The feasibility and effect of deprescribing in older adults on mortality and health: a systematic review and meta-analysis

British Journal of Clinical Pharmacology

Volumn , Issue , 2016, Pages 583-623

  Page, Amy T ^a   Clifford, Rhonda M ^a   Potter, Kathleen ^a   Schwartz, Darren ^a,c   Etherton Beer, Christopher D ^a,b  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^b ROYAL PERTH HOSPITAL   (Australia)

^c GRAYLANDS HOSPITAL   (Australia)

Author keywords

deprescribing; medication discontinuation; meta analysis; older adults; polypharmacy; systematic review

Indexed keywords

AGED; COGNITION; DEMENTIA; DEPRESCRIPTION; DRUG USE; FEASIBILITY STUDY; GENERAL PRACTICE; GERIATRIC CARE; HEALTH CARE NEED; HUMAN; META ANALYSIS; MORTALITY; OUTCOME ASSESSMENT; POLYPHARMACY; PRESCRIPTION; PRIORITY JOURNAL; QUALITY OF LIFE; REVIEW; SYSTEMATIC REVIEW;

EID: 84982883655     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/bcp.12975     Document Type: Review

References (178)

1. Marengoni A, Angleman S, Melis R, Mangialasche F, Karp A, Garmen A, et al. Aging with multimorbidity: a systematic review of the literature. Ageing Res Rev 2011; 10: 430–9.
2. Mills EJ, Rachlis B, Wu P, Devereaux PJ, Arora P, Perri D. Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients. J Am Coll Cardiol 2008; 52: 1769–81.
3. Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 2009; 373: 2125–35.
4. Wald DS, Law M, Morris JK, Bestwick JP, Wald NJ. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med 2009; 122: 290–300.
5. Roehrborn CG, Siami P, Barkin J, Damião R, Major-Walker K, Nandy I, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol 2010; 57: 123–31.
6. Hubbard RE, Peel NM, Scott IA, Martin JH, Smith A, Pillans PI, et al. Polypharmacy among inpatients aged 70 years or older in Australia. Med J Aust 2015; 202: 373–8.
7. Linjakumpu T, Hartikainen S, Klaukka T, Veijola J, Kivelä SL, Isoaho R. Use of medications and polypharmacy are increasing among the elderly. J Clin Epidemiol 2002; 55: 809–17.
8. Guthrie B, Makubate B, Hernandez-Santiago V, Dreischulte T. The rising tide of polypharmacy and drug–drug interactions: population database analysis 1995–2010. BMC Med 2015; 13: 74.
9. Hovstadius B, Hovstadius K, Åstrand B, Petersson G. Increasing polypharmacy – an individual-based study of the Swedish population 2005–2008. BMC Clin Pharmacol 2010; 10: 16.
10. Turner JP, Jamsen KM, Shakib S, Singhal N, Prowse R, Bell JS. Polypharmacy cut-points in older people with cancer: how many medications are too many? Support Care Cancer 2016; 24: 1831–40.
11. Gnjidic D, Hilmer SN, Blyth FM, Naganathan V, Waite L, Seibel MJ, et al. Polypharmacy cutoff and outcomes: five or more medicines were used to identify community-dwelling older men at risk of different adverse outcomes. J Clin Epidemiol 2012; 65: 989–95.
12. Huizer-Pajkos A, Kane AE, Howlett SE, Mach J, Mitchell SJ, de Cabo R, et al. Adverse geriatric outcomes secondary to polypharmacy in a mouse model: the influence of aging. J Gerontol A Biol Sci Med Sci 2016; 71: 571–7.
13. Jyrkkä J, Enlund H, Korhonen MJ, Sulkava R, Hartikainen S. Polypharmacy status as an indicator of mortality in an elderly population. Drugs Aging 2009; 26: 1039–48.
14. Scott IA, Hilmer SN, Reeve E, Potter K, Le Couteur D, Rigby D, et al. Reducing inappropriate polypharmacy: the process of deprescribing. JAMA Intern Med 2015; 175: 827–34.
15. Reeve E, Gnjidic D, Long J, Hilmer S. A systematic review of the emerging definition of ‘deprescribing’ with network analysis: implications for future research and clinical practice. Br J Clin Pharmacol 2015; 80: 1254–68.
16. Scott IA, Le Couteur David G. Physicians need to take the lead in deprescribing. Intern Med J 2015; 45: 352–6.
17. Anderson K, Stowasser D, Freeman C, Scott I. Prescriber barriers and enablers to minimising potentially inappropriate medications in adults: a systematic review and thematic synthesis. BMJ Open 2014; 4: e006544.
18. Reeve E, To J, Hendrix I, Shakib S, Roberts MS, Wiese MD. Patient barriers to and enablers of deprescribing: a systematic review. Drugs Aging 2013; 30: 793–807.
19. Declercq T, Petrovic M, Azermai M, Vander Stichele R, De Sutter A, van Driel ML, et al. Withdrawal versus continuation of chronic antipsychotic drugs for behavioural and psychological symptoms in older people with dementia. Cochrane Database Syst Rev 2013; 3: CD007726.
20. Iyer S, Naganathan V, McLachlan AJ, Le Conteur DG. Medication withdrawal trials in people aged 65 years and older. Drugs Aging 2008; 25: 1021–31.
21. Pollmann AS, Murphy AL, Bergman JC, Gardner DM. Deprescribing benzodiazepines and Z-drugs in community-dwelling adults: a scoping review. BMC Pharmacol Toxicol 2015; 16: 19.
22. Gillespie LD, Robertson MC, Gillespie WJ, Lamb SE, Gates S, Cumming RG, et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev 2009; 2: CD007146.
23. Lindsay J, Dooley M, Martin J, Fay M, Kearney A, Barras M. Reducing potentially inappropriate medications in palliative cancer patients: evidence to support deprescribing approaches. Support Care Cancer 2014; 22: 1113–9.
24. Page A, Khalil H, Etherton-Beer C, Clifford R, Potter K. The efficacy of deprescribing interventions on health outcomes in people aged over 65 years: a systematic review protocol. PROSPERO 2014; CRD42014009887. Available at http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014009887
25. Page AT, Khalil H, Etherton-Beer C, Clifford R, Potter K. The efficacy of deprescribing interventions on health outcomes in people aged over 65 years: a systematic review protocol. JBI Database Syst Rev Implementation Rep 2014; 12: 124–34.
26. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2700.
27. Distiller SREvidence Partners Inc, 2010. Available at: https://distillercer.com/products/distillersr-systematic-review-software/ (accessed May 3, 2016).
28. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928.
29. Higgins J. Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane Collaboration 2011; 5.
30. Cochrane Collaboration. Review Manager (RevMan). 5.3. Copenhagen: The Nordic Cochrane Centre, 2014.
31. Adams SG, Anzueto A, Briggs DD Jr, Leimer I, Kesten S. Evaluation of withdrawal of maintenance tiotropium in COPD. Respir Med 2009; 103: 1415–20.
32. Allard J, Hebert R, Asselin J, Voyer L. Efficacy of a clinical medication review on the number of potentially inappropriate prescriptions prescribed for community-dwelling elderly people. Can Med Assoc J 2001; 164: 1291–6.
33. Alsop K, Mac Mahon M. Withdrawing cardiovascular medications at a syncope clinic. Postgrad Med J 2001; 77: 403–5.
34. Azermai M, Petrovic M, Engelborghs S, Elseviers MM, Van der Mussele S, Debruyne H, et al. The effects of abrupt antipsychotic discontinuation in cognitively impaired older persons: a pilot study. Aging Ment Health 2013; 17: 125–32.
35. Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K, et al. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet Neurol 2009; 8: 151–7.
36. Ballard C, Margallo Lana M, Theodoulou M, Douglas S, McShane R, Jacoby R, et al. A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial). PLoS Med 2008; 5: e76.
37. Ballard C, Thomas A, Fossey J, Lee L, Jacoby R, Lana M, et al. A 3-month, randomized, placebo-controlled, neuroleptic discontinuation study in 100 people with dementia: the neuropsychiatric inventory median cutoff is a predictor of clinical outcome. J Clin Psychiatry 2004; 65: 114–9.
38. Beer C, Potter K, Loh PK, Peng YG, Millar A. A pilot randomized controlled trial of deprescribing: Stopat (Systematic Termination of Pharmaceutical Agents Trial). Basic Clin Pharmacol Toxicol 2011; 109: 156.
39. Bergh S, Engedal K. The withdrawal of antipsychotics and antidepressants from patients with dementia and BPSD living in nursing homes – an open pilot study. Int J Geriatr Psychiatry 2008; 23: 877–9.
40. Bergh S, Selbaek G, Engedal K. Discontinuation of antidepressants in people with dementia and neuropsychiatric symptoms (DESEP study): double blind, randomised, parallel group, placebo controlled trial. BMJ 2012; 344: e1566.
41. Black DM, Reid IR, Boonen S, Bucci-Rechtweg C, Cauley JA, Cosman F, et al. The effect of 3 versus 6 years of Zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 2012; 27: 243–54.
42. Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, et al. Effects of continuing or stopping alendronate after 5 years of treatment – the Fracture Intervention Trial long-term extension (FLEX): A randomized trial. JAMA 2006; 296: 2927–38.
43. Borrill Z, Roy K, Kolsum U, Southworth T, Vestbo J, Singh D. Seretide withdrawal increases airway inflammation in moderate COPD patients. Eur J Clin Pharmacol 2009; 65: 1165–6.
44. Bourgeois J, Elseviers MM, Van Bortel L, Petrovic M, Vander Stichele RH. Feasibility of discontinuing chronic benzodiazepine use in nursing home residents: a pilot study. Eur J Clin Pharmacol 2014; 70: 1251–60.
45. Bridges-Parlet S, Knopman D, Steffes S. Withdrawal of neuroleptic medications from institutionalized dementia patients: results of a double-blind, baseline-treatment-controlled pilot study. J Geriatr Psychiatry Neurol 1997; 10: 119–26.
46. Burr ML, King S, Davies HE, Pathy MS. The effects of discontinuing long-term diuretic therapy in the elderly. Age Ageing 1977; 6: 38–45.
47. Campbell AJ, Robertson MC, Gardner MM, Norton RN, Buchner DM. Psychotropic medication withdrawal and a home-based exercise program to prevent falls: a randomized, controlled trial. J Am Geriatr Soc 1999; 47: 850–3.
48. Choudhury AB, Dawson CM, Kilvington HE, Eldridge S, James WY, Wedzicha JA, et al. Withdrawal of inhaled corticosteroids in people with COPD in primary care: a randomised controlled trial. Respir Res 2007; 8: 93.
49. Cibere J, Kopec JA, Thorne A, Singer J, Canvin J, Robinson DB, et al. Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis. Arthritis Rheum 2004; 51: 738–45.
50. Cohen-Mansfield J, Lipson S, Werner P, Billig N, Taylor L, Woosley R. Withdrawal of haloperidol, thioridazine, and lorazepam in the nursing home: a controlled, double-blind study. Arch Intern Med 1999; 159: 1733–40.
51. Coll PP, Abourizk NN. Successful withdrawal of thyroid hormone therapy in nursing home patients. J Am Board Fam Pract 2000; 13: 403–7.
52. Cunnington AL, White L, Hood K. Identification of possible risk factors for the development of dopamine agonist withdrawal syndrome in Parkinson's disease. Parkinsonism Relat Disord 2012; 18: 1051–2.
53. Curran HV, Collins R, Fletcher S, Kee SCY, Woods B, Iliffe S. Older adults and withdrawal from benzodiazepine hypnotics in general practice: effects on cognitive function, sleep, mood and quality of life. Psychol Med 2003; 33: 1223–37.
54. da Silva AG, Vieira JGH, Kunii IS, de Lana JM, Lazaretti-Castro M. The effects of discontinuing long term alendronate therapy in a clinical practice setting. Arq Bras Endocrinol Metabol 2011; 55: 272–8.
55. Dalleur O, Boland B, Losseau C, Henrard S, Wouters D, Speybroeck N, et al. Reduction of potentially inappropriate medications using the STOPP criteria in frail older inpatients: a randomised controlled study. Drugs Aging 2014; 31: 291–8.
56. Daly C, Edwards H. Withdrawal of digoxin in general practice in elderly patients. Ir Med J 1983; 76: 19–20.
57. Dawson DL, De Maioribus CA, Hagino RT, Light JT, Bradley DVJ, Britt KE, et al. The effect of withdrawal of drugs treating intermittent claudication. Am J Surg 1999; 178: 141–6.
58. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women. Am J Clin Nutr 2000; 72: 745–50.
59. De Jonge JW, Knottnerus JA, Van Zutphen WM, De Bruijne GA, Struijker Boudier HAJ. Short term effect of withdrawal of diuretic drugs prescribed for ankle oedema. BMJ 1994; 308: 511–3.
60. Derogar M, Sandblom G, Lundell L, Orsini N, Bottai M, Lu Y, et al. Discontinuation of low-dose aspirin therapy after peptic ulcer bleeding increases risk of death and acute cardiovascular events. Clin Gastroenterol Hepatol 2013; 11: 38–42.
61. Devanand DP. Relapse risk after discontinuation of risperidone in Alzheimer's disease. N Engl J Med 2012; 367: 2458.
62. Devanand DP, Mintzer J, Schultz SK, Andrews HF, Sultzer DL, de la Pena D, et al. Relapse risk after discontinuation of risperidone in Alzheimer's disease. N Engl J Med 2012; 367: 1497–507.
63. Devanand DP, Pelton GH, Cunqueiro K, Sackeim HA, Marder K. A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation trial following response to haloperidol treatment of psychosis and agitation in Alzheimer's disease. Int J Geriatr Psychiatry 2011; 26: 937–43.
64. Drimer T, Shahal B, Barak Y. Effects of discontinuation of long-term anticholinergic treatment in elderly schizophrenia patients. Int Clin Psychopharmacol 2004; 19: 27–9.
65. Eastell R, Hannon RA, Wenderoth D, Rodriguez-Moreno J, Sawicki A. Effect of stopping risedronate after long-term treatment on bone turnover. J Clin Endocrinol Metab 2011; 96: 3367–73.
66. Ekbom T, Lindholm LH, Oden A, Dahlof B, Hansson L, Westers PO, et al. A 5-year prospective, observational study of the withdrawal of antihypertensive treatment in elderly people. J Intern Med 1994; 235: 581–8.
67. Ensrud KE, Barrett-Connor EL, Schwartz A, Santora AC, Bauer DC, Suryawanshi S, et al. Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD: results from the Fracture Intervention Trial long-term extension. J Bone Miner Res 2004; 19: 1259–69.
68. Espeland MA, Whelton PK, Kostis JB, Bahnson JL, Ettinger WH, Cutler JA, et al. Predictors and mediators of successful long-term withdrawal from antihypertensive medications. Arch Fam Med 1999; 8: 228–36.
69. Esselinckx W, Doherty SM, Dixon ASJ. Polymyalgia rheumatica – abrupt and gradual withdrawal of prednisolone treatment, clinical and laboratory observations. Ann Rheum Dis 1977; 36: 219–24.
70. Fahy S, Lawlor B. Discontinuation of lithium augmentation in an elderly cohort. Int J Geriatr Psychiatry 2001; 16: 1004–9.
71. Fair JF. Supervised withdrawal of long-term digoxin therapy. Fam Pract 1990; 7: 56–9.
72. Fernandez H, Trieschmann M, Okun MS. Rebound psychosis: effect of discontinuation of antipsychotics in Parkinson's disease. Mov Disord 2005; 20: 104–5.
73. Flint AJ, Rifat SL. Recurrence of first-episode geriatric depression after discontinuation of maintenance. Am J Psychiatry 1999; 156: 943.
74. Fonrose HA, Ahlbaum N, Bugatch E, Cohen M, Genovese C, Kelly J. The efficacy of digitalis withdrawal in an institutional aged population. J Am Geriatr Soc 1974; 22: 208–11.
75. Fotherby MD, Potter JF. Possibilities for antihypertensive drug therapy withdrawal in the elderly. J Hum Hypertens 1994; 8: 857–63.
76. Gallagher JC, Rapuri PB, Haynatzki G, Detter JR. Effect of discontinuation of estrogen, calcitriol, and the combination of both on bone density and bone markers. J Clin Endocrinol Metab 2002; 87: 4914–23.
77. Gallagher PF, O'Connor MN, O'Mahony D. Prevention of potentially inappropriate prescribing for elderly patients: a randomized controlled trial using STOPP/START criteria. Clin Pharmacol Ther 2011; 89: 845–54.
78. García-Gollarte F, Baleriola-Júlvez J, Ferrero-López I, Cuenllas-Díaz Á, Cruz-Jentoft AJ. An educational intervention on drug use in nursing homes improves health outcomes resource utilization and reduces inappropriate drug prescription. J Am Med Dir Assoc 2014; 15: 885–91.
79. Garfinkel D, Mangin D. Feasibility study of a systematic approach for discontinuation of multiple medications in older adults addressing polypharmacy. Arch Intern Med 2010; 170: 1648–54.
80. Garfinkel D, Zur-Gil S, Ben-Israel J. The war against polypharmacy: a new cost-effective geriatric-palliative approach for improving drug therapy in disabled elderly people. Isr Med Assoc J 2007; 9: 430–4.
81. Gaudig M, Richarz U, Han J, Van Baelen B, Schauble B. Effects of galantamine in Alzheimer's disease: double-blind withdrawal studies evaluating sustained versus interrupted treatment. Curr Alzheimer Res 2011; 8: 771–80.
82. George J, Kitzis I, Zandorf D, Golovner M, Shapira I, Laniado S, et al. Safety of nitrate withdrawal in angina-free and hemodynamically stable patients with coronary artery disease. Chest 2003; 124: 1652–7.
83. Gerety MB, Cornell JE, Plichta DT, Eimer M. Adverse events related to drugs and drug withdrawal in nursing home residents. J Am Geriatr Soc 1993; 41: 1326–32.
84. Gnjidic D, Le Couteur DG, Abernethy DR, Hilmer SN. A pilot randomized clinical trial utilizing the drug burden index to reduce exposure to anticholinergic and sedative medications in older people. Ann Pharmacother 2010; 44: 1725–32.
85. Graves T, Hanlon JT, Schmaler KE, Landsman PB, Samsa GP, Pieper CF, et al. Adverse events after discontinuing medications in elderly outpatients. Arch Intern Med 1997; 157: 2205–10.
86. Habraken H, Soenen K, Blondeel L, Van Elsen J, Bourda J, Coppens E, et al. Gradual withdrawal from benzodiazepines in residents of homes for the elderly: experience and suggestions for future research. Eur J Clin Pharmacol 1997; 51: 355–8.
87. Hajjar I, Hart M, Wan S-H, Novak V. Safety and blood pressure trajectory of short-term withdrawal of antihypertensive medications in older adults: experience from a clinical trial sample. J Am Soc Hypertens 2013; 7: 289–93.
88. Hanlon JT, Weinberger M, Samsa GP, Schmader KE, Uttech KM, Lewis IK, et al. A randomized controlled trial of a clinical pharmacist intervention with elderly outpatients with polypharmacy. Am J Med 1996; 100: 428–37.
89. Hansen AG, Jensen H, Laugesen LP, Petersen A. Withdrawal of antihypertensive drugs in the elderly. Acta Med Scand 1983; 214: 178–85.
90. Hardy BG, Shulman KI, Zucchero C. Gradual discontinuation of lithium augmentation in elderly patients with unipolar depression. J Clin Psychopharmacol 1997; 17: 22–6.
91. Hauser RA, Koller WC, Hubble JP, Malapira T, Busenbark K, Olanow CW. Time course of loss of clinical benefit following withdrawal of levodopa/carbidopa and bromocriptine in early Parkinson's disease. Mov Disord 2000; 15: 485–9.
92. Hearing SD, Wesnes KA, Bowman CE. Beta blockers and cognitive function in elderly hypertensive patients: withdrawal and consequences of ACE inhibitor substitution. Int J Geriatr Psychopharmacol 1999; 2: 13–7.
93. Henschke PJ, Spence JD, Cape RDT. Diuretics and the institutional elderly – a case against routine potassium prescribing. J Am Geriatr Soc 1981; 29: 145–50.
94. Horwitz GJ, Tariot PN, Mead K, Cox C. Discontinuation of antipsychotics in nursing home patients with dementia. Am J Geriatr Psychiatry 1995; 3: 290–9.
95. Jackson G, Martin E, McGing E, Cooper A. Successful withdrawal of oral long-acting nitrates to facilitate phosphodiesterase type 5 inhibitor use in stable coronary disease patients with erectile dysfunction. J Sex Med 2005; 2: 513–6.
96. Jampel HD, Chon BH, Stamper R, Packer M, Han Y, Nguyen QH, et al. Effectiveness of intraocular pressure-lowering medication determined by washout. JAMA Ophthalmol 2014; 132: 390–5.
97. Jarad NA, Wedzicha JA, Burge PS, Calverley PMA. An observational study of inhaled corticosteroid withdrawal in stable chronic obstructive pulmonary disease. Respir Med 1999; 93: 161–6.
98. Jiménez-Candil J, Bermejo J, Yotti R, Cortina C, Moreno M, Cantalapiedra JL, et al. Effects of angiotensin converting enzyme inhibitors in hypertensive patients with aortic valve stenosis: a drug withdrawal study. Heart 2005; 91: 1311–8.
99. Jondeau G, Neuder Y, Eicher JC, Jourdain P, Fauveau E, Galinier M, et al. B-CONVINCED: Beta-blocker CONtinuation Vs. INterruption in patients with Congestive heart failure hospitalizED for a decompensation episode. Eur Heart J 2009; 30: 2186–92.
100. Kostis JB, Espeland MA, Appel L, Johnson KC, Pierce J, Wofford JL. Does withdrawal of antihypertensive medication increase the risk of cardiovascular events? Trial of Nonpharmacologic Interventions in the Elderly (TONE) Cooperative Research Group. Am J Cardiol 1998; 82: 1501–8.
101. Kroenke LTCK, Pinholt EM. Reducing polypharmacy in the elderly. a controlled trial of physician feedback. J Am Geriatr Soc 1990; 38: 31–6.
102. Kutner JS, Blatchford P, Taylor D, Ritchie C, Bull J, Fairclough D, et al. Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial. JAMA Intern Med 2015; 175: 691–700.
103. Lähteenmäki R, Puustinen J, Vahlberg T, Lyles A, Neuvonen PJ, Partinen M, et al. Melatonin for sedative withdrawal in older patients with primary insomnia: a randomized double-blind placebo-controlled trial. Br J Clin Pharmacol 2014; 77: 975–85.
104. Leder BZ, Neer RM, Wyland JJ, Lee HW, Burnett-Bowie S-AM, Finkelstein JS. Effects of teriparatide treatment and discontinuation in postmenopausal women and eugonadal men with osteoporosis. J Clin Endocrinol Metabol 2009; 94: 2915–21.
105. Lernfelt B, Landahl S, Svanborg A, Wikstrand J. Overtreatment of hypertension in the elderly? J Hypertens 1990; 8: 483–90.
106. Lin VC-H, Liao C-H, Kuo H-C. Progression of lower urinary tract symptoms after discontinuation of 1 medication from 2-year combined alpha-blocker and 5-alpha-reductase inhibitor therapy for benign prostatic hyperplasia in men – a randomized multicenter study. Urology 2014; 83: 416–21.
107. Lindström K, Ekedahl A, Carlsten A, Mårtensson J, Mölstad S. Can selective serotonin inhibitor drugs in elderly patients in nursing homes be reduced? Scand J Prim Health Care 2007; 25: 3–8.
108. Macarthur C. Withdrawal of maintenance digoxin from institutionalized elderly. Postgrad Med J 1990; 66: 940–2.
109. Minett TSC, Thomas A, Wilkinson LM, Daniel SL, Sanders J, Richardson J, et al. What happens when donepezil is suddenly withdrawn? An open label trial in dementia with Lewy bodies and Parkinson's disease with dementia. Int J Geriatr Psychiatry 2003; 18: 988–93.
110. Moonen JE, Foster-Dingley JC, de Ruijter W, van der Grond J, Bertens AS, van Buchem MA, et al. Effect of discontinuation of antihypertensive treatment in elderly people on cognitive functioning – the DANTE Study Leiden: a randomized clinical trial. JAMA Intern Med 2015; 175: 1622–30.
111. Muir AJ, Sanders LL, Wilkinson WE, Schmader K. Reducing medication regimen complexity – a controlled trial. J Gen Intern Med 2001; 16: 77–82.
112. Myers MG, Weingert ME, Fisher RH, Gryfe CI, Shulman HS. Unnecessary diuretic therapy in the elderly. Age Ageing 1982; 11: 213–21.
113. Nadal M, Wikstrom L, Allgulander S. Once hypertensive, always hypertensive? A three year follow-up after stopping medication. Scand J Prim Health Care 1994; 12: 62–4.
114. Nelson MR, Reid CM, Krum H, Muir T, Ryan P, McNeil JJ. Predictors of normotension on withdrawal of antihypertensive drugs in elderly patients: prospective study in second Australian national blood pressure study cohort. BMJ 2002; 325: 815–7.
115. Nelson MR, Reid CM, Krum H, Ryan P, Wing LMH, McNeil JJ. Short-term predictors of maintenance of normotension after withdrawal of antihypertensive drugs in the Second Australian National Blood Pressure Study (ANBP2). Am J Hypertens 2003; 16: 39–45.
116. O'Brien A, Russo-Magno P, Karki A, Hiranniramol S, Hardin M, Kaszuba M, et al. Effects of withdrawal of inhaled steroids in men with severe irreversible airflow obstruction. Am J Respir Crit Care Med 2001; 164: 365–71.
117. OrrWalker B, Wattie DJ, Evans MC, Reid IR. Effects of prolonged bisphosphonate therapy and its discontinuation on bone mineral density in post-menopausal osteoporosis. Clin Endocrinol (Oxf) 1997; 46: 87–92.
118. Patel MR, Hellkamp AS, Lokhnygina Y, Piccini JP, Zhang Z, Mohanty S, et al. Outcomes of discontinuing rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: Analysis from the ROCKET AF trial (Rivaroxaban once-daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation). J Am Coll Cardiol 2013; 61: 651–8.
119. Petrovic M, Pevernagie D, Mariman A, Van Maele G, Afschrift M. Fast withdrawal from benzodiazepines in geriatric inpatients: a randomised double-blind, placebo-controlled trial. Eur J Clin Pharmacol 2002; 57: 759–64.
120. Pitkala KH, Juola A-L, Kautiainen H, Soini H, Finne-Soveri UH, Bell JS, et al. Education to reduce potentially harmful medication use among residents of assisted living facilities: a randomized controlled trial. J Am Med Dir Assoc 2014; 15: 892–8.
121. Pitkala KH, Juola A-L, Soini H, Laakkonen M-L, Kautiainen H, Teramura-Gronblad M, et al. Reducing inappropriate, anticholinergic and psychotropic drugs among older residents in assisted living facilities: study protocol for a randomized controlled trial. Trials 2012; 13: 85.
122. Pitkala KH, Strandberg TE, Tilvis RS. Is it possible to reduce polypharmacy in the elderly? A randomised, controlled trial. Drugs Aging 2001; 18: 143–9.
123. Potter K, Flicker L, Page A, Etherton-Beer CD. Deprescribing in frail older people: a randomised controlled trial. PLoS One 2016; 11: e0149984.
124. Puustinen J, Lahteenmaki R, Polo-Kantola P, Salo P, Vahlberg T, Lyles A, et al. Effect of withdrawal from long-term use of temazepam, zopiclone or zolpidem as hypnotic agents on cognition in older adults. Eur J Clin Pharmacol 2014; 70: 319–29.
125. Radford L, Bolland M, Mason B, Horne A, Gamble G, Grey A, et al. The Auckland calcium study: 5-year post-trial follow-up. Osteoporos Int 2014; 25: 297–304.
126. Reeve E, Andrews J, Wiese M, Hendrix I, Roberts M, Shakib S. Feasibility of a patient-centered deprescribing process to reduce inappropriate use of proton pump inhibitors. Ann Pharmacother 2015; 49: 29–38.
127. Reid IR, Wattie DJ, Evans MC, Gamble GD, Stapleton JP, Cornish J. Continuous therapy with pamidronate, a potent bisphosphonate, in postmenopausal osteoporosis. J Clin Endocrinol Metab 1994; 79: 1595–9.
128. Reitz CJ. Digoxin withdrawal in patients in sinus rhythm. S Afr Med J 1981; 60: 570.
129. Rice K, Rubins J, Lebahn F, Parenti C, Duane P, Kuskowski M, et al. Withdrawal of chronic systemic corticosteroids in patients with COPD – a randomized trial. Am J Respir Crit Care Med 2000; 162: 174–8.
130. Ruths S, Straand J, Anygaard H, Aarsland D. Stopping antipsychotic drug therapy in demented nursing home patients: a randomized, placebo-controlled study – The Bergen District Nursing Home Study (BEDNURS). Int J Geriatr Psychiatry 2008; 23: 889–95.
131. Ruths S, Straand J, Nygaard HA, Bjorvatn B, Pallesen S. Effect of antipsychotic withdrawal on behavior and sleep/wake activity in nursing home residents with dementia: a randomized, placebo-controlled, double-blinded study. The Bergen District Nursing Home Study. J Am Geriatr Soc 2004; 52: 1737–43.
132. Salonoja M, Salminen M, Vahlberg T, Aarnio P, Kivela SL. Withdrawal of psychotropic drugs decreases the risk of falls requiring treatment. Arch Gerontol Geriatr 2012; 54: 160–7.
133. Salzman C, Fisher J, Nobel K, Glassman R, Wolfson A, Kelley M. Cognitive improvement following benzodiazepine discontinuation in elderly nursing home residents. Int J Geriatr Psychiatry 1992; 7: 89–93.
134. Sambu N, Dent H, Englyst N, Warner TD, Leadbeater P, Roderick P, et al. Effect of clopidogrel withdrawal on platelet reactivity and vascular inflammatory biomarkers 1 year after drug-eluting stent implantation: results of the prospective, single-centre CESSATION study. Heart 2011; 97: 1661–7.
135. Scarpini E, Bruno G, Zappala G, Adami M, Richarz U, Gaudig M, et al. Cessation versus continuation of galantamine treatment after 12 months of therapy in patients with Alzheimer's disease: a randomized, double blind, placebo controlled withdrawal trial. J Alzheimers Dis 2011; 26: 211–20.
136. Schwartz AV, Bauer DC, Cummings SR, Cauley JA, Ensrud KE, Palermo L, et al. Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture: the FLEX trial. J Bone Miner Res 2010; 25: 976–82.
137. Sjöblom P, Anders T, Löfgren UB, Lannering C, Anderberg N, Rosenqvist U, et al. Can diabetes medication be reduced in elderly patients?: An observational study of diabetes drug withdrawal in nursing home patients with tight glycaemic control. Diabetes Res Clin Pract 2008; 82: 197–202.
138. Sjosten NM, Salonoja M, Piirtola M, Vahlberg T, Isoaho R, Hyttinen H, et al. A multifactorial fall prevention programme in home-dwelling elderly people: a randomized-controlled trial. Public Health 2007; 121: 308–18.
139. Somani S. Dyskinesias secondary to gradual neuroleptic drug withdrawal in elderly nursing home residents. J Geriatr Drug Ther 1996; 11: 37–51.
140. Sommers DK, Reitz CJ, Koch Z, Avenant JC. Digoxin withdrawal in patients with sinus rhythm. S Afr Med J 1981; 60: 239–40.
141. Straand J, Fugelli P, Laake K. Withdrawing long-term diuretic treatment among elderly patients in general practice. Fam Pract 1993; 10: 38–42.
142. Tabloski PA, Cooke KM, Thoman EB. A procedure for withdrawal of sleep medication in elderly women who have been long-term users. J Gerontol Nurs 1998; 24: 20–8.quiz 50–1
143. Tannenbaum C, Martin P, Tamblyn R, Benedetti A, Ahmed S. Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: the EMPOWER cluster randomized trial. JAMA Intern Med 2014; 174: 890–8.
144. Tariot PN, Jakimovich LJ, Erb R, Cox C, Lanning B, Irvine C, et al. Withdrawal from controlled carbamazepine therapy followed by further carbamazepine treatment in patients with dementia. J Clin Psychiatry 1999; 60: 684–9.
145. Tham TCK, Brown H, Taggart HM. Temazepam withdrawal in elderly hospitalized-patients – a double-blind randomized trial comparing abrupt versus gradual withdrawal. Ir J Med Sci 1989; 158: 294–6.
146. Thapa PB, Meador KG, Gideon P, Fought RL, Ray WA. Effects of antipsychotic withdrawal in elderly nursing home residents. J Am Geriatr Soc 1994; 42: 280–6.
147. Tse W, Frisina PG, Haelbit TD, Gracies JM, Liang L, Tarshish C, et al. The effects of withdrawal of dopaminergic medication in nursing home patients with advanced Parkinsonism. J Am Med Dir Assoc 2008; 9: 670–5.
148. Tsunoda K, Uchida H, Suzuki T, Watanabe K, Yamashima T, Kashima H. Effects of discontinuing benzodiazepine-derivative hypnotics on postural sway and cognitive functions in the elderly. Int J Geriatr Psychiatry 2010; 25: 1259–65.
149. Ulfvarson J, Adami J, Wredling R, Kjellman B, Reilly M, Von Bahr C. Controlled withdrawal of selective serotonin reuptake inhibitor drugs in elderly patients in nursing homes with no indication of depression. Eur J Clin Pharmacol 2003; 59: 735–40.
150. Van Der Velde N, Stricker BHC, Pols HAP, Van Der Cammen TJM. Risk of falls after withdrawal of fall-risk-increasing drugs: a prospective cohort study. Br J Clin Pharmacol 2007; 63: 232–7.
151. Van Der Velde N, Stricker BHC, Pols HAP, Van Der Cammen TJM. Withdrawal of fall-risk-increasing drugs in older persons: effect on mobility test outcomes. Drugs Aging 2007; 24: 691–9.
152. van Kraaij DJW, Jansen RWMM, Bouwels LHR, Gribnau FWJ, Hoefnagels WHL. Furosemide withdrawal in elderly heart failure patients with preserved left ventricular systolic function. Am J Cardiol 2000; 85: 1461–6.
153. van Kraaij DJW, Jansen RWMM, Bouwels LHR, Hoefnagels WHL. Furosemide withdrawal improves postprandial hypotension in elderly heart failure patients with preserved left ventricular systolic function. Arch Intern Med 1999; 159: 1599–605.
154. van Kraaij DJW, Jansen RWMM, Sweep FCGJ, Hoefnagels WHL. Neurohormonal effects of furosemide withdrawal in elderly heart failure patients with normal systolic function. Eur J Heart Fail 2003; 5: 47–53.
155. Van Reekum R, Clarke D, Conn D, Herrmann N, Eryavec G, Cohen T, et al. A randomized, placebo-controlled trial of the discontinuation of long-term antipsychotics in dementia. Int Psychogeriatr 2002; 14: 197–210.
156. Walma EP, Hoes AW, Prins A, Boukes FS, van der Does E. Withdrawing long-term diuretic therapy in the elderly: a study in general practice in The Netherlands. Fam Med 1993; 25: 661–4.
157. Walma EP, Hoes AW, van Dooren C, Prins A, van der Does E. Withdrawal of long term diuretic medication in elderly patients: a double blind randomised trial. BMJ 1997; 315: 464–8.
158. Watts NB, Chines A, Olszynski WP, McKeever CD, McClung MR, Zhou X, et al. Fracture risk remains reduced one year after discontinuation of risedronate. Osteoporos Int 2008; 19: 365–72.
159. Weber V, White A, McIlvried R. An electronic medical record (EMR)-based intervention to reduce polypharmacy and falls in an ambulatory rural elderly population. J Gen Intern Med 2008; 23: 399–404.
160. Wilkins CE, Khurana MS. Digitalis withdrawal in elderly nursing home patients. J Am Geriatr Soc 1985; 33: 850–1.
161. Yedidya I, Netzer A, Vaduganathan M, Solodky A, Kornowski R, Lev Eli I. Clopidogrel tapering as a strategy to attenuate platelet rebound phenomenon in patients with bare-metal stents. J Thromb Thrombolysis 2012; 33: 16–21.
162. Yeh YC, Liu CL, Peng LN, Lin MH, Chen LK. Potential benefits of reducing medication-related anticholinergic burden for demented older adults: a prospective cohort study. Geriatr Gerontol Int 2013; 13: 694–700.
163. Brodaty H. Halting Antipsychotic use in Long-Term Care (HALT). Sydney, Australia: Australian and New Zealand Clinical Trials Registry, 2014.
164. Etherton-Beer CD, Potter K, Hilmer Sarah N, Naganathan V, McLachlan A, Comans T, et al. Opti-Med: A randomised controlled trial of deprescribing to optimise health outcomes for frail older people. Crawley, Western Australia: Australian and New Zealand Clinical Trials Registry, 2013.
165. Wouters H, Quik E, Boersma F, Nygard P, Bosman J, Bottger W, et al. Discontinuing inappropriate medication in nursing home residents (DIM-NHR Study): protocol of a cluster randomised controlled trial. BMJ Open 2014; 10: e006082.
166. Hartholt KA, Van Der Velde N, Van Lieshout EM, Polinder S, De Vries OJ, Boyé ND, et al. [Cost]effectiveness of withdrawal of fall-risk increasing drugs versus conservative treatment in older fallers: design of a multicenter randomized controlled trial (IMPROveFALL-study). BMC Geriatr 2011; 11: 48.
167. Hasler S, Senn ORT, Neuner-Jehle S. Effect of a patient-centered drug review on polypharmacy in primary care patients: study protocol for a cluster-randomized controlled trial. Trials 2015; 16: 380.
168. Campbell AJ, Robertson MC, Gardner MM, Norton RN, Tilyard MW, Buchner DM. Randomised controlled trial of a general practice programme of home based exercise to prevent falls in elderly women. BMJ 1997; 315: 1065–9.
169. Eriksen EF, Diez-Perez A, Boonen S. Update on long-term treatment with bisphosphonates for postmenopausal osteoporosis: a systematic review. Bone 2014; 58: 126–35.
170. Goeres LM, Williams CD, Eckstrom E, Lee DS. Pharmacotherapy for hypertension in older adults: a systematic review. Drugs Aging 2014; 31: 897–910.
171. Holmes HM, Hayley DC, Alexander GC, Sachs GA. Reconsidering medication appropriateness for patients late in life. Arch Intern Med 2006; 166: 605–9.
172. Garfinkel D, Ilhan B, Bahat G. Routine deprescribing of chronic medications to combat polypharmacy. Ther Adv Drug Saf 2015; 6: 212–33.
173. Dalleur O, Boland B, De Groot A, Vaes B, Boeckxstaens P, Azermai M, et al. Detection of potentially inappropriate prescribing in the very old: cross-sectional analysis of the data from the BELFRAIL observational cohort study. BMC Geriatr 2015; 15: 1.
174. Page AT, Etherton-Beer CD, Clifford RM, Burrows S, Eames M, Potter K. Deprescribing in frail older people – do doctors and pharmacists agree? Res Social Adm Pharm 2016; 12: 438–49.
175. Gnjidic D, Le Couteur DG, Kouladjian L, Hilmer SN. Deprescribing trials: methods to reduce polypharmacy and the impact on prescribing and clinical outcomes. Clin Geriatr Med 2012; 28: 237–53.
176. Scott IA, Gray LC, Martin JH, Pillans PI, Mitchell CA. Deciding when to stop: towards evidence-based deprescribing of drugs in older populations. Evid Based Med 2013; 18: 121–4.
177. Scott IA, Anderson K, Freeman CR, Stowasser DA. First do no harm: a real need to deprescribe in older patients. Med J Aust 2014; 201: 390–2.
178. Hardy JE, Hilmer SN. Deprescribing in the last year of life. J Pharm Pract Res 2011; 41: 146–51.