frattola, LDouble-blind controlled study of the efficacy and safety of zolpidem versus flunitrazepamSauvanet, JP, Lager, SZ, Morselli, PLImidazopyridines in sleep disorders: a novel experimental and therapeutic approach (LERS Monograph series vol. 6) 1988 Raven Press New York386387Google Scholar
Maillard, D, Thiercelin, JF, Fuseau, Eet alEffects of zolpidem versus diazepam and placebo on breathing control parameters in healthy human subjects and heavy snoorers Int J Clin Pharm Res 12 1992 2735Google Scholar
Merlotti, L, Roehrs, T, Koshorek, Get alThe dose effects of zolpidem on the sleep of healthy normals J Clin Psychopharmacol 9 1989 914CrossRefGoogle ScholarPubMed
Monti, J. Effect of zolpidem on sleep in insomniac patients Eur J Clin Pharmacol 36 1989 461466CrossRefGoogle ScholarPubMed
Monti, JM, Attali, P, Monti, D, Zipfel, A, De la Giclais, B, Morselli, PL. Zolpidem and rebound insomnia. A double-blind, controlled polysomnographic study in chronic insomniac patients Pharmacopsychiatria 27 1994 166175CrossRefGoogle ScholarPubMed
Murciano, D, Moreau, J, Barthouil, P, Auber, M. Long term effects of zolpidem (Z) on arterial blood gases and control of breathing in patients with severe chronic obstructive pulmonary disease (COPD) Abstracts of the International Conference of the American Lung Association and the American Thoracic Society Miami Beach, Florida, USA 17–20 May 1992 Am Rev Respir Dis 145 1992 A636Google Scholar
Ochs, R, Fillingis, J, Cutler, Met alThe effect of zolpidem in elderly patients with chronic insomnia Abstracts of the 11th European Congress of the European Sleep Research Society Helsinki, Finland, 5–10 July 1992 J Sleep Res 1 1992 164 suppl 1Google Scholar
Pagot, R, Cramer, P, L'Heritier, Cet alComparison of the efficacy and tolerability of zolpidem 20 mg and triazolam 0.5 mg in anxious or depressed insomniac patients Curr Ther Res 53 1993 8897CrossRefGoogle Scholar
Paty, J, Barthouil, PEfficacy and tolerance of a shift from benzodiazepine hypnotic drugs to zolpidem 10 mg/day in chronic insomniacs: an open study based on general practitionersCannes, FranceAbstacts of the WFSRS 21–25 September 1991Google Scholar
Pélissolo, A, Bisserbe, JC. Benzodiazepine dependence: clinical as-pects and biological perspectives Encéphale 20 1994 147157Google Scholar
Perrault, G, Morel, E, Sanger, D, Zivkovic, B. Differences in pharmacological profiles of a new generation of benzodiazepine and non-benzodiazepine hypnotics Eur J Pharmacol 187 3 1990 487494CrossRefGoogle ScholarPubMed
Perrault, G, Morel, E, Sanger, D, Zivkovic, B. Lack of tolerance and pysical dependence upon repeated treatment with the novel hypnotic zolpidem J Pharmacol Exp Therap 263 1 1992 298303Google Scholar
Quera-Salva, T, Borderies, P, Moreau, J, Cugy, D. The efficacy of zolpidem during and after a progressive shift from benzodiazepine hypnotics in elderly chronic insomniac patients J Sleep Res 1 suppl 1 1992 187Google Scholar
Rhodes, S, Parry, P, Hanning, C. A comparison of the effects of zolpidem and placebo on respiration and oxygen saturation during sleep in healthy elderly Br J Clin Pharmacol 30 1990 817824CrossRefGoogle ScholarPubMed
Richens, A, Mercer, AJ, Jones, DM, Griffiths, A, Marshall, RW. Effects of zolpidem on saccadic eye movements and psychomotor performance: a double-blind, placebo controlled study in healthy volunteers Br J Clin Pharmacol 36 1993 6165CrossRefGoogle ScholarPubMed
Roehrs, TA, Roth, T, Scharf, Met alRebound insomnia potential of zolpidem 10 mg as evaluated by three different methods Association of the Professional Sleep Societies Annual Meeting 1992 134Google Scholar
Roger, M, Attali, P, Nicaise, Jet alEfficacy of 5 mg and 10 mg zolpidem in the elderly: a double-blind study versus 0.25 mg triazolam Abstracts of the 5th World Congress of Biological Psychiatry Florence, Italy, 10–14 June 1991 Br J Psychiatry 19 1991 521S suppl 11Google Scholar
Roger, M, Attali, P, Coquelin, J. Multicenter, double-blind, controlled comparison of zolpidem and triazolam in elderly patients with insomnia Clin Ther 15 1993 127135Google ScholarPubMed
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 31 7 1992 693700CrossRefGoogle Scholar
Sauvanet, JP, Maarek, L, Roger, Met alOpen long-term trials with zolpidem in insomniaSauvanet, JP, Lager, SZ, Morselli, PLImidazopyridines in sleep disorders: a novel experimental and therapeutic approach (LERS Monograph series vol. 6) 1988 Raven Press New York339349Google Scholar
Scharf, MB, Mayleben, DW, Kaffeman, Met alDose response effects of zolpidem in normal geriatric subjects J Clin Psychiatry 52 1991 7783Google ScholarPubMed
Scharf, MB, Vogel, G, Kaffeman, M, Ochs, RF. Dose-response of zolpidem in elderly patients with chronic insomnia Sleep Res 20 1991 84Google Scholar
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 271279CrossRefGoogle ScholarPubMed
Shaw, S, Curson, H, Coquelin, J. A double-blind, comparative study of zolpidem and placebo in the treatment of insomnia in elderly psychiatric in-patients J Int Med Res 1992 20 150161CrossRefGoogle ScholarPubMed
Steens, RD, Pouliot, Z, Millar, TW, Kryger, MH, George, CF. Effects of zolpidem and triazolam on sleep and respiration in mild to moderate chronic obstructive pulmonary disease Sleep 1993 16 318326CrossRefGoogle ScholarPubMed
Tracqui, A, Kintz, P, Mangin, P. A fatality involving two unusual compounds — zolpidem and acepromazine Am J Forensic Med Pathol 14 1993 309312CrossRefGoogle ScholarPubMed
Wheatley, DZolpidem and placebo: a study in general practice in patients suffering from insomniaSauvanet, JP, Lager, SZ, Morselli, PLImidazopyridines in sleep disorders: a novel experimental and therapeutic approach (LERS Monograph series vol. 6) New YorkRaven Press 1988 305316Google Scholar
World Psychiatric Association, Task Force on sedative hypnotics Eur Psychiatry 1993 8 4549CrossRefGoogle Scholar
Submit a response

Comments

No Comments have been published for this article.