Assessment and treatment of sleep disturbances in aged population 167
conclusive evidence that any of these preparations has any significant hypnotic effect in non-toxic doses.
168 T.R. Shah, N.N. Trajanovic and C.M. Shapiro
Assessment and treatment
The diagnosis of RLS can be made from the patient’s history, whereas for PLMD a PSG sleep study, actigraphy or immobilization test can be used [75]. In the case of an impaired elderly person, a detailed history from and of family members and caregivers is considered very useful in diagnosing RLS [74].
Non-pharmacological treatment includes control of stimulants or “aggravating”
drugs (e.g. , caffeine, tobacco, alcohol, antihistamines, certain antidepressants), im-proving sleep hygiene, and regular exercise [61, 75]. It has also been reported that soaking the legs and feet in a warm bath provides relief of RLS in some patients [70]. The mainstay of pharmacological treatment for RLS relies on dopaminergic agonists as the first choice followed by opioids, anticonvulsants and BZDs [77]. The first dopaminergic agent used in treating the nocturnal symptoms of RLS, leading to improved quality of sleep in patients, is l-Dopa and carbidopa, but its use is limited because of its augmentation and rebound side effects with long-term use [61, 77].
Ergot dopamine agonists such as bromocriptine (7.5 mg/night), pergolide (0.5 mg q hs) and cabergoline (2.2 mg/day) are also found to be effective but their use is limited because they are associated with side effects like nausea, fibrosis and car-diac valvulopathy, and toxicity risk is also high with long-term use [61, 77]. A study (PEARLS study [71]) has shown substantial improvement in PLMD and sleep distur-bances associated with RLS in patients taking pergolide. Long-term use of low-dose pergolide maintained its efficacy, and was also well tolerated in this study [71]. Non-ergot dopamine agonists such as pramipexole (0.375–1.5 mg/night) and ropinirole (0.5–1.5 mg/night) are more effective and better tolerated than ergot derivatives [61].
However, the use of dopamine agonists have been limited in elderly population due to possible interaction with multiple other medications and due to various side effects like insomnia [61], orthostatic hypotension, nausea, dizziness [74].
Sedation and sudden sleep attacks were described in a small number of patients, but it is not clear whether the DA medication is an instigating or contributing factor.
The rebound phenomenon related to use of single evening dose of dopamine ago-nists is managed by adding a dose to sustain dopamine release, or using a single dose sustained release formula. The RLS augmentation is seen typically at higher doses of levodopa treatment, and involves extension of symptoms in intensity, vari-ety or diurnal distribution. Switching from levodopa to a dopamine agonist usually ameliorates symptoms. Levopoda and dopamine agonists are also associated with higher incidence of nightmares and visual hallucinations, more often in elderly and in particular in neurodegenerative diseases such as Parkinson’s disease. It is pro-posed that the aberrant dopaminergic regulation of the REM sleep plays role in this phenomenon.
Opioids are well tolerated and seem to have a long-term efficacy in the treatment of RLS for the elderly population [74, 78]. Opioids such as propoxyphene (65–
130 mg) are useful for mild cases of RLS and PLMD, whereas oxycodone (4–
5 mg) and methadone (5–10 mg) are reserved for severe resistant symptoms of RLS and PLMD [61]. A retrospective study by Grewal et al. [79] showed a significant decrease in the number of PLM per hour of total sleep time as shown by pre- and post-treatment overnight PSG studies in patients treated with selegiline (5, 10 and
Assessment and treatment of sleep disturbances in aged population 169
15 mg). The opioids must be used with caution in patients suffering from sleep apnea because of their ability to cause respiratory depression in patients on long-term opioid therapy [61, 74, 78]. BZD such as clonazepam (0.5–2 mg) (occasionally much higher doses are needed), temazepam (7.5–30 mg) can be used as supportive measures in the treatment of RLS-related insomnia, but should be used cautiously in elderly due to side effects such as confusion, ataxia and sedation [19, 61, 74]. A study by Happe et al. [72] has shown that gabapentin in divided doses of 300–1200 mg/day was effective and well tolerated in the treatment of RLS. Other agents that can be beneficial in elderly population suffering from RLS include supplements of folic acid, and intravenous or oral iron [75]. In conclusion, the elderly cherish their sleep as much as any one else. To provide less than the maximum in effort to resolve their sleep problems is ageism at its very worst. The challenges are considerable, but the rewards in this area are worth the effort.
References
1. Feinsilver S (2003) Sleep in the elderly what is normal? Clin Geriatr Med 19: 177–188 2. Fleming J, Shapiro CM, Flanigan M, Hanly P, Kryger M, Levitt A, Abbey S, Broughton
R, Czeisler C (1995) Kommunicom publications, volume 1: Sleep function and insomnia assessment: 2–32 and volume 2 insomnia management: 34–49
3. Shapiro CM (1974) A third state of existence. Leech 44: 13–16
4. Martin J, Shochat T, Ancoli-Israel S (2000) Assessment and treatment of sleep distur-bances in older adults. Clin Psychol Rev 20: 783–805
5. Schneider D (2002) Safe and effective therapy for sleep problems in the older patient.
Geriatrics 57: 24–35
6. Shaver J, Giblin E, Lentz M, Lee K (1988) Sleep patterns and stability in perimenopausal women. Sleep11: 556–561
7. Ledesert B, Ringa V, Breart G (1995) Menopause and perceived health status among the women of the French GAZEL cohort. Maturitas 20: 113–120
8. Moe KE (2004) Hot flashes and sleep in women. Sleep Med Rev 8: 487–497
9. Polo-Kantola P, Erkkola R (2004) Sleep and the menopause. J Br Menopause Soc 10:
145–150
10. Barrett-Connor E, Grady D, Stefanick ML (2005) The rise and fall of menopausal hormone therapy. Annu Rev Public Health 26: 115–140
11. Cohen O, Vinker S, Yaphe J, Kitai E (2005) Hormone replacement therapy and WONCA/COOP functional status: a cross-sectional population-based study of women in Israel. Climacteric 8: 171–176
12. Gambacciani M, Ciaponi M, Cappagli B, Monteleone P, Benussi C, Bevilacqua G, Vacca F, Genazzani AR (2005) Effects of low-dose, continuous combined hormone replacement therapy on sleep in symptomatic postmenopausal women. Maturitas 50: 91–97 13. Ohayon M, Carskadon M, Guilleminault C, Vitiello M (2004) Meta-Analysis of
quan-titative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan. Sleep 27: 1255–1273
14. Swift CG, Shapiro CM (1993) ABC of sleep disorders. Sleep and sleep problems in elderly people. Brit Med J 306: 1468–1471
15. Shin K, Shapiro CM (2003) Menopause, sex hormones, and sleep. Bipolar Disord 5:
106–109, review
16. Tamaki M, Shirota AI, Tanaka H, Hayashi M, Hori T (1999) Effects of a daytime nap in the aged. Psychiatry Clin Neurosci 53: 273–275
170 T.R. Shah, N.N. Trajanovic and C.M. Shapiro
17. Shapiro G, Shen J, Shapiro CM (2004) Sleep changes in the depressed older adults:
Implications for management. Geriatrics and Aging 7: 25–31
18. Sloan E, Flint A, Reinish L, Shapiro CM (1996) Circadian rhythms and psychiatric dis-orders in the elderly. J Geriatr Psychiatry Neurol 9: 164–170
19. Ancoli-Israel S, Steven Poceta J, Stepnowsky C, Martin J, Gehrman P (1997) Identification and treatment of sleep problems in the elderly. Sleep Med Rev 1: 3–17
20. Ancoli-Israel S (1997) Sleep problems in older adults: Putting myths to bed. Geriatrics 52: 20–30
21. Chilcott LA, Shapiro CM (1996) The socioeconomic impact of insomnia: An overview.
PharmacoEconomics 10, Suppl. 1: 1–14
22. Vitiello M (1999) Effective treatments for age-related sleep disturbances. Geriatrics 54:
47–52
23. Kayumov L, Brown G, Jindal R, Buttoo K, Shapiro CM (2001) A randomized, double blind, placebo-controlled crossover study of the effect of exogenous melatonin on delayed sleep phase syndrome. Psychosom Med 63: 40–48
24. Martins Jr E, Oliveira AP, Araujo AM, Lima W, Cipollaneto J, Costa Rosa L (2001) Melatonin modulate allergic lung inflammation. J Pineal Res 31: 363–369
25. Sutherland ER, Ellison MC, Kraft M, Martin RJ (2003) Elevated serum melatonin is associated with the nocturnal worsening of asthma. J Allergy Clin Immunology 112: 513–
517
26. Weekly LB (1993) Effects of melatonin on pulmonary and coronary vessels are exerted through perivascular nerves. Clin Auton Res 3: 45–47
27. Flamer H (1996) Sleep disorders in the elderly. Aust NZ J Medicine 26: 96–104 28. Young T, Palten M, Denpsey J, Shatrud J, Weber S, Badr S (1993) The occurrence of sleep
disordered breathing among middle aged adults. New Engl J Med 328: 1230–1235 29. Schr¨oder CM, O’Hara R (2005) Depression and obstructive sleep apnea (OSA). Annals
of Gen Psychiatry 4: 13
30. Ancoli-Israel S, Klauber MR, Stepnowsky C, Estline E, Chinn A, Fell R (1995) Sleep-disordered breathing in African-American elderly. Am J Respri Crit Care Med 152: 1946–
1949
31. Barthlen G (2002) Sleep disorders – Obstructive sleep apnea syndrome, restless legs syndrome, and insomnia in geriatric patients. Geriatrics 57: 34–39
32. Aloia M, Arnedt J, Davis J, Riggs R, Byrd D (2004) Neuropsychological sequeale of obstructive sleep apnea-hypopnea syndrome: A critical review. J Int Neuropsychol Soc 10: 772–785
33. Carley DW, Radulovacki M (1999) Mirtazapine, a mixed-profile serotonin ago-nist/antagonist, suppresses sleep apnea in the rat. Am J Respir Crit Care Med 160: 1824–
1829
34. Castillo JL, Menendez P, Segovia C, Guilleminault C (2004) Effectiveness of mirtazapine in the treatment of sleep apnea/hypopnea syndrome (SAHS). Sleep Med 5: 507–508 35. Smith PL, Haponik EF, Bleecker ER (1984) The effects of oxygen in patients with sleep
apnea. Am Rev Respir Dis 130: 958–963
36. Gold AR, Bleecker ER, Smith PL (1985) A shift from central and mixed sleep apnea to obstructive sleep apnea resulting from low-flow oxygen. Am Rev Respir Dis 132: 220–223 37. Fletcher EC, Munafo DA (1990) Role of nocturnal oxygen therapy in obstructive sleep
apnoea. Chest 98: 1497–1505
38. DeBacker WA, Verbraecken J, Willemen M, Wittesaele W, DeCock W, Van deHeyning V (1995) Central apnea index decreases after prolonged treatment with acetazolamide. Am J Respir Crit Care Med 151: 87–91
39. Javaheri S (2005) Central sleep apnea in congestive heart failure: prevalence, mechanisms, impact, and therapeutic options. Semin Respir Crit Care Med 26: 44–55
Assessment and treatment of sleep disturbances in aged population 171
40. Benca R (2005) Diagnosis and treatment of chronic insomnia: A review. Psychiatr Serv 56: 332–343
41. Foley DJ, Monjan AA, Brown SL, Simonsick EM, Wallace RB, Blazer DG (1995) Sleep complaints among elderly persons: An epidemiologic study of the three communitries.
Sleep 18: 425–432
42. Shapiro CM, Morris A (2004) Insomnia in older adults, Part I: Assessment geriatrics and aging 7 (7) and 7 (9): 3–8
43. McCall W (2004) Sleep in the elderly: Burden, diagnosis, and treatment. Prim Care Companion J Clin Psychiatry 6: 9–20
44. Shapiro CM, Steingart A (1993) Fifty-one questions for the elderly insomniacs and why.
Sleep disorders and insomnia in the elderly. Facts and Research in Gerontology 7: 223–
232
45. Bachman D (1992) Sleep disorders with aging: Evaluation and treatment. Geriatrics 47:
53–61
46. Morris A, Moller H, Shapiro CM (2004) Insomnia in older adults, Part II: Treatment.
Geriatrics and aging 7: 9–14
47. Sloan E, Hauri P, Bootzin R, Morin C, Stevenson M, Shapiro CM (1993) The nuts and bolts of behavioral therapy for insomnia. J Psychosom Res 37: 19–37
48. Greenblatt DJ, Shader RI, Harmatz JS (1989) Implications of altered drug disposition in the elderly: studies of benzodiazepines. J Clin Pharmacol 29: 866–872
49. Cumming RG, Le Couteur DG (2003) Benzodiazepines and risk of hip fractures in older people: a review of the evidence. CNS Drugs 17: 825–837
50. Vermeeren J (2004) Residual effects of hypnotics: epidemiology and clinical implications.
CNS Drugs 18: 297–328
51. Schenweiss S, Wang PS (2005) Claims data studies of sedative-hypnotics and hip fractures in older people: exploring residual confounding using survey information. J Am Geriatr Soc 53: 948–954
52. Avidan AY, Fries BE, James ML, Szafara KL, Wright GT, Chervin RD (2005) 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 53: 955–962
53. Barbera J, Shapiro CM (2005) Benefit-risk assessment of zaleplon in the treatment of insomnia. Drug Saf 28: 301–318
54. Ancoli-Israel S (2000) Insomnia in the elderly: a review for the primary care practitioner.
Sleep 23: S23–S30, discussion S36–S38
55. Allain H, Bentue-Ferre D, Tarral A, Gandon JM (2004) 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 59: 179–188
56. Linjakumpu TA, Hartikainen SA, Klaukka TJ, Koponen HJ, Hakko HH, Viilo KM, Haapea M, Kivela SL, Isoaho RE (2004) Sedative drug use in the home-dwelling elderly. Ann Pharmacother 38: 2017–2022
57. Kopanski Z, Sliwinska M, Piekoszewski W, Habiniak J, Wojewoda T, Wojewoda A, Schlegel-Zawadzka M, Sibiga W (2001) Endogenous diazepam concentrations in the serum of patients with liver neoplasms. Folia Histochem Cytobiol 39: 124–126 58. Gaillot J, Le Roux Y, Houghton GW, Dreyfus JF (1987) Critical factors for
pharmacoki-netics of zopiclone in the elderly and in patients with liver and renal insufficiency. Sleep 10: 7–21
59. Brodeur MR, Stirling AL (2001) Delirium associated with zolpidem. Ann Pharmacother 35: 1562–1564
60. Greenblatt DJ, Harmatz JS, Shapiro L, Engelhardt N, Gouthro TA, Shader RI (1991) Sensitivity to triazolam in elderly. New Engl J Med 324: 1691–1698
172 T.R. Shah, N.N. Trajanovic and C.M. Shapiro
61. Koda-Kimble MA, Young LY, Kradjan WA, Guglielmo B, Alldredge BK, Corelli RL (2004) Applied therapeutics: The clinical use of drugs, 8th edition. Lippincott Williams and Wilkins, Baltimore, 77.1–77.20
62. Glass JR, Sproule BA, Herrmann N, Streiner D, Busto UE (2003) Acute pharmacological effects of temazepam, diphenhydramine, and valerian in healthy elderly subjects. J Clin Psychopharmacol 23: 260–268
63. Antilla SA, Leinonen EV (2001) A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev 7: 249–264
64. Wingen M, Bothemer J, Langer S, Ramaekers JG (2005) Actual driving performance and psychomotor function in healthy subjects after acute and subchronic treatment with escitalopram, mirtazapine, and placebo: a crossover trial. J Clin Psychiatry 66: 436–443 65. Ridout F, Meadows R, Johnsen S, Hindmarch I (2003) A placebo controlled investiga-tion into the effects of paroxetine and mirtazapine on measures related to car driving performance. Hum Psychopharmacol 18: 261–269
66. Onofrj M, Luciano AL, Thomas A, Jacono D, D’Andreamatteo G (2003) Mirtazapine induces REM sleep behavior disorder (RBD) in Parkinsonism. Neurology 60: 113–115 67. Mendelson WB (2005) A review of the evidence for the efficacy and safety of trazodone
in insomnia. J Clin Psychiatry 66: 469–476
68. Kaynak H, Kaynak D, Gozukirmizi F, Guilleminault C (2004) The effects of trazodone on sleep in patients treated with stimulant antidepressants. Sleep Med 5: 15–20 69. Johnson EO, Roehrs T, Roth T, Breslau N (1998) Epidemiology of alcohol and medication
as aids to sleep in early adulthood. Sleep 21: 178–186
70. Neubauer DN (1999) Sleep problems in the elderly. Am Fam Physician 59: 2551–2558 71. Trendwalder C, Hundemer H-P, Lledo A, Swieca J, Polo O, Wetter TC, Ferini-Strambi L,
Groen H, Quail D, Brandenburg U (2004) The PEARLS study–Efficacy of pergolide in treatment of restless legs syndrome. Neurology 62: 1391–1397
72. Happe S, Klosch G, Saletu B, Zeitlhofer J (2001) Treatment of idiopathic restless legs syndrome with gabapentin. Neurology 57: 1717–1719
73. Lavigne GJ, Montplaisir JY (1994) Restless legs syndrome and sleep bruxism: prevalence and association among Canadians. Sleep 17: 739–743
74. Hornyak M, Trenkwalder C (2004) Restless legs syndrome and periodic limb movement disorder in the elderly. J Psychosom Res 56: 543–548
75. Chaudhri KR, Appiah-kubi LS, Trenkwalder C (2001) Restless legs syndrome. J Neurol Neurosurg Psychiatry 71: 143–146
76. Chokroverty S (2003) Editor’s corner: restless legs syndrome, a common disease uncom-monly diagnosed. Sleep Medicine 4: 91–93
77. Trenkwalder C, Paulus W, Walters A (2005) The restless legs syndrome. Lancet Neurology 4: 465–475
78. Walters AS, Winklemann J, Trenkwalder C, Fry JM, Kataria V, Wagner M, Sharma R, Hening W, Li L (2001) Long-term follow up on restless legs syndrome patients treated with opioids. Movement disorders 16: 1105–1109
79. Grewal M, Hawa R, Shapiro CM (2002) Treatment of periodic limb movements in sleep with selegiline HCL. Movement disorders 17: 398–401
80. Shapiro CM, Ohayon M, Huterer N, Grunstein R (2005) Fighting fatigue and sleepiness.
Practical strategies for minimizing sleepiness and fatigue. Joli joco publications Inc., Ontario
81. Shapiro CM, Dement WC (1993) ABC of sleep disorders. Impact and epidemiology of sleep disorders. BMJ 306: 1604–1607
82. Shapiro CM, Devins GM, Hussain MR (1993) ABC of sleep disorders. Sleep problems in patients with medical illness. BMJ 306: 1532–1535
Clinical Pharmacology of Sleep
Edited by S.R. Pandi-Perumal and J.M. Monti
“2006 Birkh ¨auser Verlag/Switzerland