Polypharmacy

Polypharmacy is most commonly defined as the use of five or more medications daily by an individual.[1] However, the definition of polypharmacy is still debated and can vary from two to 11 concurrent medications.[1] Some studies also generally define polypharmacy as the use of multiple concurrent medications or simultaneous long term use of different drugs by the same individual.[1]

The prevalence of polypharmacy is estimated to be between 10% and 90% depending on the definition used, the age group studied, and the geographic location.[2] Polypharmacy continues to grow in importance because of aging populations. Many countries are experiencing a fast growth of the older population, 65 years and older.[3][4][5] This growth is a result of the baby-boomer generation getting older and an increased life expectancy as a result of ongoing improvement in health care services worldwide.[6][7] About 21% of adults with intellectual disability are also exposed to polypharmacy.[8] There can be appropriate or inappropriate use of polypharmacy.[1]

Polypharmacy is not necessarily ill-advised, but in many instances can lead to negative outcomes or poor treatment effectiveness, often being more harmful than helpful or presenting too much risk for too little benefit. Therefore, health professionals consider it a situation that requires monitoring and review to validate whether all of the medications are still necessary. Concerns about polypharmacy include increased adverse drug reactions, drug interactions, prescribing cascade, and higher costs.[9] Polypharmacy is often associated with a decreased quality of life, including decreased mobility and cognition.[10]

Whether or not the advantages of polypharmacy (over taking single medications or monotherapy) outweigh the disadvantages or risks depends upon the particular combination and diagnosis involved in any given case.[11] The use of multiple drugs, even in fairly straightforward illnesses, is not an indicator of poor treatment and is not necessarily overmedication. Moreover, it is well accepted in pharmacology that it is impossible to accurately predict the side effects or clinical effects of a combination of drugs without studying that particular combination of drugs in test subjects. Knowledge of the pharmacologic profiles of the individual drugs in question does not assure accurate prediction of the side effects of combinations of those drugs; and effects also vary among individuals because of genome-specific pharmacokinetics. Therefore, deciding whether and how to reduce a list of medications (deprescribe) is often not simple and requires the experience and judgment of a practicing physician. However, such thoughtful and wise review is an ideal that too often does not happen, owing to problems such as poorly handled care transitions (poor continuity of care, usually because of siloed information), overworked physicians, and interventionism.

Appropriate medical uses

While polypharmacy is typically regarded as undesirable, prescription of multiple medications can be appropriate and therapeutically beneficial in some circumstances.[12] “Appropriate polypharmacy” is described as prescribing for complex or multiple conditions in such a way that necessary medicines are used according to best evidence to preserve safety and well-being.[12] Polypharmacy is clinically indicated in some conditions, including diabetes mellitus, but should be discontinued when evidence of benefit from the prescribed drugs no longer outweighs potential for harm (described below in Contraindications).[12]

Often certain medications can interact with others in a positive way specifically intended when prescribed together, to achieve a greater effect than any of the single agents alone. This is particularly prominent in the field of anesthesia and pain management – where atypical agents such as antiepileptics, antidepressants, muscle relaxants, NMDA antagonists, and other medications are combined with more typical analgesics such as opioids, prostaglandin inhibitors, NSAIDS and others. This practice of pain management drug synergy is known as an analgesia sparing effect.

Examples

Special Populations

People who are at greatest risk for negative polypharmacy consequences include elderly people, people with psychiatric conditions, people taking five or more drugs at the same time, those with multiple physicians and pharmacies, people who have been recently hospitalized, people who have concurrent comorbidities,[14] people who have a low educational level,[15] and those with impaired vision or dexterity.

It is not uncommon for people who are dependent or addicted to substances to enter or remain in a state of polypharmacy misuse. Note, however, that the term polypharmacy and its variants generally refer to legal drug use as-prescribed, even when used in a negative or critical context.

Measures can be taken to limit polypharmacy to its truly legitimate and appropriate needs. This is an emerging area of research, frequently called deprescribing.[16] This reduction in medications has been shown to reduce the number of medications and is safe as it does not significantly alter health outcomes.[17] Clinical pharmacists can perform drug therapy reviews and teach physicians and their patients about drug safety and polypharmacy, as well as collaborating with physicians and patients to correct polypharmacy problems. Similar programs are likely to reduce the potentially deleterious consequences of polypharmacy. Such programs hinge upon patients and doctors informing pharmacists of other medications being prescribed, as well as herbal, over-the-counter substances and supplements that occasionally interfere with prescription-only medication.

Risks of polypharmacy

The use of polypharmacy is correlated to the use of potentially inappropriate medications. Potentially inappropriate medications are generally taken to mean those that have been agreed upon by expert consensus, such as by the Beers Criteria. These medications are generally inappropriate for older adults because the risks outweigh the benefits. Examples of these include urinary anticholinergics, which can prevent up to one episode of incontinence every 48 hours on average. However, they can also cause constipation, dry eyes, dry mouth, impaired cognition, and increase the risk of falls.

Polypharmacy is associated with an increased risk of falls in elderly people.[18][19] Certain medications are well known to be associated with the risk of falls, including cardiovascular and psychoactive medications.[20][21] There is some evidence that the risk of falls increases cumulatively with the number of medications.[22][23] Although often not practical to achieve, withdrawing all medicines associated with falls risk can halve an individual's risk of future falls.

Every medication has potential adverse side-effects. With every drug added, there is an additive risk of side-effects. Also, some medications have interactions with other substances, including foods, other medications, and herbal supplements.[24] 15% of older adults are potentially at risk for a major drug-drug interaction.[25] Older adults are at a higher risk for a drug-drug interaction due to the increased number of medications prescribed and metabolic changes that occur with aging.[26] When a new drug is prescribed, the risk of interactions increases exponentially. Doctors and pharmacists aim to avoid prescribing medications that interact; often, adjustments in the dose of medications need to be made to avoid interactions. For example, warfarin interacts with many medications and supplements that can cause it to lose its effect.[26][27]

Pill burden

Pill burden is the number of pills (tablets or capsules, the most common dosage forms) that a person takes on a regular basis, along with all associated efforts that increase with that number - like storing, organizing, consuming, and understanding the various medications in one's regimen. The use of individual medications is growing faster than pill burden.[28]

Poor medical adherence is a common challenge among individuals who have increased pill burden and are subject to polypharmacy.[29] It also increases the possibility of adverse medication reactions (side effects) and drug-drug interactions. High pill burden has also been associated with an increased risk of hospitalization, medication errors, and increased costs for both the pharmaceuticals themselves and for the treatment of adverse events. Finally, pill burden is a source of dissatisfaction for many patients.

High pill burden was commonly associated with antiretroviral drug regimens to control HIV,[30] and is also seen in other patient populations.[31] For instance, adults with multiple common chronic conditions such as diabetes, hypertension, lymphedema, hypercholesterolemia, osteoporosis, constipation, inflammatory bowel disease, and clinical depression can often be prescribed more than a dozen different medications daily.[32] The combination of multiple drugs has been associated with an increased risk of adverse drug events.[33]

Reducing pill burden is recognized as a way to improve medication compliance. This is done through "deprescribing", where the risks and benefits are weighed when considering whether to continue a medication.[34] This includes drugs such as bisphosphonates (for osteoporosis) where it is often used indefinitely although there is only evidence to use it for five to ten years.[34] The use of memory tricks has also been seen to improve adherence and reduce pill burden in several countries.[26] These include associating medications with mealtimes, recording the dosage on the box, storing the medication in a special place, leaving it in plain sight in the living room, or putting the prescription sheet on the refrigerator.[26] The development of applications has also shown some benefit in this regard.[26] The use of a polypill regimen as opposed to a multi-pill regiment also alleviates pill burden and increases adherence.[29]

The selection of long-acting active ingredients over short-acting ones may also reduce pill burden. For instance, ACE inhibitors are used in the management of hypertension. Both captopril and lisinopril are examples of ACE inhibitors. However, lisinopril is dosed once a day, whereas captopril may be dosed 2-3 times a day. Assuming that there are no contraindications or potential for drug interactions, using lisinopril instead of captopril may be an appropriate way to limit pill burden.

Interventions

The most common intervention to help people who are struggling with polypharmacy is deprescribing.[35] Deprescribing refers to reducing the number of medications that a person is prescribed and includes the identification and discontinuance of medications when the benefit no longer outweighs the harm.[36] In elderly patients, this can commonly be done as a patient becomes more frail and treatment focus needs to shift from preventative to palliative.[36] Deprescribing was also deemed feasible and effective in other settings such as residential care, communities and hospitals.[35] This preventative measure should be considered for anyone who exhibits one of the following: (1) a new symptom or adverse event arises, (2) when the person develops an end-stage disease, (3) if the combination of drugs is risky, or (4) if stopping the drug does not alter the disease trajectory.[37]

Several tools exist to help physicians decide when to deprescribe and what medications can be added to a pharmaceutical regimen. The Beers Criteria and the STOPP/START criteria help identify medications that have the highest risk of adverse drug events (ADE) and drug-drug interactions.[38] The Medication appropriateness tool for comorbid health conditions during dementia (MATCH-D) is the only tool available specifically for people with dementia, and also cautions against polypharmacy and complex medication regimens.[39][40]

Barriers faced by both physicians and people taking the medications have made it challenging to apply deprescribing strategies in practice.[41] For physicians, these include fear of consequences of deprescribing, the prescriber's own confidence in their skills and knowledge to deprescribe, the feasibility of deprescribing, and the complexity of having multiple providers.[41][42] For people who are prescribed or require the medication, barriers include attitudes or beliefs about the medications, fears and uncertainties surrounding deprescribing, and influence of physicians, family, and the media are also reported barriers to deprescribing.[41]

The effectiveness of specific interventions to improve the appropriate use of polypharmacy such as pharmaceutical care and computerised decision support is unclear.[43] This is due to low quality of current evidence surrounding these interventions.[43] High quality evidence is needed to make any conclusions about the effects of such interventions in care homes.[44] Deprescribing rounds has been proposed as a potentially successful methodology in reducing polypharmacy.[45]

See also

References

  1. 1 2 3 4 Masnoon, Nashwa; Shakib, Sepehr; Kalisch-Ellett, Lisa; Caughey, Gillian E. (October 2017). "What is polypharmacy? A systematic review of definitions". BMC Geriatrics. 17 (1): 230. doi:10.1186/s12877-017-0621-2. ISSN 1471-2318. PMC 5635569. PMID 29017448.
  2. ↑ Khezrian, Mina; McNeil, Chris J.; Murray, Alison D.; Myint, Phyo K. (2020). "An overview of prevalence, determinants and health outcomes of polypharmacy". Therapeutic Advances in Drug Safety. 11: 2042098620933741. doi:10.1177/2042098620933741. ISSN 2042-0986. PMC 7294476. PMID 32587680.
  3. ↑ Cruz LP, Miranda PM, Vedana KG, Miasso AI (2011). "Medication therapy: adherence, knowledge and difficulties of elderly people from bipolar disorder" (PDF). Revista Latino-Americana de Enfermagem. 19 (4): 944–52. doi:10.1590/S0104-11692011000400013. PMID 21876947.
  4. ↑ Gellad WF, Grenard JL, Marcum ZA (February 2011). "A systematic review of barriers to medication adherence in the elderly: looking beyond cost and regimen complexity". The American Journal of Geriatric Pharmacotherapy. 9 (1): 11–23. doi:10.1016/j.amjopharm.2011.02.004. PMC 3084587. PMID 21459305.
  5. ↑ Page AT, Falster MO, Litchfield M, Pearson SA, Etherton-Beer C (July 2019). "Polypharmacy among older Australians, 2006-2017: a population-based study". The Medical Journal of Australia. 211 (2): 71–75. doi:10.5694/mja2.50244. PMID 31219179.
  6. ↑ Cline CM, Björck-Linné AK, Israelsson BY, Willenheimer RB, Erhardt LR (June 1999). "Non-compliance and knowledge of prescribed medication in elderly patients with heart failure". European Journal of Heart Failure. 1 (2): 145–9. doi:10.1016/S1388-9842(99)00014-8. PMID 10937924. S2CID 32043403.
  7. ↑ Yasein NA, Barghouti FF, Irshaid YM, Suleiman AA (March 2013). "Discrepancies between elderly patient's self-reported and prescribed medications: a social investigation". Scandinavian Journal of Caring Sciences. 27 (1): 131–8. doi:10.1111/j.1471-6712.2012.01012.x. PMID 22616831.
  8. ↑ Haider SI, Ansari Z, Vaughan L, Matters H, Emerson E (November 2014). "Prevalence and factors associated with polypharmacy in Victorian adults with intellectual disability". Research in Developmental Disabilities. 35 (11): 3071–80. doi:10.1016/j.ridd.2014.07.060. PMID 25129201.
  9. ↑ Haider SI, Johnell K, Weitoft GR, Thorslund M, Fastbom J (January 2009). "The influence of educational level on polypharmacy and inappropriate drug use: a register-based study of more than 600,000 older people". Journal of the American Geriatrics Society. 57 (1): 62–9. doi:10.1111/j.1532-5415.2008.02040.x. PMID 19054196. S2CID 205703844.
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  12. 1 2 3 Duerden, Martin (November 2013). Polypharmacy and medicines optimisation : making it safe and sound. Avery, Tony,, Payne, Rupert,, King's Fund (London, England). London. ISBN 978-1-909029-18-7. OCLC 864790728.
  13. ↑ Sergi G, De Rui M, Sarti S, Manzato E (July 2011). "Polypharmacy in the elderly: can comprehensive geriatric assessment reduce inappropriate medication use?". Drugs & Aging. 28 (7): 509–18. doi:10.2165/11592010-000000000-00000. PMID 21721596. S2CID 28551158.
  14. ↑ Boyd CM, Darer J, Boult C, Fried LP, Boult L, Wu AW (August 2005). "Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance". JAMA. 294 (6): 716–24. doi:10.1001/jama.294.6.716. PMID 16091574.
  15. ↑ Haider SI, Johnell K, Thorslund M, Fastbom J (February 2008). "Analysis of the association between polypharmacy and socioeconomic position among elderly aged > or =77 years in Sweden". Clinical Therapeutics. 30 (2): 419–27. doi:10.1016/j.clinthera.2008.02.010. PMID 18343279.
  16. ↑ Page AT, Clifford RM, Potter K, Schwartz D, Etherton-Beer CD (September 2016). "The feasibility and effect of deprescribing in older adults on mortality and health: a systematic review and meta-analysis". British Journal of Clinical Pharmacology. 82 (3): 583–623. doi:10.1111/bcp.12975. PMC 5338123. PMID 27077231.
  17. ↑ Potter K, Flicker L, Page A, Etherton-Beer C (4 March 2016). "Deprescribing in Frail Older People: A Randomised Controlled Trial". PLOS ONE. 11 (3): e0149984. Bibcode:2016PLoSO..1149984P. doi:10.1371/journal.pone.0149984. PMC 4778763. PMID 26942907.
  18. ↑ WHO global report on falls prevention in older age. World Health Organization. Ageing and Life Course Unit. Geneva, Switzerland: World Health Organization. 2008. ISBN 978-92-4-156353-6. OCLC 226291980.{{cite book}}: CS1 maint: others (link)
  19. ↑ Seniors' falls in Canada. Second report. Public Health Agency of Canada. Ottawa, ON. 2014. ISBN 978-1-100-23261-4. OCLC 1031268452.{{cite book}}: CS1 maint: others (link)
  20. ↑ Park, Hyerim; Satoh, Hiroki; Miki, Akiko; Urushihara, Hisashi; Sawada, Yasufumi (2015). "Medications associated with falls in older people: systematic review of publications from a recent 5-year period". European Journal of Clinical Pharmacology. 71 (12): 1429–1440. doi:10.1007/s00228-015-1955-3. ISSN 0031-6970. PMID 26407688. S2CID 44942.
  21. ↑ de Vries, Max; Seppala, Lotta J.; Daams, Joost G.; van de Glind, Esther M.M.; Masud, Tahir; van der Velde, Nathalie; Blain, Hubert; Bousquet, Jean; Bucht, Gösta; Caballero-Mora, Maria Angeles; van der Cammen, Tischa (2018). "Fall-Risk-Increasing Drugs: A Systematic Review and Meta-Analysis: I. Cardiovascular Drugs". Journal of the American Medical Directors Association. 19 (4): 371.e1–371.e9. doi:10.1016/j.jamda.2017.12.013. PMID 29396189.
  22. ↑ Zia, Anam; Kamaruzzaman, Shahrul Bahyah; Tan, Maw Pin (2015-05-04). "Polypharmacy and falls in older people: Balancing evidence-based medicine against falls risk". Postgraduate Medicine. 127 (3): 330–337. doi:10.1080/00325481.2014.996112. ISSN 0032-5481. PMID 25539567. S2CID 23910834.
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  29. 1 2 Baumgartner, Ana; Drame, Katarina; Geutjens, Stijn; Airaksinen, Marja (2020-02-22). "Does the Polypill Improve Patient Adherence Compared to Its Individual Formulations? A Systematic Review". Pharmaceutics. 12 (2): 190. doi:10.3390/pharmaceutics12020190. ISSN 1999-4923. PMC 7076630. PMID 32098393.
  30. ↑ Paramesha, Arjunahalli Eswarachar; Chacko, Leena Kunnath (2019). "Predictors of adherence to antiretroviral therapy among PLHIV". Indian Journal of Public Health. 63 (4): 367–376. doi:10.4103/ijph.IJPH_376_18. ISSN 0019-557X. PMID 32189660. S2CID 209445305.
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  32. ↑ Ha, Christina Y. (2014-02-01). "Medical Management of Inflammatory Bowel Disease in the Elderly: Balancing Safety and Efficacy". Clinics in Geriatric Medicine. 30 (1): 67–78. doi:10.1016/j.cger.2013.10.007. ISSN 0749-0690. PMID 24267603.
  33. ↑ Maher, Robert L.; Hanlon, Joseph; Hajjar, Emily R. (January 2014). "Clinical consequences of polypharmacy in elderly". Expert Opinion on Drug Safety. 13 (1): 57–65. doi:10.1517/14740338.2013.827660. ISSN 1744-764X. PMC 3864987. PMID 24073682.
  34. 1 2 Hilmer SN, Gnjidic D, Le Couteur DG (December 2012). "Thinking through the medication list - appropriate prescribing and deprescribing in robust and frail older patients". Australian Family Physician. 41 (12): 924–8. PMID 23210113.
  35. 1 2 Page, Amy T.; Clifford, Rhonda M.; Potter, Kathleen; Schwartz, Darren; Etherton‐Beer, Christopher D. (2016). "The feasibility and effect of deprescribing in older adults on mortality and health: a systematic review and meta‐analysis". British Journal of Clinical Pharmacology. 82 (3): 583–623. doi:10.1111/bcp.12975. ISSN 0306-5251. PMC 5338123. PMID 27077231.
  36. 1 2 Cadogan CA, Ryan C, Hughes CM (February 2016). "Appropriate Polypharmacy and Medicine Safety: When Many is not Too Many". Drug Safety. 39 (2): 109–16. doi:10.1007/s40264-015-0378-5. PMC 4735229. PMID 26692396.
  37. ↑ Rankin, Audrey; Cadogan, Cathal A; Patterson, Susan M; Kerse, Ngaire; Cardwell, Chris R; Bradley, Marie C; Ryan, Cristin; Hughes, Carmel (2018-09-03). Cochrane Effective Practice and Organisation of Care Group (ed.). "Interventions to improve the appropriate use of polypharmacy for older people". Cochrane Database of Systematic Reviews. 2018 (9): CD008165. doi:10.1002/14651858.CD008165.pub4. PMC 6513645. PMID 30175841.
  38. ↑ Campanelli, Christine M. (2012). "American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults". Journal of the American Geriatrics Society. 60 (4): 616–631. doi:10.1111/j.1532-5415.2012.03923.x. ISSN 0002-8614. PMC 3571677. PMID 22376048.
  39. ↑ "MATCH-D Medication Appropriateness Tool for Comorbid Health conditions during Dementia".
  40. ↑ Page AT, Potter K, Clifford R, McLachlan AJ, Etherton-Beer C (October 2016). "Medication appropriateness tool for co-morbid health conditions in dementia: consensus recommendations from a multidisciplinary expert panel". Internal Medicine Journal. 46 (10): 1189–1197. doi:10.1111/imj.13215. PMC 5129475. PMID 27527376.
  41. 1 2 3 Reeve, Emily; Thompson, Wade; Farrell, Barbara (2017). "Deprescribing: A narrative review of the evidence and practical recommendations for recognizing opportunities and taking action". European Journal of Internal Medicine. 38: 3–11. doi:10.1016/j.ejim.2016.12.021. ISSN 1879-0828. PMID 28063660.
  42. ↑ Anderson, Kristen; Stowasser, Danielle; Freeman, Christopher; Scott, Ian (2014-12-08). "Prescriber barriers and enablers to minimising potentially inappropriate medications in adults: a systematic review and thematic synthesis". BMJ Open. 4 (12): e006544. doi:10.1136/bmjopen-2014-006544. ISSN 2044-6055. PMC 4265124. PMID 25488097.
  43. 1 2 Rankin, Audrey; Cadogan, Cathal A.; Patterson, Susan M.; Kerse, Ngaire; Cardwell, Chris R.; Bradley, Marie C.; Ryan, Cristin; Hughes, Carmel (2018). "Interventions to improve the appropriate use of polypharmacy for older people". The Cochrane Database of Systematic Reviews. 2018 (9): CD008165. doi:10.1002/14651858.CD008165.pub4. ISSN 1469-493X. PMC 6513645. PMID 30175841.
  44. ↑ Alldred DP, Kennedy MC, Hughes C, Chen TF, Miller P (February 2016). "Interventions to optimise prescribing for older people in care homes". The Cochrane Database of Systematic Reviews. 2: CD009095. arXiv:1510.02343. doi:10.1002/14651858.CD009095.pub3. PMC 7111425. PMID 26866421.
  45. ↑ Edey R, Edwards N, Von Sychowski J, Bains A, Spence J, Martinusen D (February 2019). "Impact of deprescribing rounds on discharge prescriptions: an interventional trial". International Journal of Clinical Pharmacy. 41 (1): 159–166. doi:10.1007/s11096-018-0753-2. PMID 30478496. S2CID 53730423.

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