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Drugs
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Deprescribing is the process of tapering, withdrawing, discontinuing or stopping medications to reduce polypharmacy, adverse drug effects and inappropriate or ineffective medication use. It involves re-evaluating the ongoing reasons for, and effectiveness of medication therapy. It is often applied for those with chronic conditions, for the elderly and for those who have a limited life expectancy. In all of these situations, polypharmacy can contribute to an increased risk of adverse events, and people may benefit from a reduction in medication use.

Deprescribing, when performed by medical professionals, can be effective in reducing medication burden in patients to improve quality of life while maintaining control of chronic conditions.[1] It must be done carefully with monitoring to avoid worsening of disease or withdrawal effects.

Why Deprescribe?[]

As people develop chronic diseases or age, there is often an increase in medication use. While prescribing medications is intended to improve patient health, it can sometimes cause problems. Polypharmacy is associated with increased risks of adverse drug events, drug interactions, falls, hospitalization, cognitive deficits [2] and mortality.[3] In light of this, optimizing patients’ medications through targeted deprescribing is a vital part of managing chronic conditions, avoiding adverse effects and improving outcomes.

Medications might be stopped if there is no evidence that they are working, if they are no longer needed or if they are causing harmful side effects.

Medications might be stopped if there is little clinical trial evidence for effectiveness of the particular drug in similar populations. For example, there are few medication trials in the very old so it is often hard to know how effective medications in this age group might be.[4]

Medications might be stopped if a person is not expected to live long enough to benefit.[5] Medications might be tapered or stopped as people age because the ability of the body to process medications changes with age; doses that were fine when younger can become too much with age. For the frail elderly, there is evidence that more lenient blood pressure,[6] blood sugar [7] and cholesterol [8] targets than those usually recommended for younger people are safe and effective. In these situations, targeted deprescribing could be used to minimize drug-related side effects.

Examples of deprescribing in such a population could include tapering or stopping: a) a diuretic to reduce the possibility of too low blood pressure, dizziness and falls, b) a statin in a frail elderly patient experiencing muscle pain, c) a diabetes therapy to reduce the likelihood of low blood sugar.

Evidence for the Impact of Deprescribing[]

By deprescribing medications, prescribers are often able to improve patient function, generate a higher quality of life and reduce bothersome signs and symptoms. For example, targeted deprescribing can improve cognition in the elderly while also improving adherence to other drugs.[1] Deprescribing has also been linked to lower fall risk and global improvements in health.[1][9] Deprescribing can also reduce the complexity of medication schedules. This complexity is a known barrier for patients trying to adhere to prescribed therapies.[10]

A systematic review conducted by Iyer et al. in 2008 summarized studies in which specific medications were stopped to detect benefits and risks in the elderly. The researchers found 31 studies involving 8972 patients. These studies evaluated deprescribing for a wide range of medications including diuretics, blood pressure medication, sedatives, antidepressants, benzodiazepines and nitrates. The authors concluded that adverse effects were not often seen during the deprescribing process and if they appeared, they were easily dealt with by recommencing the medication. Depending on the study, between 20 to 85% of patients who had their blood pressure medication gradually tapered remained at normal blood pressure levels. Other studies showed that stopping psychotropic medications resulted in less falls for patients and enhanced mental function.[11] However, these studies were small, not of high methodological quality and sometimes limited by exclusion criteria (e.g. didn’t include the sickest patients).

Garfinkel et al used a deprescribing algorithm to guide decisions regarding whether a drug should be stopped, the dose reduced or left as-is.[9] For example, the authors stopped nitrates in patients who had not experienced heart symptoms for three months, H2 blockers were stopped for patients without ulcer or stomach conditions, supplements were stopped for patients whose blood levels were within the normal limits and blood pressure medications were stopped if the patient’s readings were within the range accepted by medical guidelines [9] The algorithm was tested on 119 geriatric patients with medications stopped successfully 82% of the time. The group that underwent the deprescribing process had a 24% lower mortality compared to a control group with 71 patients. There was also a significant decrease in specialist referral rate and cost of drugs.[9] In a second study in 2010, the deprescribing algorithm was used with 70 patients; 81% of discontinuations were successful while 88% of patients reported global improvement in health.[12]

Risks of Deprescribing - Adverse Drug Withdrawal Events (ADWE)[]

When deprescribing, it is possible for the patient to develop signs and symptoms known as adverse drug withdrawal events (ADWE).[13] These symptoms may be related to the original reason why the medication was prescribed, or they might be new experiences for the patient. Medications may mask underlying diseases and by removing them, there is a possibility for the signs and symptoms of such diseases to appear. It is also possible that the patient’s body becomes accustomed to the medication and when it is stopped, withdrawal symptoms or other symptoms develop. Withdrawal is particularly common when abruptly stopping medications that act on the nervous system, such as benzodiazepines or antidepressants.[14] ADWEs can generally be minimized or avoided by tapering the dose slowly and carefully monitoring for symptoms. Prescribers should be aware of which medications require tapering and which can be safely stopped suddenly. People should never abruptly stop a medication without working with the prescriber (See Table - Drugs That Often Cause ADWEs).

File:Drugs that often cause ADWE, Deprescribing.pdf

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[13]

Approaches to Deprescribing[]

Once the need to stop a drug has been recognized, it is important to try to reduce or stop one medication at time, determine whether to taper or stop and check for benefit or harm as each medication is stopped.

Taper vs. Stop?[]

Prescribers need to decide whether to abruptly stop a medication or slowly taper (reduce the dose) over a period of weeks or months. Pharmacists are helpful in determining whether a drug requires tapering or can be safely stopped abruptly. Working together, prescribers and pharmacists can develop and implement a detailed plan for deprescribing and monitoring.

Medications should ideally be tapered (dose reduced slowly over time) if they are associated with adverse drug withdrawal events. Medications may also be tapered to address the psychosocial needs of the patient, especially if the medication has been used on a chronic basis or the patient has become attached to its use.[15] Prescribing medication is seen as an act of caring by the prescriber;[16] therefore the benefits of deprescribing must be explained clearly to avoid assumptions of inferior care or deteriorating conditions.[15]

Examples of medications that should be tapered (not stopped abruptly) include: [14][17] Alpha-blockers, anticonvulsants, antidepressants, antihypertensives, antipsychotics, benzodiazepines, beta-blockers, corticosteroids, hormones, laxatives, lithium, nitrates, opioids

Examples of medications that are not associated with adverse drug withdrawal events include: ASA, bisphosphonates, calcium, docusate, fibrates, glucosamine, iron, vitamins

The following approaches are useful for prescribers to determine if a drug should be tapered or can be abruptly stopped:

  • Find out if the patient is actually taking the medication. Often, patients may have already stopped the drug and there is no need to taper the dose if they are not taking it.[14]
  • Ask the patient if he or she has ever tried to stop taking the medication in the past. What happened?
  • Do a literature review to see if there are deprescribing studies that have examined the impact of stopping the particular medication. In the studies, was the drug stopped abruptly or tapered? What did the researchers monitor? [14]
  • Medications with long half-lives (the time required for the body to remove half of the drug from circulation) may not need to be tapered. For example, long half-life benzodiazepines can be abruptly stopped while tapering short half-life benzodiazepines reduces the severity of withdrawal symptoms.

Monitoring[]

Deprescribing requires detailed follow-up and monitoring, not unlike the attention required when starting a new medication. It is recommended that prescribers frequently monitor “relevant signs, symptom, laboratory or diagnostic tests that were the original indications for starting the medication” as well as for potential withdrawal effects.[12] Please see "Deprescribing Monitoring Protocols" [18][19][20][21][22][23][24][25][26][27][28]

File:Deprescribing Monitoring Protocols.pdf

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Helpful Tools[]

Several tools have been published to make prescribers aware of inappropriate medications for patient groups. For example, Beers Criteria and the STOPP/Start criteria alert prescribers to medications that may be inappropriate for use in the elderly. RxFiles, an academic detailing group based in Saskatchewan, Canada, has developed a tool to help long-term care providers identify potentially inappropriate medications in their residents.[(RxFiles Link http://www.rxfiles.ca/rxfiles/Modules/ltc/ltc.aspx)]

In “A Practical Guide to Stopping Medications in Older People”, The Best Practice Journal of New Zealand provides both considerations for stopping a medication, as well as examples of approaches. [1]

The Canadian Medical Association Journal has also published a table to guide clinicians on how to prioritize patients in order to identify appropriate candidates for deprescribing. [2] [16]

Barriers to Deprescribing[]

Although many trials have successfully resulted in a reduction in medication use, there are some known barriers to deprescribing. Physicians interviewed about deprescribing felt medications were overused in the elderly but they were not always comfortable or confident in discontinuing chronic medications.[29] They identified barriers to deprescribing as: lack of evidence for continuing or discontinuing medications for disease prevention among elderly patients, discomfort explaining to patients that medications can be withdrawn because the benefit of drug therapy is no longer clear with declining life expectancy, discomfort with not following guidelines recommending specific drug therapies, not wishing to stop medications started by another physician and patients believing continued medication therapy is needed.

Summary[]

Medication use should be re-assessed and monitored regularly. Medications should not always be started for indefinite use, but instead started with deprescribing criteria in mind. There should be a plan to deprescribe the drug once it is no longer needed, has been shown to not be effective or is causing a possible side effect. Health care professionals must incorporate medication reviews into patient interactions. If a medication is identified that does not have an indication, an attempt should be made to proactively deprescribe it prior to an adverse drug event.

“Simply because a patient has tolerated a therapy for a long duration does not mean that it remains an appropriate treatment. Thoughtful review of a patient’s medication regimen in the context of any changes in medical status and potential future benefits should occur regularly, and those agents that may no longer be necessary should be considered for a trial of medication discontinuation.” Ref - Linsky A, Simon SR, JAMA 2013 [30]

In the future, more research of high methodological quality examining the effects of deprescribing would help with developing guidelines for tapering and monitoring medications.

See also[]

Other Literature[]

  • Optimizing drug treatment for elderly people: the prescribing cascade (BMJ [3]
  • Thinking through the medication list – Appropriate prescribing and deprescribing in robust and frail older patients [4]
  • A practical guide to stopping medicines in older people [5]
  • Reversing Gears: Discontinuing Medication Therapy to Prevent Adverse Events (JAMA 2013) [6]
  • Prioritizing and stopping medicines (CMAJ, 2006) [7]
  • Deprescribing: Achieving Better Health Outcomes for Older People Through Reducing Medications (Geriatric Therapeutics, 2003) [8]
  • STOPP / Start Criteria for Medication Use in the Elderly [9]

References[]

  1. 1.0 1.1 1.2 Gnjidic D, Le Couteur DG, Kouladjian L, Hilmer SN. Deprescribing trials: methods to reduce polypharmacy and the impact on prescribing and clinical outcomes. ClinGeriatr Med 2012;28:237–253.
  2. Cao YJ, et al.Physical and cognitive performance and burden of anticholinergics, sedatives, and ACE inhibitors in older women. Clinical Pharmacology and Therapeutics 2008, 83:422-429
  3. Hajjar ER, Cafiero AC, Hanlon JT. Polypharmacy in elderly patients. Am J GeriatrPharmacother 2007;5(4):345-351
  4. Hilmer SN, Gnjidic D, Le Couteur DG. Thinking through the medication list - appropriate prescribing and deprescribing in robust and frail older patients. Aust Fam Physician. 2012 Dec;41(12):924-8.
  5. Lee SP, Bain KT, Maio V. Appropriate discontinuation of medications at the end of life: a need to establish consensus criteria. Am J Med Qual. 2007;22 (6):393-394.
  6. Sabayan B, Oleksik AM, Maier AB, van Buchem MA, Poortvliet RK, de Ruijter W, Gussekloo J, de Craen AJ, Westendorp RG.. High Blood Pressure and Resilience to Physical and Cognitive Decline in the Oldest Old: The Leiden 85-Plus Study. J Am Geriatr Soc 60:2014–2019, 2012.
  7. Kirkman SM, Briscoe VJ, Clark N, Florez H, Haas LB, Halter JB, Huang ES, Korytkowski MT, Munshi MN, Odegard PS, Pratley RE, Swift CS;Consensus Development Conference on Diabetes and Older Adults. Diabetes in older adults: a consensus report. J Am Geriatr Soc. 2012 Dec;60(12):2342-56. doi: 10.1111/jgs.12035. Epub 2012 Oct 25.
  8. Petersen LK, Christensen K, Kragstrup J. Lipid lowering treatment to the end? A review of observational studies and RCTs on cholesterol and mortality in 80+-year olds. Age and Ageing 2010; 39: 674–680 doi: 10.1093/ageing/afq129
  9. 9.0 9.1 9.2 9.3 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. IMAJ 2007;9:430–34.Hardy JE, Hilmer SN.
  10. Hilmer SN, McLachlan AJ, Le Couteur DG. Clinical Pharmacology in the Geriatric Patient. Fundam Clin Pharmacol. 2007 Jun;21(3):217-30.
  11. Iyer S, Naganathan V, McLachlan AJ, Le Couteur DG. Medication withdrawal trials in people aged 65 years and older: a systematic review. Drugs Aging 2008;25(12): 1021-31.
  12. 12.0 12.1 Garfinkel D, Mangin D. Feasibility study of a systematic approach for discontinuation of multiple medications in older adults. Arch Intern Med. 2010;170(18):1648-54.
  13. 13.0 13.1 Graves T, Hanlon JT, Schmader KE, Landsman PB, Samsa GP, Pieper CF, Weinberger M. Adverse events after discontinuing medications in elderly outpatients. Arch Intern Med. 1997 Oct 27;157(19):2205-10.
  14. 14.0 14.1 14.2 14.3 Woodward MC. Deprescribing: Achieving better health outcomes for older people through reducing medications. J Pharm Pract Res 2003;33:323–328.
  15. 15.0 15.1 Bain KT, Holmes HM, Beers MH, Maio V, Handler SM, Pauker SG. Discontinuing medications: a novel approach for revising the prescribing stage of the medication-use process. J Am Geriatr Soc. 2008 Oct;56(10):1946-52. doi: 10.1111/j.1532-5415.2008.01916.x
  16. 16.0 16.1 Alexander GC, Sayla MA, Holmes HM, Sachs GA. Prioritizing and stopping prescription medicines. CMAJ. 2006 Apr 11;174(8):1083-4.
  17. Common oral medications that may need tapering. Pharmacist’s Letter/Prescriber’s Letter 2008;24(12):241208
  18. Nelson MR, Reid CM, Krum H, et al. Predictors of normotension on withdrawal of antihypertensive drugs in elderly patients: prospective study in second Australian National Blood - Pressure Study cohort. BMJ 2002; 325: 815-9.
  19. 19. Straand J, Fugelli P, Laake K. Withdrawing long-term diuretic treatment among elderly patients in general practice. Fam Pract 1993;10:38-42.
  20. Cohen-Mansfield J, Lipson S, Werner, P, et al. Withdrawal of haloperidol, thioridazine, and lorazepam in the nursing home. Arch Intern Med 1999;159:1733-40.
  21. Fair JF. Supervised withdrawal of long-term digoxin therapy. Fam Pract 1990; 7: 56-9.
  22. Choudhury AB, Dawson CM, Kilvington HE. Withdrawal of inhaled corticosteroids in people with COPD in primary care: a randomised controlled trial. Resp Res 2007;8(93):1-12.
  23. 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.
  24. Campbell AJ, Robertson MC, Gardner MM, et al. Psychotropic medication withdrawal and a home-based exercise program to prevent falls: a randomized, controlled trial. J Am Geriatr Soc 1999; 47: 850-3.
  25. van der Velde N, Stricker BH, Huib AP, Tischa JM. Risk of falls after withdrawal of fall-risk-increasing drugs: a prospective cohort study. Br J Clin Pharmacol 2007;63(2):232-37.
  26. Björnsson E, Abrahamsson H, Simrén M, Mattsson N, Jensen C, Agerforz P, Kilander A. Discontinuation of proton pump inhibitors in patients on long-term therapy: a double-blind, placebo-controlled trial. Aliment Pharmacol Ther. 2006 Sep 15;24(6):945-54.
  27. Zarowitz BJ. The challenge of discontinuing proton pump inhibitors. Geriatr Nurs. 2011 Jul-Aug;32(4):276-8. doi: 10.1016/j.gerinurse.2011.06.002
  28. Black DM, Schwartz AV, Ensrud KE, et al. Effects of continuing or stopping alendronate after 5 years of treatment. JAMA 2006;296:2927-38.
  29. Schuling J, Gebben H, Veehof LJG, Haaijer-Ruskamp FM. Deprescribing medication in very elderly patients with multimorbidity: the view of Dutch GPs. A qualitative study. BMC Family Practice 2012; 13:56-62.
  30. Linsky A, Simon SR. Reversing Gears: Discontinuing Medication Therapy to Prevent Adverse Events: Comment on "Proton Pump Inhibitors and Risk of 1-Year Mortality and Rehospitalization in Older Patients Discharged From Acute Care Hospitals" JAMA Intern Med. 2013 Mar 4:1-2. doi: 10.1001/jamainternmed.2013.4068. [Epub ahead of print]