Drugs & Aging

, Volume 22, Issue 9, pp 749–765 | Cite as

Postural Instability and Consequent Falls and Hip Fractures Associated with Use of Hypnotics in the Elderly

A Comparative Review
  • Hervé AllainEmail author
  • Danièle Bentué-Ferrer
  • Elisabeth Polard
  • Yvette Akwa
  • Alain Patat
Review Article


The aim of this review is to establish the relationship between treatment with hypnotics and the risk of postural instability and as a consequence, falls and hip fractures, in the elderly.

A review of the literature was performed through a search of the MEDLINE, Ingenta and PASCAL databases from 1975 to 2005. We considered as hypnotics only those drugs approved for treating insomnia, i.e. some benzodiazepines and the more recently launched ‘Z’-compounds, i.e. zopiclone, zolpidem and zaleplon.

Large-scale surveys consistently report increases in the frequency of falls and hip fractures when hypnotics are used in the elderly (2-fold risk). Benzodiazepines are the major class of hypnotics involved in this context; falls and fractures in patients taking Z-compounds are less frequently reported, and in this respect, zolpidem is considered as at risk in only one study. It is important to note, however, that drug adverse effect relationships are difficult to establish with this type of epidemiological data-mining. On the other hand, data obtained in laboratory settings, where confounding factors can be eliminated, prove that benzodiazepines are the most deleterious hypnotics at least in terms of their effects on body sway. Z-compounds are considered safer, probably because of their pharmacokinetic properties as well as their selective pharmacological activities at benzodiazepine-1 (BZ1) receptors. The effects of hypnotics on balance, gait and equilibrium are the consequence of differential negative impacts on vigilance and cognitive functions, and are highly dose- and time-dependent. Z-compounds have short half-lives and have less cognitive and residual effects than older medications.

Some practical rules need to be followed when prescribing hypnotics in order to prevent falls and hip fractures as much as possible in elderly insomniacs, whether institutionalised or not. These are: (i) establish a clear diagnosis of the sleep disorder; (ii) take into account chronic conditions leading to balance and gait difficulties (motor and cognitive status); (iii) search for concomitant prescription of psychotropics and sedatives; (iv) use half the recommended adult dosage; and (v) declare any adverse effect to pharmacovigilance centres. Comparative pharmacovigilance studies focused on the impact of hypnotics on postural stability are very much needed.


GABAA Receptor Zolpidem Triazolam Zopiclone Postural Instability 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors contributed equally to the discussion of the article and to the writing and preparation of the manuscript.

The authors declare they have no conflict of interest with respect to drug companies that market hypnotics. However, Dr A. Patat was employed in the past by Synthelabo and Wyeth Research, and was involved in the development of both zolpidem and zaleplon. Professor H. Allain carried out several studies with hypnotics (zolpidem, zopiclone), all sponsored by drug companies.

This review was supported by the research team of Pharmacology of Rennes I University and by the CMRR of Brittany. No funding body had a role in the preparation of this review or the decision to submit it for publication.


  1. 1.
    MacDonald JB, MacDonald T. Nocturnal femoral fracture and continuing widespread use of barbiturate hypnotics. BMJ 1977; 2: 483–6PubMedCrossRefGoogle Scholar
  2. 2.
    Ray WA, Griffin MR, Schaffner W, et al. Psychotropic drug use and the risk of hip fracture. N Engl J Med 1987; 316: 363–9PubMedCrossRefGoogle Scholar
  3. 3.
    Tinetti ME. Clinical practice: preventing falls in elderly persons. N Engl J Med 2003; 348: 42–9PubMedCrossRefGoogle Scholar
  4. 4.
    Evans JG. Drugs and falls in later life [letter]. Lancet 2003; 361: 448PubMedCrossRefGoogle Scholar
  5. 5.
    Malmivaara A, Heliovaara M, Knekt P, et al. Risk factors for injurious falls leading to hospitalization or death in a cohort of 19,500 adults. Am J Epidemiol 1993; 138: 384–94PubMedGoogle Scholar
  6. 6.
    Coming RG, Nevitt MC, Cummings SR. Epidemiology of hip fractures. Epidemiol Rev 1997; 19: 244–57CrossRefGoogle Scholar
  7. 7.
    Kreisfeld R. The growing problem of elderly falls. Injury Issues Monitor 2000; 20: 5–6Google Scholar
  8. 8.
    Kannus P, Niemi S, Palvanen M, et al. Continuously increasing number and incidence of fall induced, fracture associated, spinal cord injuries in elderly persons. Arch Intern Med 2000; 160: 2145–9PubMedCrossRefGoogle Scholar
  9. 9.
    Lawlor DA, Patel R, Ebrahim S. Association between falls in elderly women and chronic diseases and drug use: cross sectional study. BMJ 2003; 327: 1–6Google Scholar
  10. 10.
    Stenbacka M, Jansson B, Leifman A, et al. Association between use of sedative or hypnotics, alcohol consumption, or other risk factors and a single injurious fall or multiple injurious falls; a longitudinal general population study. Alcohol 2002; 28: 9–16PubMedCrossRefGoogle Scholar
  11. 11.
    Cumming RG. Epidemiology of medication-related falls and fractures in the elderly. Drugs Aging 1998; 12: 43–53PubMedCrossRefGoogle Scholar
  12. 12.
    Greenblatt DJ, Harmatz JS, Shapiro L, et al. Sensitivity to triazolam in the elderly. N Engl J Med 1991; 324: 1691–8PubMedCrossRefGoogle Scholar
  13. 13.
    Cumming RG, Le Couteur DG. Benzodiazepines and risk of hip fractures in older people: a review of the evidence. CNS Drugs 2003; 17: 825–37PubMedCrossRefGoogle Scholar
  14. 14.
    Leipzig R, Cumming R, Tinetti M. Drugs and falls in older people: a systematic review and meta-analysis: I. Psychotropic drugs. J Am Geriatr Soc 1999; 47: 30–9PubMedGoogle Scholar
  15. 15.
    Lord SR, Anstey KJ, Williams P, et al. Psychoactive medication use, sensorimotor function and falls in older women. Br J Clin Pharmacol 1995; 39: 227–34PubMedCrossRefGoogle Scholar
  16. 16.
    Sanger DJ. The pharmacology and mechanisms of action of new generation, non-benzodiazepine hypnotic agents. CNS Drugs 2004; 1: 9–15CrossRefGoogle Scholar
  17. 17.
    Drover DR. Comparative pharmacokinetics and pharmacodynamics of short-acting hypnosedatives: zaleplon, zolpidem and zopiclone. Clin Pharmacokinet 2004; 43: 227–38PubMedCrossRefGoogle Scholar
  18. 18.
    Thomson Healthcare. Micromedex healthcare [online]. Available from URL: [Accessed 2005 Aug 2]
  19. 19.
    Nowell PD, Mazumdar S, Buysse DJ, et al. Benzodiazepines and zolpidem for chronic insomnia: a meta-analysis of treatment efficacy. JAMA 1997; 278: 2170–7PubMedCrossRefGoogle Scholar
  20. 20.
    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; 56: 297–304PubMedCrossRefGoogle Scholar
  21. 21.
    Panneman MJ, Goettsch WG, Kramarz P, et al. The costs of benzodiazepine-associated hospital-treated fall injuries in the EU: a Pharmo study. Drugs Aging 2003; 20: 833–9PubMedCrossRefGoogle Scholar
  22. 22.
    Le Dictionnaire Vidal. 81st ed. Paris: Vidal, 2005Google Scholar
  23. 23.
    Ensrud KE, Blackwell TL, Mangione CM, et al., for the Study of Osteoporotic Fractures Research Group. Central nervous system-active medications and risk for falls in older women. J Am Geriatr Soc 2002; 50: 1629–37PubMedCrossRefGoogle Scholar
  24. 24.
    Chaimowicz F, Ferreira TJXM, Miguel DFA. Use of psychoactive drugs and related falls among older people living in a community in Brazil. Rev Saude Publica 2002; 34: 631–5CrossRefGoogle Scholar
  25. 25.
    Frels C, Williams P, Narayanan S, et al. Iatrogenic causes of falls in hospitalised elderly patients: a case-control study. Postgrad Med 2002; 78: 487–9CrossRefGoogle Scholar
  26. 26.
    Pierfitte C, Macouillard G, Thicoipe M, et al. Benzodiazepines and hip fractures in elderly people: case control study. BMJ 2001; 322: 704–8PubMedCrossRefGoogle Scholar
  27. 27.
    Ray WA, Griffin MR, Downey W. Benzodiazepines of long and short elimination half-life and risk of hip fracture. JAMA 1989; 262: 3303–7PubMedCrossRefGoogle Scholar
  28. 28.
    Allain H, Delahaye C, Le Coz F, et al. Post-marketing surveillance of zopiclone in insomnia. Sleep 1991; 14: 408–13PubMedGoogle Scholar
  29. 29.
    Wang PS, Bohn RL, Glynn RJ, et al. Zolpidem use and hip fractures in older people. J Am Geriatr Soc 2001; 49: 1685–90PubMedCrossRefGoogle Scholar
  30. 30.
    Bailey L, Ward M, Musa MN. Clinical pharmacokinetics of benzodiazepines. J Clin Pharmacol 1994; 34: 804–11PubMedGoogle Scholar
  31. 31.
    Greenblatt DJ, Divoll M, Abernethy DR, et al. Clinical pharmacokinetics of the newer benzodiazepines. Clin Pharmacokinet 1983; 8: 233–52PubMedCrossRefGoogle Scholar
  32. 32.
    Holbrook AM, Crowter R, Lotter A, et al. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ 2000; 162: 225–33PubMedGoogle Scholar
  33. 33.
    Kyriakopolous AA, Greenblatt DJ, Shader RI. Clinical pharmacokinetics of lorazepam: a review. J Clin Psychiatry 1978; 39: 16–23Google Scholar
  34. 34.
    Luscombe DK. Lormetazepam-plasma concentrations in volunteers following sublingual and oral dosing. Psychopharmacology 1984; 1: 99–104PubMedGoogle Scholar
  35. 35.
    Seyberth HW. Pharmacokinetics and biotransformation of the new benzodiazepine, lormetazepam, in man: III. Repeated administration and transfer to neonates via breast milk. Eur J Clin Pharmacol 1983; 24: 139–40PubMedCrossRefGoogle Scholar
  36. 36.
    Humpel M, Illi V, Milius W, et al. The pharmacokinetics and biotransformation of the new benzodiazepine lormetazepam in humans: I. Absorption, distribution, elimination and metabolism of lormetazepam-5-14C. Eur J Drug Metab Pharmacokinet 1979; 4: 237–43PubMedCrossRefGoogle Scholar
  37. 37.
    Humpel M, Nieuweboer B, Milius W, et al. Kinetics and bio-transformation of lormetazepam: II. Radioimmunologic determinations in plasma and urine of young and elderly subjects: first-pass effect. Clin Pharmacol Ther 1980; 28: 673–9PubMedCrossRefGoogle Scholar
  38. 38.
    Hildebrand M, Hellstern A, Humpel M, et al. Plasma levels and urinary excretion of lormetazepam in patients with liver cirrhosis and in healthy volunteers. Eur J Drug Metab Pharmacokinet 1990; 15: 19–26PubMedCrossRefGoogle Scholar
  39. 39.
    Pakes GE, Brogden RN, Heel RC, et al. Triazolam: a review of its pharmacological properties and therapeutic efficacy in patients with insomnia. Drugs 1981; 22: 81–110PubMedCrossRefGoogle Scholar
  40. 40.
    Kroboth PD, Juhl RP. New drug evaluations: triazolam. Drug Intell Clin Pharm 1983; 17: 495–500PubMedGoogle Scholar
  41. 41.
    Holm KJ, Goa KL. Zolpidem: an update of its pharmacology, therapeutic efficacy and tolerability in the treatment of insomnia. Drugs 2000; 59: 865–89PubMedCrossRefGoogle Scholar
  42. 42.
    Swainston Harrison T, Keating GM. Zolpidem: a review of its use in the management of insomnia. CNS Drugs 2005; 19: 65–89PubMedCrossRefGoogle Scholar
  43. 43.
    Lee YJ. Overview of the therapeutic management of insomnia with zolpidem. CNS Drugs 2004; 1: 17–23CrossRefGoogle Scholar
  44. 44.
    Noble S, Langtry HD, Lamb HM. Zopiclone: an update of its pharmacology, clinical efficacy and tolerability in the treatment of insomnia. Drugs 1998; 55: 277–302PubMedCrossRefGoogle Scholar
  45. 45.
    Montplaisir J, Hawa R, Moller H, et al. Zopiclone and zaleplon vs benzodiazepines in the treatment of insomnia: Canadian consensus statement. Hum Psychopharmacol 2003; 18: 29–38PubMedCrossRefGoogle Scholar
  46. 46.
    Dooley M, Plosker GL. Zaleplon: a review of its use in the treatment of insomnia. Drugs 2000; 60: 413–45PubMedCrossRefGoogle Scholar
  47. 47.
    Barbera J, Shapiro C. Benefit-risk assessment of zaleplon in the treatment of insomnia. Drug Saf 2005; 28: 301–18PubMedCrossRefGoogle Scholar
  48. 48.
    Heydorn WE. Zaleplon: a review of a novel sedative hypnotic used in the treatment of insomnia. Expert Opin Investig Drugs 2000; 9: 841–58PubMedCrossRefGoogle Scholar
  49. 49.
    Herings RM, Stricker BH, De Boer A, et al. Benzodiazepines and the risk of falling leading to femur fractures: dosage more important than elimination half-life. Arch Intern Med 1995; 155: 1801–7PubMedCrossRefGoogle Scholar
  50. 50.
    Slemenda C. Prevention of hip fractures: risk factor modification. Am J Med 1997; 103: 65–73CrossRefGoogle Scholar
  51. 51.
    Kripke DF. Chronic hypnotic use: deadly risks, doubtful benefit. Sleep Med Rev 2000; 4: 5–20PubMedCrossRefGoogle Scholar
  52. 52.
    Darcourt G, Pringuey D, Salliere D, et al. The safety and tolerability of zolpidem: an update. J Psychopharmacol 1999; 13: 81–93PubMedCrossRefGoogle Scholar
  53. 53.
    Hajak G, Bandelow B. Safety tolerance of zolpidem in the treatment of disturbed sleep: a post-marketing surveillance of 16,944 cases. Int Clin Psychopharmacol 1998; 13: 157–67PubMedCrossRefGoogle Scholar
  54. 54.
    Allain H, Monti J. General safety of zolpidem: safety in elderly, overdose and rebound effects. Eur Psychiatry 1997; 12Suppl. 1: 21s–9sCrossRefGoogle Scholar
  55. 55.
    Eto F, Saotome I, Furuichi T, et al. Effects of long-term use of benzodiazepines on gait and standing balance in the elderly. Ann N Y Acad Sci 1998; 860: 543–5PubMedCrossRefGoogle Scholar
  56. 56.
    Cutson TM, Gray SL, Hughes MA, et al. Effect of a single dose of diazepam on balance measures in older people. J Am Geriatr Soc 1997; 45: 435–40PubMedGoogle Scholar
  57. 57.
    Robin DW, Hasan SS, Edeki T, et al. Increased baseline sway contributes to increased losses of balance in older people following triazolam. J Am Geriatr Soc 1996; 44: 300–4PubMedGoogle Scholar
  58. 58.
    Patat A. Clinical pharmacology of psychotropic drugs. Hum Psychopharmacol Clin Exp 2000; 15: 361–87CrossRefGoogle Scholar
  59. 59.
    Bourin M, Briley M. Sedation, an unpleasant, undesirable and potentially dangerous side effect of many psychotropic drugs. Hum Psychopharmacol Clin Exp 2004; 19: 135–9CrossRefGoogle Scholar
  60. 60.
    Swift CG. Postural instability as a measure of sedative drug response. Br J Clin Pharmacol 1984; 18: 87–90CrossRefGoogle Scholar
  61. 61.
    McClelland GR. Body sway and the effects of psychoactive drugs: a review. Hum Psychopharmacol Clin Exp 1989; 4: 3–14CrossRefGoogle Scholar
  62. 62.
    Patat A, Foulhoux P. Effects on postural sway of various benzodiazepine tranquillizers. Br J Clin Pharmacol 1985; 2: 9–16CrossRefGoogle Scholar
  63. 63.
    Patat A, Foulhoux P, Klein MJ. Etude des effets résiduels sur l’equilibre de trois hypnotiques (loprazolam, flunitrazépam, triazolam) appréciés par l’analyse spectrale des oscillations posturales [in French]. Thérapie 1986; 41: 443–7PubMedGoogle Scholar
  64. 64.
    Patat A, Klein MJ, Jones RW. Acute effects on psychomotor performance of binedaline alone and with alcohol. Methods Find Exp Clin Pharmacol 1988; 10: 393–9PubMedGoogle Scholar
  65. 65.
    Patat A, Perault MC, Vandel B, et al. Assessment of the interaction between a partial antagonist and a full agonist of benzodiazepine receptors, based on psychomotor performance and memory in healthy volunteers. J Psychopharmacol 1995; 2: 91–101CrossRefGoogle Scholar
  66. 66.
    Allain H, Patat A, Le Coz F, 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 J Psychiatry 1995; 10: 129s–35sCrossRefGoogle Scholar
  67. 67.
    Patat A, Le Go A, Foulhoux P. Dose-response relationship of vindeburnol based on spectral analysis of posturographic recordings. Eur J Clin Pharmacol 1985; 29: 455–9PubMedCrossRefGoogle Scholar
  68. 68.
    Allain H, Bentué-Ferrer D, Tarral A, et al. Effects on postural oscillation and memory functions of a single dose of zolpidem 5mg, zopiclone 3.75mg and lormetazepam 1mg in elderly healthy subjects: a randomized, cross-over, double-blind study versus placebo. Eur J Clin Pharmacol 2003; 59: 179–88PubMedCrossRefGoogle Scholar
  69. 69.
    Bizzo G, Guillet N, Patat A, et al. Specifications for building a vertical force platform designed for clinical stabilometry. Med Biol Eng Comput 1985; 23: 474–6PubMedCrossRefGoogle Scholar
  70. 70.
    Kapteyn TS, Bles W, Njiokiktjien CJ, et al. Standardization in platform stabilometry being a part of posturography. Agressologie 1983; 24: 321–6PubMedGoogle Scholar
  71. 71.
    Tada K, Sato Y, Sakai T, et al. Effects of zopiclone, triazolam and nitrazepam on standing steadiness. Neuropsychobiology 1994; 29: 17–22PubMedCrossRefGoogle Scholar
  72. 72.
    Robin DW, Hasan SS, Lichtenstein MJ, et al. Dose-related effect of triazolam on postural sway. Clin Pharmacol Ther 1991; 49: 581–8PubMedCrossRefGoogle Scholar
  73. 73.
    Ancoli-Israel S. Insomnia in the elderly: a review for the primary care practitioner. Sleep 2000; 23Suppl. 1: 23–30Google Scholar
  74. 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 Clin Exp 2001; 16: 159–67CrossRefGoogle Scholar
  75. 75.
    Vermeeren A, Danjou PH, O’Hanlon JR. Residual effects of evening and middle of the night administration of zaleplon 10 and 20mg on memory and actual driving. Hum Psychopharmacol Clin Exp 1998; 13: S98–S107CrossRefGoogle Scholar
  76. 76.
    Roehrs T, Rosenthal L, Koshorek BA, et al. Effects of zaleplon or triazolam with or without ethanol on human performance. Sleep Med 2001; 2: 323–32PubMedCrossRefGoogle Scholar
  77. 77.
    Parks V, Leister C, Patat A, et al. Effects of ethanol at a blood alcohol concentration of 0.4 g/L on actual driving and memory. Eur Neuropsychopharmacol 2002; 12Suppl. 3: S432–3CrossRefGoogle Scholar
  78. 78.
    Ray WA, Thapa PW, Gideon P. Benzodiazepines and the risks of falls in nursing home residents. Am J Geriatr Soc 2000; 48: 682–5Google Scholar
  79. 79.
    Ray WA. Psychotropic drugs and injuries among the elderly: a review. J Clin Psychopharmacol 1992; 12: 386–96PubMedGoogle Scholar
  80. 80.
    Avidan AY, Fries BE, James ML, et al. Insomnia and hypnotic use, recorded in the minimum data set, as predictors of falls and hip fractures in Michigan nursing homes. J Am Geriatr Soc 2005; 53: 955–62PubMedCrossRefGoogle Scholar
  81. 81.
    Stevens M, D’Arcy J, Holman C, et al. Preventing falls in older people: impact of an intervention to reduce environmental hazards in the home. J Am Geriatr Soc 2001; 49: 1442–7PubMedCrossRefGoogle Scholar
  82. 82.
    Terzano MG, Rossi M, Palomba V, et al. New drugs for insomnia: comparative tolerability of zopiclone, zolpidem and zaleplon. Drug Saf 2003; 26: 261–82PubMedCrossRefGoogle Scholar
  83. 83.
    Damgen K, Luddens H. Zaleplon displays a selectivity to re-combinant GABAA receptors different from zolpidem, zopiclone and benzodiazepines. Neurosci Res Commun 1999; 25: 139–45CrossRefGoogle Scholar
  84. 84.
    Crestani F, Martin JR, Molher H, et al. Mechanism of action of the hypnotic zolpidem in vivo. Br J Pharmacol 2000; 131: 1251–4PubMedCrossRefGoogle Scholar
  85. 85.
    Sanna E, Busonero F, Talani G, et al. Comparison of the effects of zaleplon, zolpidem, and triazolam at various GABA A receptor subtypes. Eur J Pharmacol 2002; 451: 103–10PubMedCrossRefGoogle Scholar
  86. 86.
    Verster JC, Veldhuijzen DS, Patat A, et al. Hypnotics and driving safety: not half-life but dosage determines the magnitude of driving impairment: meta-analyses of randomized controlled clinical trials applying on-the-road driving test. N Engl J Med. In pressGoogle Scholar
  87. 87.
    Camus M, Pailhous J, Bonnard M. Cognitive tuning of corticospinal excitability during human gait: adaptation to the phase. Eur J Neurosci 2004; 20: 1101–7PubMedCrossRefGoogle Scholar
  88. 88.
    Mattila MJ, Vanakovski J, Kalska H, et al. Effects of alcohol, zolpidem, and some other sedatives and hypnotics on human performance and memory. Pharmacol Biochem Behav 1998; 59: 917–23PubMedCrossRefGoogle Scholar
  89. 89.
    Vermeeren A. Residual effects of hypnotics epidemiology and clinical implications. CNS Drugs 2004; 18: 297–328PubMedCrossRefGoogle Scholar
  90. 90.
    Heckman GA, Papaioannou A, Gagnon M, et al. The effect of cholinesterase inhibitors on the risk of falls and injuries in patients with mild to moderate Alzheimer’s dementia (protocol for a Cochrane review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 4. Oxford: Update Software, 2002Google Scholar
  91. 91.
    Maeker E, Bombois S, Pardessus V, et al. Troubles cognitifs et chutes: l’expérience de la consultation multidisciplinaire de la chute de Lille [in French]. Rev Neurol (Paris) 2005; 161: 419–26CrossRefGoogle Scholar
  92. 92.
    Hajak G, Cluydts R, Allain H, et al. The challenge of chronic insomnia: is non nightly hypnotic treatment a feasible alternative. Eur Psychiatry 2003; 18: 201–8PubMedCrossRefGoogle Scholar
  93. 93.
    Estivill E, Bove A, Garcia-Borreguero D, et al. Consensus on drug treatment, definition and diagnosis for insomnia. Clin Drug Invest 2003; 23: 351–85CrossRefGoogle Scholar
  94. 94.
    Avidan AY. Sleep changes and disorders in the elderly patient. Curr Neurol Neurosci Rep 2002; 2: 178–85PubMedCrossRefGoogle Scholar
  95. 95.
    Mayor S. NICE issues guidelines to prevent falls in elderly people. BMJ 2004; 329: 1258Google Scholar
  96. 96.
    Marks R, Allegrante JP, Mackenzie CR, et al. Hip fractures among the elderly: causes, consequences and control. Ageing Res Rev 2003; 2: 57–93PubMedCrossRefGoogle Scholar
  97. 97.
    Dundar Y, Dodd S, Strobl J, et al. Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and metaanalysis. Hum Psychopharmacol Clin Exp 2004; 19: 305–32CrossRefGoogle Scholar
  98. 98.
    Elwyn G, Gwyn R. Stories we hear and stories we tell: analysing talk in clinical practice. BMJ 2005; 318: 186–8CrossRefGoogle Scholar
  99. 99.
    Allain H, Bentué-Ferrer D, Le Breton S, et al. Preference of insomniac patients between a single dose of zolpidem 10mg versus zaleplon 10mg. Hum Psychopharmacol Clin Exp 2003; 18: 369–74CrossRefGoogle Scholar
  100. 100.
    Sullivan SK, Petroski RE, Verge G, et al. Characterization of the interaction of indiplon, a novel pyrazolopyrimidine sedativehypnotic, with the GABAA receptor. J Pharmacol Exp Ther 2004; 311: 537–46PubMedCrossRefGoogle Scholar
  101. 101.
    Kato K, Hirri K, Nischiyama K, et al. Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist. Neuropharmacology 2005; 48: 301–10PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Hervé Allain
    • 1
    Email author
  • Danièle Bentué-Ferrer
    • 1
  • Elisabeth Polard
    • 2
  • Yvette Akwa
    • 3
  • Alain Patat
    • 4
  1. 1.Laboratory of Experimental and Clinical Pharmacology, Pôle des Neurosciences and Centre Memory Resources Research (CMRR), Faculty of MedicineUniversity of Rennes IRennes CedexFrance
  2. 2.Rennes Medical School, Centre Régional de PharmacovigilanceHôpital PontchaillouRennes CedexFrance
  3. 3.Inserm Unité 488Le Kremlin Bicêtre CedexFrance
  4. 4.Biotrial SATechnopôle Rennes-AtalanteRennesFrance

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