Summary
Abstract
Zolpidem (Ambien®, Stilnox®, Myslee®), an imidazopyridine, is a nonbenzodiazepine hypnotic indicated for the short-term treatment of insomnia.
Zolpidem improves sleep in patients with insomnia. Its overall tolerability is favourable when administered according to the manufacturer’s prescribing information, with a low propensity to cause clinical residual effects, withdrawal, dependence or tolerance. In addition, most evidence suggests that the drug is associated with minimal rebound insomnia. In the only clinical trials that investigated the use of a hypnosedative drug in an ‘as-needed’ regimen, zolpidem produced a global improvement in sleep. Thus, zolpidem continues to be a useful therapeutic option in the pharmacological treatment of patients with insomnia.
Pharmacological Properties
Zolpidem, an imidazopyridine, is a GABAa agonist, with selective binding affinity for the benzodiazepine ω1 receptor. In general, zolpidem does not alter sleep architecture.
There were no significant next-day (i.e. >8 hours post-dose) clinical residual effects of zolpidem versus placebo in patients with insomnia in trials that used psychomotor or memory tests. In addition, differences in next-day effects on psychomotor function in patients with insomnia significantly favoured zolpidem 10mg versus zopiclone 7.5mg, flurazepam 30mg or flunitrazepam 1mg recipients.
Although psychomotor function was generally significantly impaired with zolpidem versus placebo ≤7 hours post-dose (i.e. during the night) in healthy volunteers (including some aged 64–79 years), these effects were absent the next day (from about 8 hours post-dose). There was generally no significant memory impairment with zolpidem relative to placebo, from about 8 hours post-dose. However, in one trial, anterograde amnesia was reported in zolpidem or triazolam recipients, but not zaleplon recipients. Some, but not all, studies found a significant effect of zolpidem on memory during the night (≤7 hours post-dose). However, the impairment was less severe than that with zopiclone.
Zolpidem 10mg is absorbed rapidly; the mean time to maximum plasma concentration is 1.4 hours (with a single dose), and the absolute oral bioavailability of the drug is ≈70%.
The drug is almost entirely protein bound in the plasma (92%). Although zolpidem is metabolised extensively, all three metabolites are inactive. Elimination is also rapid, with a mean terminal elimination half-life of 2.1 hours for a single dose of zolpidem 10mg.
Dosage adjustment is recommended for patients with hepatic impairment and in the elderly, since the mean maximum plasma concentration and area under the plasma concentration-time curve are increased in these patient groups. Dosage adjustment of zolpidem may also be required when coadministered with CNS-depressant drugs as these agents may enhance the CNS effects of any hypnosedative drug, including zolpidem.
Therapeutic Efficacy
Zolpidem is an effective hypnotic when used in a continuous regimen in adult and elderly patients with insomnia in trials of up to 5 weeks’ duration, and in trials of up to 12 weeks’ duration in adult patients with insomnia when used in ‘as-needed’ or intermittent regimens. Zolpidem 10 mg/day was at least as effective as trazodone 50 mg/day, was not inferior to zopiclone 7.5 mg/day and had broadly similar efficacy to doxylamine 15 mg/day, triazolam 0.25 or 0.5 mg/day, flunitrazepam 1 mg/day, or nitrazepam 5 mg/day (in trials in adult patients). Similarly, the efficacy of zolpidem 5 mg/day was not significantly different from that of triazolam 0.125 or 0.25 mg/day, or temazepam 15 mg/day in trials in elderly patients but was superior to zaleplon 5 mg/day for total sleep time.
Zolpidem 10 mg/day is effective when used on an ‘as-needed’ basis in patients with insomnia according to global efficacy ratings, although results across studies for sleep parameters are mixed. In three placebo-controlled trials of 4–12 weeks’ active treatment duration in patients with primary insomnia, subjective global ratings of efficacy were better in zolpidem than in placebo recipients. Total sleep time was improved versus placebo in two of these trials. In general, there was no significant difference between treatment groups for most other sleep parameters, and where differences were observed these were not consistent across studies. A placebo effect was evident in one trial. The equivalence of the intermittent and continuous zolpidem administration regimens was not established in two 2-week trials in patients with insomnia. In two noncomparative 3-week trials in a primary care setting, a total of >4000 patients with insomnia took zolpidem 10 mg/day ‘asneeded’. About 80% or 90% of patients experienced an improvement according to the Clinical Global Impression–Improvement scale in each trial.
Tolerance is unlikely with continuous or intermittent use of zolpidem.
Tolerability
Zolpidem is generally well tolerated, including in elderly patients. Serious adverse events are rare. The nature of adverse events with zolpidem was broadly similar to that of nonbenzodiazepines (e.g. zopiclone) and benzodiazepines (e.g. triazolam, nitrazepam).
Next-day residual effects evident from post-sleep efficacy assessments were not significantly different with zolpidem from those observed in doxylamine, trazodone, nitrazepam or triazolam recipients.
In comparative trials in patients with insomnia, which assessed rebound insomnia as a primary endpoint, zolpidem recipients did not experience significant rebound insomnia, unlike triazolam recipients. The incidence of rebound insomnia with zolpidem was similar to that with temazepam, less frequent than with zopiclone and more frequent than that with placebo. In other studies that included an evaluation of rebound insomnia, most found no evidence for this withdrawal reaction in patients with insomnia.
There are case reports of abuse, dependence or withdrawal syndrome, but in the majority of these cases, the recommended dose of zolpidem was exceeded and most patients had a history of substance abuse and/or a psychiatric disorder.
On the basis of available evidence, the tolerability profile of zolpidem 10 mg/ day used ‘as needed’ appears broadly similar to that of continuous use of the drug. There is a low potential for rebound insomnia with ‘as-needed’ use, according to data from two placebo-controlled trials. Dependence is not likely to occur, since ‘as-needed’ use was generally not associated with drug-seeking behaviour.
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Notes
Also registered as Niotal®, Nitrest®, Somnil®, Somno®, Stilnoct®, Supedal®. The use of trade names is for product identification purposes only and does not imply endorsement.
References
Holm KJ, Goa KL. Zolpidem: an update of its pharmacology, therapeutic efficacy and tolerability in the treatment of insomnia. Drugs 2000 Apr; 59(4): 865–89
Langtry HD, Benfield P. Zolpidem: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential. Drugs 1990; 40(2): 291–313
Nakajima T, Sasaki T, Nakagome K, et al. Comparison of the effects of zolpidem and zopiclone on nocturnal sleep and sleep latency in the morning: a cross-over study in healthy young volunteers. Life Sci 2000 May 26; 67(1): 81–90
Terzano MG, Parrino L, Smerieri A, et al. Modifications of sleep parameters under an intermittent treatment regimen with zolpidem [abstract no. 0727.L]. Sleep 2003; 26 Suppl.: A289
Quera-Salva MA, McCann C, Boudet J, et al. Effects of zolpidem on sleep architecture, night time ventilation, daytime vigilance and performance in heavy snorers. Br J Clin Pharmacol 1994; 37(6): 539–43
Cirignotta F, Mondini S, Zucconi M, et al. Controlled polysomnographic study of the effects of benzodiazepine and non-benzodiazepine hypnotics (zolpidem) in obstructive sleep apnea patients: preliminary results. In: Sauvanet JP, Langer SZ, Morselli PL, editors. Imidazopyridines in sleep disorders. New York: Raven Press, 1988: 297–304
Lippmann S, Mazour I, Shahab H. Insomnia: therapeutic approach. South Med J 2001 Sep; 94(9): 866–73
Roth T, Hajak G, Ustun TB. Consensus for the pharmacological management of insomnia in the new millennium. Int J Clin Pract 2001 Jan–Feb 28; 55(1): 42–52
Sanofi-Synthelabo Inc. Ambien® zolpidem tartrate: prescribing information [online]. Available from URL: http://www.sanofisynthelabous.com/products/pi_ambien/pi_ambien.html [Accessed 2004 Feb 3]
Fujisawa. Myslee® Tablets 5mg 10mg: prescribing information. Fujisawa, 2004 May
Sanofi Synthelabo. Stilnoct 5mg, Stilnoct 10mg summary of product characteristics [online]. Available from URL: http://emc.medicines.org.uk [Accessed 2004 May 27]
Vermeeren A. Residual effects of hypnotics: epidemiology and clinical implications. CNS Drugs 2004; 18(5): 297–328
Terzano MG, Rossi M, Palomba V, et al. New drugs for insomnia: comparative tolerability of zopiclone, zolpidem and zaleplon. Drug Saf 2003; 26(4): 261–82
Verster JC, Volkerts ER, Schreuder AHCML, et al. Residual effects of middle-of-the-night administration of zaleplon and zolpidem on driving ability, memory functions, and psychomotor performance. J Clin Psychopharmacol 2002; 22(6): 576–83
Vermeeren A, O’Hanlon JF, Declerck AC, et al. Acute effects of zolpidem and flunitrazepam on sleep, memory and driving performance, compared to those of partial sleep deprivation and placebo. Acta Ther 1995; 21(1): 47–64
Fleming J, Moldofsky H, Walsh JK, et al. Comparison of the residual effects and efficacy of short term zolpidem, flurazepam and placebo in patients with chronic insomnia. Clin Drug Invest 1995; 9(6): 303–13
Ertle S, Arnal MA, Macher JP, et al. Acute bedtime administration of zolpidem does not induce residual daytime driving impairment compared to zopiclone in primary insomniac subjects: preliminary results in 16 patients [abstract no. 0188.C]. Sleep 2003; 26 Suppl.: A77
Dujardin K, Guieu JD, Leconte-Lambert C, et al. Comparison of the effects of zolpidem and flunitrazepam on sleep structure and daytime cognitive functions: a study of untreated unsomniacs. Pharmacopsychiatry 1998; 31(1): 14–8
Uchiumi M, Isawa S, Suzuki M, et al. The effects of zolpidem and zopiclone on daytime sleepiness and psychomotor performance. Nihon Shinkei Scishin Yakurigaku Zasshi 2000 Aug; 20(3): 123–30
Bocca ML, Le Doze F, Etard O, et al. Residual effects 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(4): 373–9
Allain H, Bentué-Ferrer D, Tarral A, et al. Effects on postural oscillation and memory functions of a single dose of zolpidem 5 mg, zopiclone 3.75 mg and lormetazepam 1 mg in elderly healthy subjects. A randomized, cross-over, double-blind study versus placebo. Eur J Clin Pharmacol 2003 Jul; 59(3): 179–88
Troy SM, Lucki I, Unruh MA, et al. Comparison of the effects of zaleplon, zolpidem, and triazolam on memory, learning, and psychomotor performance. J Clin Psychopharmacol 2000 Jun; 20(3): 328–37
Cluydts R, De Roeck J, Cosyns P, et al. Antagonizing the effects of experimentally induced sleep disturbance in healthy volunteers by lormetazepam and zolpidem. J Clin Psychopharmacol 1995; 15(2): 132–7
Sicard BA, Trocherie S, Moreau J, et al. Evaluation of zolpidem on alertness and psychomotor abilities among aviation ground personnel and pilots. Aviat Space Environ Med 1993; 64(5): 371–5
Allain H, Patat A, Lieury A, et al. Comparative study of the effects of zopiclone (7.5 mg), zolpidem, flunitrazepam and a placebo on nocturnal cognitive performance in healthy subjects, in relation to pharmacokinetics. Eur Psychiatry 1995; 10 Suppl. 3: 129–35s
Isawa S, Suzuki M, Uchiumi M, et al. The effect of zolpidem and zopiclone on memory. Nihon Shinkei Scishin Yakurigaku Zasshi 2000; 20(2): 61–9
Greenblatt DJ, Harmatz JS, von Moltke LL, et al. Comparative kinetics and dynamics of zaleplon, zolpidem, and placebo. Clin Pharmacol Ther 1998; 64(5): 553–61
Danjou P, Paty I, Fruncillo R, et al. A comparison of the residual effects of zaleplon and zolpidem following administration 5 to 2 h before awakening. Br J Clin Pharmacol 1999; 48(3): 367–74
Hindmarch I, Patat A, Stanley N, et al. Residual effects of zaleplon and zolpidem following middle of the night administration five hours to one hour before awakening. Hum Psychopharmacol 2001 Mar; 16(2): 159–67
Drover D, Lemmens H, Naidu S, et al. Pharmacokinetics, pharmacodynamics, and relative pharmacokinetic/pharmacodynamic profiles of zaleplon and zolpidem. Clin Ther 2000; 22(12): 1443–61
Berlin I, Warot D, Hergueta T, et al. Comparison of the effects of zolpidem and triazolam on memory functions, psychomotor performances, and postural sway in healthy subjects. J Clin Psychopharmacol 1993; 13(2): 100–6
Mintzer MZ, Frey JM, Yingling JE, et al. Triazolam and zolpidem: a comparison of their psychomotor, cognitive, and subjective effects in healthy volunteers. Behav Pharmacol 1997 Nov; 8: 561–74
Rush CR, Griffiths RR. Zolpidem, triazolam, and temazepam: behavioral and subject-rated effects in normal volunteers. J Clin Psychopharmacol 1996; 16(2): 146–57
Garber M, Burke J, Farber R, et al. Residual effects of middle-of-the night dosing: a placebo-controlled, crossover study of indiplon immediate release, zolpidem, and zopiclone in healthy volunteers [abstract no. NR539]. 157th Annual Meeting of the American Psychiatric Association: new research abstracts; 2004 May 4–6; New York: 202: (abstracts on disk)
Bocca ML, Denise P. Residual effects of hypnotics on disengagement of spatial attention. J Psychopharmacol (Oxf) 2000; 14(4): 401–5
Erman MK, Erwin CW, Gengo FM, et al. Comparative efficacy of zolpidem and temazepam in transient insomnia. Hum Psychopharmacol Clin Exp 2001; 16(2): 169–76
Wesensten NJ, Balkin TJ, Belenky GL. Effects of daytime administration of zolpidem versus triazolam on memory. Eur J Clin Pharmacol 1995; 48(2): 115–22
Wesensten NJ, Balkin TJ, Belenky GL. Effects of daytime administration of zolpidem and triazolam on performance. Aviat Space Environ Med 1996; 67(2): 115–20
Hesse LM, von Moltke LL, Greenblatt DJ. Clinically important drug interactions with zopiclone, zolpidem and zaleplon. CNS Drugs 2003; 17(7): 513–32
Drover DR. Comparative pharmacokinetics and pharmacodynamics of short-acting hypnosedatives: zaleplon, zolpidem and zopiclone. Clin Pharmacokinet 2004; 43(4): 227–38
Kudo Y, Shimada O, Maeda Y, et al. Phase I study of zolpidem: single and multiple dose studies [in Japanese]. Rinsho Iyaku 1990; 6(4): 651–75
Greenblatt DJ, Harmatz JS, Von Moltke LL, etal. Comparative kinetics and response to the benzodiazepine agonists triazolam and zolpidem: evaluation of sex-dependent differences. J Pharmacol Exp Ther 2000 May; 293(2): 435–43
Olubodun JO, Ochs HR, von Moltke LL, et al. Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men. Br J Clin Pharmacol 2003 Sep; 56(3): 297–304
Olubodun JO, Ochs HR, Trüten V, et al. Zolpidem pharmacokinetic properties in young females: influence of smoking and oral contraceptive use. J Clin Pharmacol 2002; 42(10): 1142–6
British National Formulary. No. 47. London: British Medical Association and Royal Pharmaceutical Society of Great Britain, 2004 Mar
Scharf MB, Roth T, Vogel GW, et al. A multicenter, placebo-controlled study evaluating zolpidem in the treatment of chronic insomnia. J Clin Psychiatry 1994; 55(5): 192–9
Monti JM, Monti D, Estévez F, et al. Sleep in patients with chronic primary insomnia during long-term zolpidem administration and after its withdrawal. Int Clin Psychopharmacol 1996; 11(4): 255–63
Lahmeyer H, Wilcox CS, Kann J, et al. Subjective efficacy of zolpidem in outpatients with chronic insomnia: a double-blind comparison with placebo. Clin Drug Invest 1997; 13(3): 134–44
Dockhorn RJ, Dockhorn DW. Zolpidem in the treatment of short-term insomnia: a randomized, double-blind, placebo-controlled clinical trial. Clin Neuropharmacol 1996; 19(4): 333–40
Asnis GM, Chakraburtty A, DuBoff EA, et al. Zolpidem for persistent insomnia in SSRI-treated depressed patients. J Clin Psychiatry 1999; 60(10): 668–76
Elie R, Rüther E, Farr I, et al. Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. J Clin Psychiatry 1999; 60(8): 536–44
Fry J, Scharf M, Mangano R, et al. Zaleplon improves sleep without producing rebound effects in outpatients with insomnia. Zaleplon Clinical Study Group. Int Clin Psychopharmacol 2000 May; 15(3): 141–52
Ware CJ, Walsh JK, Scharf MB, et al. Minimal rebound insomnia after treatment with 10-mg zolpidem. Clin Neuro-pharmacol 1997; 20: 116–25
Rosenberg J, Ahlstrøm F. Randomized, double blind trial of zolpidem 10 mg versus triazolam 0.25 mg for treatment of insomnia in general practice. Scand J Prim Health Care 1994; 12(2): 88–92
Silvestri R, Ferrillo F, Murri L, et al. Rebound insomnia after abrupt discontinuation of hypnotic treatment: double-blind randomized comparison of zolpidem versus triazolam. Hum Psychopharmacol 1996; 11: 225–33
Tsutsui S, Katsura T, Kawano T, et al. Clinical study on zolpidem, sleep-inducing agent, in the fields of internal medicine and psychosomatic medicine: double blind comparative study with triazolam as reference drug [in Japanese]. Rinsho Iyaku 1993; 9(2): 387–413
Monti JM, Attali P, Monti D, et al. Zolpidem and rebound insomnia: a double-blind, controlled polysomnographic study in chronic insomniac patients. Pharmacopsychiatry 1994; 27(4): 166–75
Walsh JK, Erman M, Erwin CW, et al. Subjective hypnotic efficacy of trazodone and zolpidem in DSMIII-R primary insomnia. Hum Psychopharmacol 1998; 13: 191–8
Schadeck B, Chelly M, Amsellem D, et al. Efficacité comparative de la doxylamine (15mg) et du zolpidem (10mg) dans le traitement de l’insomnie commune: une étude contrôlée versus placebo. Sem Hop 1996; 72(13-14): 428–39
Tsutsui S. A double-blind comparative study of zolpidem versus zopiclone in the treatment of chronic primary insomnia. Zolpidem Study Group. J Int Med Res 2001 May 30; 29(3): 163–77
Alvarez-Rueda JM, Gutiérrez-Aguilar J, Rosales J, et al. El efecto del zolpidem en los pacientes con insomnio de corta evolución. Salud Mental 2001; 24(1): 33–42
Kudo Y, Kawakita Y, Saito M, et al. Clinical efficacy and safety of zolpidem on insomnia: a double-blind comparative study with zolpidem and nitrazepam [in Japanese]. Rinsho Iyaku 1993; 9(1): 79–105
Kazamatsuri H, Yamashita I, Sato M, et al. Clinical evaluation of zolpidem on insomnia of patients with schizophrenia and manic-depressive psychosis: double-blind trial in comparison with nitrazepam [in Japanese]. Rinsho Iyaku 1993; 9(1): 107–36
Ancoli-Israel S, Walsh JK, Mangano RM, et al. Zaleplon, a novel nonbenzodiazepine hypnotic, effectively treats insomnia in elderly patients without causing rebound effects. Primary Care Companion J Clin Psychiatry 1999 Aug; 1(4): 114–20
Leppik IE, Roth-Schechter GB, Gray GW, et al. Double-blind, placebo-controlled comparison of zolpidem, triazolam, and temazepam in elderly patients with insomnia. Drug Dev Res 1997; 40: 230–8
Roger M, Attali P, Coquelin J-P. Multicenter, double-blind, controlled comparison of zolpidem and triazolam in elderly patients with insomnia. Clin Ther 1993; 15(1): 127–36
Walsh JK, Roth T, Randazzo A, et al. Eight weeks of non-nightly use of zolpidem for primary insomnia. Sleep 2000 Dec 15; 23(8): 1087–96
Perlis ML, McCall WV, Krystal AD, et al. Long-term, non-nightly administration of zolpidem in the treatment of patients with primary insomnia. J Clin Psychiatry 2004 Aug; 65(8): 1128–37
Allain H, Arbus L, Schuck S, et al. Efficacy and safety of zolpidem administered ‘as needed’ in primary insomnia: results of a double-blind, placebo-controlled study. Clin Drug Invest 2001; 21(6): 391–400
Hajak G, Cluydts R, Declerck A, et al. Continuous versus non-nightly use of zolpidem in chronic insomnia: results of a large-scale, double-blind, randomized, outpatient study. Int Clin Psychopharmacol 2002 Jan; 17(1): 9–17
Cluydts R, Peeters K, De Bouyalsky I, et al. Comparison of continuous versus intermittent administration of zolpidem in chronic insomniacs: a double-blind, randomized pilot study. J Int Med Res 1998; 26(1): 13–24
Hajak G, Bandelow B, Zulley J, et al. ‘As needed’ pharmaco-therapy combined with stimulus control treatment in chronic insomnia — assessment of a novel intervention strategy in a primary care setting. Ann Clin Psychiatry 2002 Mar; 14(1): 1–7
Lévy P, Massuel M-A, Gérard DA. ‘As-needed’ prescription of zolpidem for insomnia in routine general practice. Clin Drug Invest 2004; 24(11): 625–32
Pharmacia & Upjohn Company. Halcion® triazolam tablets, USP, prescribing information [online]. Available from URL: http://www.pfizer.com/download/uspi_halcion.pdf [Accessed 2004 Feb 17]
King Pharmaceuticals Inc. Sonata® (zaleplon): prescribing information [online]. Available from URL: http://www.kingpharm.com [Accessed 2004 Aug 19]
Mendelson WB, Roth T, Cassella J, et al. The treatment of chronic insomnia: drug indications, chronic use and abuse liability. Summary of a 2001 new clinical drug evaluation unit meeting symposium. Sleep Med Rev 2004; 8(1): 7–17
Maarek L, Cramer P, Attali P, et al. The safety and efficacy of zolpidem in insomniac patients: a long-term open study in general practice. J Int Med Res 1992; 20(2): 162–70
Schlich D, L’Heritier C, Coquelin JP, et al. Long-term treatment of insomnia with zolpidem: a multicentre general practitioner study of 107 patients. J Int Med Res 1991; 19(3): 271–9
Scharf MB, Mendels J, Thorpy M, et al. Safety of long-term zolpidem treatment in patients with insomnia. Cur Ther Res 1994; 55(9): 1100–11
Hypnotic dependence: zolpidem and zopiclone too. Prescrire Int 2001 Feb; 10(51): 15
Lader M. Withdrawal reactions after stopping hypnotics in patients with insomnia. CNS Drugs 1998 Dec; 10(6): 425–40
Bautista AHP, Buenaventura RD. Zolpidem in insomnia 3-year post-marketing surveillance study in the Philippines. Philippine Journal of Psychiatry 1998; 22(2): 12–7
Ganzoni E, Santoni JP, Chevillard V, et al. Zolpidem in insomnia: a 3-year post-marketing surveillance study in Switzerland. J Int Med Res 1995; 23: 61–73
Ahrens J. Behandlung von Schlafstörungen mit Zolpidem Wirksamkeit ohne abhängigkeitspotential. Therapiewoche Schweiz 1993; 9(10): 660–2
Hajak G, Bandelow B. Safety and tolerance of zolpidem in the treatment of disturbed sleep: a post-marketing surveillance of 16 944 cases. Int Clin Psychopharmacol 1998; 13(4): 157–67
Ganzoni E, Gugger M. Safety profile of zolpidem: two studies in 3805 patients with Swiss practitioners [in German]. Schweiz Rundsch Med Prax 1999; 88(25-26): 1120–7
Canaday BR. Amnesia possibly associated with zolpidem administration. Pharmacotherapy 1996; 16(4): 687–9
Toner LC, Tsambiras BM, Catalano G, et al. Central nervous system side effects associated with zolpidem treatment. Clin Neuropharmacol 2000; 23(1): 54–8
Dündar Y, Boland A, Strobl J, et al. Newer hypnotic drugs for the short-term management of insomnia: a systematic review and economic evaluation. Health Technology Assessment, 2004 Jun; 8 (24)
Pierfitte C, Macouillard G, Thicoîpe M, et al. Benzodiazepines and hip fractures in elderly people: case-control study. Br Med J 2001; 322(7288): 704–8
Wang PS, Bohn RL, Glynn RJ, et al. Zolpidem use and hip fractures in older people. J Am Geriatr Soc 2001 Dec; 49: 1685–90
Oude Voshaar RC, van Balkom AJLM, et al. Zolpidem is not superior to temazepam with respect to rebound insomnia: a controlled study. Eur Neuropsychopharmacol 2004; 14(4): 301–6
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(5): 287–303
Hajak G, Müller WE, Wittchen HU, et al. Abuse and dependence potential for the non-benzodiazepine hypnotics zolpidem and zopiclone: a review of case reports and epidemiological data. Addiction 2003 Oct; 98(10): 1371–8
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: 161–165s
International Narcotics Control Board. List of psychotropic substances under international control [online]. Available from URL: http://www.incb.org/e/list/green.pdf [Accessed 2004 Aug 6]
Walsh JK. Clinical and socioeconomic correlates of insomnia. J Clin Psychiatry 2004; 65 Suppl. 8: 13–9
National Institute for Clinical Excellence. Guidance on the use of zaleplon, zolpidem and zopiclone for the short-term management of insomnia [online]. Available from URL: http://www.nice.org.uk/pdf/TA077fullguidance.pdf [Accessed 2004 May 25]
Morin CM. Measuring outcomes in randomized clinical trials of insomnia treatments. Sleep Med Rev 2003; 7(3): 263–79
McCall WV, D’Agostino R, Dunn A. A meta-analysis of sleep changes associated with placebo in hypnotic clinical trials. Sleep Med 2003; 4(1): 57–62
Verster JC, Veldhuijzen DS, Volkerts ER. Residual effects of sleep medication on driving ability. Sleep Med Rev 2004; 8(4): 309–25
Estivill E, Bové A, Garcïa-Borreguero D, et al. Consensus on drug treatment, definition and diagnosis for insomnia. Clin Drug Invest 2003; 23(6): 351–85
Pliva Pharma Ltd. Zopiclone 7.5mg tablets: summary of product characteristics [online]. Available from URL: http://emc.medicines.org.uk [Accessed 2004 Aug 19]
Allain H, Bentué-Ferrer D, Le Breton S, et al. Preference of insomniac patients between a single dose of zolpidem 10 mg versus zaleplon 10 mg. Hum Psychopharmacol 2003 Jul; 18(5): 369–74
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Various sections of the manuscript reviewed by: S. Ancoli-Israel, Department of Psychiatry, University of California, San Diego, California, USA; D.J. Nutt, Department of Community Based Medicine, University of Bristol, Bristol, UK; M.L. Perlis, Psychiatry M&D Psychology, University of Rochester, Rochester, New York, USA; D.J. Riemann, Department of Psychiatry and Psychotherapy, University Hospital Freiburg, Freiburg, Germany; M.B. Scharf, Department of Psychiatry, Wright State University School of Medicine, Dayton, Ohio, USA; R. Silvestri, Dipartimento di Neuroscienze, Scienze Psichiatriche ed Anestesiologiche, Università Degli Studi Di Messina, Messina, Italy; J.C. Verster, Department of Psychopharmacology, University of Utrecht, Utrecht, The Netherlands.
Data Selection Sources: Medical literature published in any language since 1980 on zolpidem, identified using Medline and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.
Search strategy: Medline search terms were ‘zolpidem’. EMBASE search terms were ‘zolpidem’. AdisBase search terms were ‘zolpidem’. Searches were last updated 2 December 2004.
Selection: Studies in patients with insomnia who received zolpidem. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Zolpidem, insomnia, nonbenzodiazepine, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.
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Harrison, T.S., Keating, G.M. Zolpidem. CNS Drugs 19, 65–89 (2005). https://doi.org/10.2165/00023210-200519010-00008
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DOI: https://doi.org/10.2165/00023210-200519010-00008