Abstract
Sleep disturbances are common and prevalence rates increase with age. Especially in the elderly, somatic diseases and medications with adverse effects relating to sleep are frequent reasons for disturbed and nonrefreshing sleep. It should be emphasised that these reasons must be excluded before symptomatic therapy is started. In some cases the use of hypnosedatives may be included as part of the treatment of a somatic disease and may cause sleep disturbances. Pharmacotherapy is one of the main approaches in the management of primary insomnia and should be part of a broader treatment strategy including nonpharmacological methods.
This article focuses on the tolerability of frequently prescribed hypnosedatives in the elderly with primary insomnia and addresses the primary care physician. In general, recommendations for the pharmacotherapy of insomnia in elderly patients include using a reduced dosage. For some substances (e.g. Zolpidem, zopiclone, zaleplon, temazepam and triazolam) the recommended dosage is half that recommended for younger patients. The properties of the selected hypnosedative should be taken into consideration and matched with the type of sleep disturbance experienced by the patient. Ultrashort-acting drugs may be useful when initiating sleep is the main problem, whereas shortand intermediate-acting substances are recommended for maintaining sleep. Possible interactions with pre-existing medication must also be taken into consideration.
Some agents such as antipsychotics, antidepressants, melatonin and herbal agents may be used in specific indications. However, only a few of these substances have proven tolerability in the elderly and further investigations are recommended.
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References
Quera-Salva MA, Orluc A, Goldenberg F, et al. Insomnia and use of hypnotics: study of a French population. Sleep 1991; 14(5): 386–91
Walsh J. Socio-economic costs of insomnia. Consensus Conference on Insomnia. Versaille: World Health Organization, 1996
Meilinger GD, Balter MB, Uhlenhuth EH. Insomnia and its treatment: prevalence and correlates. Arch Gen Psychiatry 1985; 42(3): 225–32
Hajak G. Epidemiology of severe insomnia and its consequences in Germany. Eur Arch Psychiatry Clin Neurosci 2001; 251(2): 49–56
Chevalier H, Los F, Boichut D, et al. Evaluation of severe insomnia in the general population: results of a European multinational survey. J Psychopharmacol 1999; 13(4): S21–4
Asplund R. Sleep disorders in the elderly. Drugs Aging 1999; 14(2): 91–103
Woodward M. Insomnia in the elderly. Aust Fam Physician 1999; 7: 653–8
Ancoli-Israel S. Insomnia in the elderly: a review for the primary care practitioner. Sleep 2000; 23Suppl. 1: S23–30
Simen S, Rodenback A, Schlaf G, et al. Sleep complaints and hypnotic use by the elderly: results of a representative survey in West Germany [in German]. Wien Med Wochenschr 1996; 146(13–14): 306–9
Seppala M, Hyyppa MT, Impivaara O, et al. Subjective quality of sleep and use of hypnotics in an elderly urban population. Aging (Milano) 1997; 9(5): 327–34
Wilkinson G. The effect of liver disease and aging on the disposition of diazepam, chlordiazepoxide, oxazepam and lorazepam in man. Acta Psychiatr Scand 1978; 274: 56–74
Grad RM. Benzodiazepines for insomnia in community-dwelling elderly: a review of benefit and risk. J Fam Pract 1995; 41(5): 473–81
Vogel GW, Morris D. The effects of estazolam on sleep, performance, and memory: a long-term sleep laboratory study of elderly insomniacs. J Clin Pharmacol 1992; 32(7): 647–51
Hauri P. Sleep hygiene, relaxation therapy and cognitive interventions. In: Hauri P, editor. Case studies in insomnia. New York (NY): Plenum, 1991: 65–84
Hajak G, Rüther E. Insomnie. Heidelberg: Springer, 1995
Clarenbach P, Steinberg R, Weess HG, et al. Empfehlungen zu Diagnostik und Therapie der Insomnie (DGSM). Nervenarzt 1995; 66(10): 723–9
Walsh J, Benca R, Bonnet M, et al. Insomnia: assessment and management in primary care. Bethesda (MD): National Institute of Health, 1998
The World Psychiatric Association. T.W.P.A Task Force on sedative hypnotics. Eur Psychiatr 1993; 8: 45–9
Hajak G, Cluydts R, Estivill E, et al. Efficacy of discontinuous Zolpidem in primary insomnia [abstract]. World J Biol Psychiatr 2001; 2Suppl. 1: P033–01
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
Walsh JK, Roth T, Randazzo A, et al. Eight weeks of nonnightly use of Zolpidem for primary insomnia. Sleep 2000; 23(8): 1087–96
Shorr RI, Robin DW. Rational use of benzodiazepines in the elderly. Drugs Aging 1994; 4(1): 9–20
Hajak G. Insomnia in primary care. Sleep 2000; 23Suppl. 3: S54–63
Hakamies-Blomqvist L, Johansson K, Lundberg C. Medical screening of older drivers as a traffic safety measure — a comparative Finnish-Swedish evaluation study. J Am Geriatr Soc 1996; 44(6): 650–3
Nakra BR, Gfeller JD, Hassan R. A double-blind comparison of the effects of temazepam and triazolam on residual, daytime performance in elderly insomniacs. It Psychogeriatr 1992; 4(1): 45–53
Ray WA, Griffin MR, Downey W. Benzodiazepines of long and short elimination half-life and the risk of hip fracture. JAMA 1989; 262(23): 3303–7
Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis: I. Psychotropic drugs. J Am Geriatr Soc 1999; 47(1): 30–9
Blain H, Blain A, Trechot P, et al. The role of drugs in falls in the elderly: epidemiologic aspects [in french]. Presse Med 2000; 29(12): 673–80
Forsen L, Meyer HE, Sogaard AJ, et al. Mental distress and risk of hip fracture: do broken hearts lead to broken bones? J Epidemiol Community Health 1999; 53(6): 343–7
Moore N, Pierfitte C, Pehourcq F, et al. Comparison of patient questionnaires, medical records and plasma assays in assessing exposure to benzodiazepines in elderly subjects. Clin Pharmacol Ther 2001; 69(6): 445–50
Roger M, Attali P, Coquelin JP. Multicenter, double-blind, controlled comparison of Zolpidem and triazolam in elderly patients with insomnia. Clin Ther 1993; 15(1): 127–36
Vgontzas AN, Kales A, Bixler EO, et al. Temazepam 7.5 mg: effects on sleep in elderly insomniacs. Eur J Clin Pharmacol 1994; 46(3): 209–13
Overstall PW, Oldman PN. A comparative study of lormetazepam and chlormethiazole in elderly in-patients. Age Ageing 1987; 16(1): 45–51
Wheatley D. Prescribing short-acting hypnosedatives. Current recommendations from a safety perspective. Drug Saf 1992; 7(2): 106–15
Camacho ME, Morin CM. The effect of temazepam on respiration in elderly insomniacs with mild sleep apnea. Sleep 1995; 18(8): 644–5
Benkert O, Hippius H. Kompendium der Psychiatrischen Pharmakotherapie. Vol. 2. Berlin: Springer, 2000
Darcourt G, Pringuey D, Salliere D, et al. The safety and tolerability of Zolpidem: an update. J Psychopharmacol 1999; 13(1): 81–93
Hajak G. A comparative assessment of the risks and benefits of zopiclone: a review of 15 years’ clinical experience. Drug Saf 1999; 21(6): 457–69
Holm KJ, Goa KL. Zolpidem: an update of its pharmacology, therapeutic efficacy and tolerability in the treatment of insomnia. Drugs 2000; 59(4): 865–89
Noble S, Langtry HD, Lamb HM. Zopiclone: an update of its pharmacology, clinical efficacy and tolerability in the treatment of insomnia. Drugs 1998; 55(2): 277–302
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: 150–61
Fachinformation Sonata 5mg/-10mg® [prescribing information]. Berkshire: Wyeth Europe Ltd, 2001.
Eckert A, Reiff J, Muller ME. Medical interactions with antidepressives: benefits of the specific serotonin reuptake inhibitor Citalopram [in German]. Med Monatsschr Pharm 1998; 21(5): 138–50
George CF. Perspectives on the management of insomnia in patients with chronic respiratory disorders. Sleep 2000; 23Suppl. 1: S31–5
Hurst M, Noble S. Zaleplon. CNS Drugs 1999; 11(5): 387–92
Hedner J, Yaeche R, Emilien G, et al. Zaleplon shortens subjective sleep latency and improves subjective sleep quality in elderly patients with insomnia. The Zaleplon Clinical Investigator Study Group. Int J Geriatr Psychiatr 2000; 15(8): 704–12
Pichard L, Gillet G, Bonfils C, et al. Oxidative metabolism of Zolpidem by human liver cytochrome P450S. Drug Metab Dispos 1995; 23(11): 1253–62
Copinschi G, Akseki R, Moreno-Reyes R, et al. Effects of bedtime administration of Zolpidem on circadian and sleeprelated hormonal profiles in normal women. Sleep 1995; 18(6): 417–24
Parrino L, Terzano MG. Polysomnographic effects of hypnotic drugs: a review. Psychopharmacology (Berl) 1996; 126(1): 1–16
Scharf MB, Mayleben DW, Kaffeman M, et al. Dose response effects of Zolpidem in normal geriatric subjects. J Clin Psychiatry 1991; 52(2): 77–83
Walsh J, Roehrs T, Declerck A. Polysomnographic studies of the effects of Zolpidem in patients with insomnia. In: Freeman H, Puech A, Roth TE, editors. Zolpidem: an update of its pharmacological properties and therapeutic place in the management of insomnia. Paris: Elsevier, 1996: 129–39
Monti J, Monti D. Pharmacological treatment of chronic insomnia. CNS Drugs 1995; 4: 182–94
Guerault E, Chaumet-Riffaud A, Morselli P. Neurological adverse event profile in the elderly with Zolpidem 5 mg and 10 mg: a retrospective evaluation of European phase II and III studies [abstract]. J Sleep Res 1992; 1Suppl. 1: 89
Chaumet-Riffaud A, Desforges C, Lavoisy J. Review of the post-marketing surveillance experience collected with Zolpidem during the first three years after launch in Europe [abstract]. J Sleep Res 1992; 1Suppl. 1: 40
Unden M, Roth-Schechter B. Next day effects after nighttime treatment with Zolpidem: a review. Eur Psychiatry 1996; 11Suppl. 1: 21S–30S
Shelton PS, Hocking LB. Zolpidem for dementia-related insomnia and nighttime wandering. Ann Pharmacother 1997; 31(3): 319–22
Klimm HD, Dreyfus JF, Delmotte M. Zopiclone versus nitrazepam: a double-blind comparative study of efficacy and tolerance in elderly patients with chronic insomnia. Sleep 1987; 10 Suppl. 1: 73–8
Lofaso F, Goldenberg F, Thebault C, et al. Effect of zopiclone on sleep, night-time ventilation, and daytime vigilance in upper airway resistance syndrome. Eur Respir J 1997; 10(11): 2573–7
Elie R, Frenay M, Le Morvan P, et al. Efficacy and safety of zopiclone and triazolam in the treatment of geriatric insomniacs. Int Clin Psychopharmacol 1990; 5Suppl. 2: 39–46
Dehlin O, Rubin B, Rundgren A. Double-blind comparison of zopiclone and flunitrazepam in elderly insomniacs with special focus on residual effects. Curr Med Res Opin 1995; 13(6): 317–24
Walsh JK, Schweitzer PK. Ten-year trends in the pharmacological treatment of insomnia. Sleep 1999; 22(3): 371–5
Corey-Bloom J, Galasko D. Adjunctive therapy in patients with Alzheimer’s disease: a practical approach. Drugs Aging 1995; 7(2): 79–87
Hajak G, Rodenbeck A, Voderholzer U, et al. Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, Polysomnographie study. J Clin Psychiatry 2001; 62(6): 453–63
Vorderholzer U, Berger M, Hohagen F, et al. Trimipramine for primary insomnia: a double-blind, randomized controlled study [abstract]. World J Biol Psychiatry 2001; 2Suppl. 1: 0012–02
Montgomery SA. Safety of mirtazapine: a review. Int Clin Psychopharmacol 1995; 10Suppl. 4: 37–45
Zisapel N. The use of melatonin for the treatment of insomnia. Biol Signals Recept 1999; 8(1–2): 84–9
Garfinkel D, Laudon M, Nof D, et al. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 1995; 346(8974): 541–4
Haimov I, Lavie P, Laudon M, et al. Melatonin replacement therapy of elderly insomniacs. Sleep 1995; 18(7): 598–603
Iguchi H, Kato K, Ibasayhi H. Age-dependent reduction in serum melatonin concentration in healthy human subjects. J Clin Endocrinol Metab 1982; 55: 27–9
Skene DJ, Vivien-Roels B, Sparks DL, et al. Daily variation in the concentration of melatonin and 5-methoxytryptophol in the human pineal gland: effect of age and Alzheimer’s disease. Brain Res 1990; 528(1): 170–4
Brusco LI, Fainstein I, Marquez M, et al. Effect of melatonin in selected populations of sleep-disturbed patients. Biol Signals Recept 1999; 8(1–2): 126–31
Kendler BS. Melatonin: media hype or therapeutic breakthrough? Nurse Pract 1997; 22(2): 66–7, 71-2, 77
Olde Rikkert MG, Rigaud AS. Melatonin in elderly patients with insomnia: a systematic review. Z Gerontol Geriatr 2001; 34(6): 491–7
Beaubrun G, Gray GE. A review of herbal medicines for psychiatric disorders. Psychiatr Serv 2000; 51(9): 1130–4
Ernst E. Herbal medications for common ailments in the elderly. Drugs Aging 1999; 15(6): 423–8
Nachtmann A, Hajak G. Phytopharmaceutic drugs in treatment of sleep disorders [in German]. Internist (Berl) 1996; 37(7): 743–9
Wagner J, Wagner ML, Hening WA. Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia. Ann Pharmacother 1998; 32(6): 680–91
Gold JL, Laxer DA, Dergal JM, et al. Herbal-drug therapy interactions: a focus on dementia. Curr Opin Clin Nutr Metab Care 2001; 4(1): 29–34
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Wortelboer, U., Cohrs, S., Rodenbeck, A. et al. Tolerability of Hypnosedatives in Older Patients. Drugs Aging 19, 529–539 (2002). https://doi.org/10.2165/00002512-200219070-00006
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DOI: https://doi.org/10.2165/00002512-200219070-00006