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Current Neurology and Neuroscience Reports

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31-07-2023 | Multiple Sclerosis

Polypharmacy in Multiple Sclerosis: Prevalence, Risks, and Mitigation Strategies

Authors: W. Daniel Chapman, Megan C. Herink, Michelle H. Cameron, Dennis Bourdette

Published in: Current Neurology and Neuroscience Reports | Issue 9/2023

Abstract

Purpose of Review

Polypharmacy, the use of ≥ 5 medications, is common in people with multiple sclerosis and is associated with negative outcomes. The use of multiple medications is common for symptom management in people with multiple sclerosis, but risks drug-drug interactions and additive side effects. Multiple sclerosis providers should therefore focus on the appropriateness and risks versus benefits of pharmacotherapy in each patient. This review describes the prevalence and risks associated with polypharmacy in people with multiple sclerosis and offers strategies to identify and mitigate inappropriate polypharmacy.

Recent Findings

Research in people with multiple sclerosis has identified risk factors and negative outcomes associated with polypharmacy. Medication class-specific investigations highlight their contribution to potentially inappropriate polypharmacy in people with multiple sclerosis.

Summary

People with multiple sclerosis are at risk for inappropriate polypharmacy. Multiple sclerosis providers should review medications and consider their appropriateness and potential for deprescribing within the context of each patient.

Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017;17(1):230. https://doi.org/10.1186/s12877-017-0621-2.CrossRefPubMedPubMedCentral

Reeve E, Thompson W, Farrell B. Deprescribing: A narrative review of the evidence and practical recommendations for recognizing opportunities and taking action. Eur J Intern Med. 2017;38:3–11. https://doi.org/10.1016/j.ejim.2016.12.021.CrossRefPubMed

Boyd C, Smith CD, Masoudi FA, Blaum CS, Dodson JA, Green AR, et al. Decision Making for Older Adults With Multiple Chronic Conditions: Executive Summary for the American Geriatrics Society Guiding Principles on the Care of Older Adults With Multimorbidity. J Am Geriatr Soc. 2019;67(4):665–73. https://doi.org/10.1111/jgs.15809.CrossRefPubMed

Halli-Tierney AD, Scarbrough C, Carroll D. Polypharmacy: Evaluating Risks and Deprescribing. Am Fam Physician. 2019;100(1):32–8.PubMed

Young EH, Pan S, Yap AG, Reveles KR, Bhakta K. Polypharmacy prevalence in older adults seen in United States physician offices from 2009 to 2016. PloS One. 2021;16(8):e0255642. https://doi.org/10.1371/journal.pone.0255642.CrossRefPubMedPubMedCentral

• Delara M, Murray L, Jafari B, Bahji A, Goodarzi Z, Kirkham J, et al. Prevalence and factors associated with polypharmacy: a systematic review and Meta-analysis. BMC Geriatr. 2022;22(1):601. https://doi.org/10.1186/s12877-022-03279-x. This systematic review and meta-analysis evaluated the pooled prevalence of polypharmacy and factors associated with polypharmacy.CrossRefPubMedPubMedCentral

Fried TR, O’Leary J, Towle V, Goldstein MK, Trentalange M, Martin DK. Health outcomes associated with polypharmacy in community-dwelling older adults: a systematic review. J Am Geriatr Soc. 2014;62(12):2261–72. https://doi.org/10.1111/jgs.13153.CrossRefPubMedPubMedCentral

Canio WC. Polypharmacy in Older Adults. Clin Geriatr Med. 2022;38(4):621–5. https://doi.org/10.1016/j.cger.2022.05.004.CrossRefPubMed

Pazan F, Wehling M. Polypharmacy in older adults: a narrative review of definitions, epidemiology and consequences. Eur Geriatr Med. 2021;12(3):443–52. https://doi.org/10.1007/s41999-021-00479-3.CrossRefPubMedPubMedCentral

10.

Leelakanok N, Holcombe AL, Lund BC, Gu X, Schweizer ML. 2017 Association between polypharmacy and death: A systematic review and meta-analysis. J Am Pharm Assoc. 2003;57(6):729-38.e10. https://doi.org/10.1016/j.japh.2017.06.002.CrossRef

11.

Hovstadius B, Petersson G. Factors leading to excessive polypharmacy. Clin Geriatr Med. 2012;28(2):159–72. https://doi.org/10.1016/j.cger.2012.01.001.CrossRefPubMed

12.

Medication Safety in Polypharmacy. Geneva: World Health Organization; 2019 (WHO/UHC/SDS/2019.11). Licence: CC BY-NC-SA 3.0 IGO.

13.

American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052–81.

14.

O’Mahony D, O’Sullivan D, Byrne S, O’Connor MN, Ryan C, Gallagher P. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing. 2015;44(2):213–8. https://doi.org/10.1093/ageing/afu145.CrossRefPubMed

15.

•• Monette PJ, Schwartz AW. Optimizing Medications with the Geriatrics 5Ms: An Age-Friendly Approach. Drugs Aging. 2023;40(5):391–6. This paper presents a framework for addressing polypharmacy and optimizing medication use in geriatric patients.

16.

Frahm N, Hecker M, Zettl UK. Polypharmacy in Chronic Neurological Diseases: Multiple Sclerosis, Dementia and Parkinson’s Disease. Curr Pharm Des. 2021;27(38):4008–16. https://doi.org/10.2174/1381612827666210728102832.CrossRefPubMed

17.

Rojanasarot S, Carlson A. Health Care Utilization Associated With Polypharmacy In Patients With Multiple Sclerosis. Value in Health. 2017;20(9):A513.CrossRef

18.

• de Oliveira VM, Rios CC, Gubert VT, Ferreira CM, de Vasconcelos-Pereira EF, Toffoli-Kadri MC, Monreal MTFD. Association of clinical epidemiological factors to polypharmacy among patients with multiple sclerosis: real-life data. ABCS Health Sciences. 2021;46:e021212–e021212. https://doi.org/10.7322/abcshs.2020137. ()CrossRef

19.

Bachmann P, Frahm N, Debus JL, Mashhadiakbar P, Langhorst SE, Streckenbach B, et al. Prevalence and Severity of Potential Drug-Drug Interactions in Patients with Multiple Sclerosis with and without Polypharmacy. Pharmaceutics. 2022;14(3):592. https://doi.org/10.3390/pharmaceutics14030592.CrossRefPubMedPubMedCentral

20.

Frahm N, Hecker M, Zettl UK. Polypharmacy in patients with multiple sclerosis: a gender-specific analysis. Biol Sex Differ. 2019;10(1):27. https://doi.org/10.1186/s13293-019-0243-9.CrossRefPubMedPubMedCentral

21.

Patti F, Penaherrera JN, Zieger L, Wicklein EM. Clinical characteristics of middle-aged and older patients with MS treated with interferon beta-1b: post-hoc analysis of a 2-year, prospective, international, observational study. BMC Neurol. 2021;21(1):324. https://doi.org/10.1186/s12883-021-02347-w.CrossRefPubMedPubMedCentral

22.

Zanghì A, D’Amico E, Lo Fermo S, Patti F. Exploring polypharmacy phenomenon in newly diagnosed relapsing-remitting multiple sclerosis: a cohort ambispective single-centre study. Ther Adv Chronic Dis. 2021;12:2040622320983121. https://doi.org/10.1177/2040622320983121.CrossRefPubMedPubMedCentral

23.

• Chertcoff A, Ng HS, Zhu F, Zhao Y, Tremlett H. Polypharmacy and multiple sclerosis: A population-based study. Mult Scler. 2023;29(1):107–18. https://doi.org/10.1177/13524585221122207. This study evaluated the prevalence and characteristics of polypharmacy in people with multiple sclerosis.CrossRefPubMed

24.

Frahm N, Hecker M, Zettl UK. Multi-drug use among patients with multiple sclerosis: A cross-sectional study of associations to clinicodemographic factors. Sci Rep. 2019;9(1):3743. https://doi.org/10.1038/s41598-019-40283-5.CrossRefPubMedPubMedCentral

25.

Marrie RA, Salter A, Tyry T, Fox RJ, Cutter GR. Health literacy association with health behaviors and health care utilization in multiple sclerosis: a cross-sectional study. Interact J Med Res. 2014;3(1):e3. https://doi.org/10.2196/ijmr.2993.CrossRefPubMedPubMedCentral

26.

•• Frahm N, Hecker M, Zettl UK. Polypharmacy among patients with multiple sclerosis: a qualitative systematic review. Expert Opin Drug Saf. 2020;19(2):139–45. https://doi.org/10.1080/14740338.2020.1720646. This review summarized early research and knowledge of polypharmacy in people with multiple sclerosis.CrossRefPubMed

27.

Frahm N, Hecker M, Langhorst SE, Mashhadiakbar P, Haker MC, Zettl UK. The risk of polypharmacy, comorbidities and drug-drug interactions in women of childbearing age with multiple sclerosis. Ther Adv Neurol Disord. 2020;13:1756286420969501. https://doi.org/10.1177/1756286420969501.CrossRefPubMedPubMedCentral

28.

•• Hartung DM, Johnston KA, McGregor JC, Bourdette DN. Characteristics of Prescription Drug Use Among Individuals With Multiple Sclerosis in the US Medicare Population. Int J MS Care. 2022;24(2):90–7. https://doi.org/10.7224/1537-2073.2021-062. This study described prescription drug use in people with multiple sclerosis in the US Medicare population.CrossRefPubMedPubMedCentral

29.

Thelen JM, Lynch SG, Bruce AS, Hancock LM, Bruce JM. Polypharmacy in multiple sclerosis: relationship with fatigue, perceived cognition, and objective cognitive performance. J Psychosom Res. 2014;76(5):400–4. https://doi.org/10.1016/j.jpsychores.2014.02.013.CrossRefPubMed

30.

Suárez MDMS, Roldán AM, Cuenca MRC, Morales AJ. Prevalence of PIMDINAC criteria and recommendations for therapeutic appropriateness in multiple sclerosis patients [Internet]. In Review; 2023 Feb [cited 2023 Apr 18]. Available from: https://www.researchsquare.com/article/rs-2609097/v1.

31.

Jelinek GA, Weiland TJ, Hadgkiss EJ, Marck CH, Pereira N, van der Meer DM. Medication use in a large international sample of people with multiple sclerosis: associations with quality of life, relapse rate and disability. Neurol Res. 2015;37(8):662–73. https://doi.org/10.1179/1743132815y.0000000036.CrossRefPubMedPubMedCentral

32.

•• Thelen J, Zvonarev V, Lam S, Burkhardt C, Lynch S, Bruce J. Polypharmacy in Multiple Sclerosis: Current Knowledge and Future Directions. Mo Med. 2021;118(3):239–45. This paper reviewed recent literature on polypharmacy in people with multiple sclerosis.PubMedPubMedCentral

33.

Evans C, Marrie RA, Zhu F, Leung S, Lu X, Kingwell E, et al. Adherence to disease-modifying therapies for multiple sclerosis and subsequent hospitalizations. Pharmacoepidemiol Drug Saf. 2017;26(6):702–11. https://doi.org/10.1002/pds.4207.CrossRefPubMed

34.

Cameron MH, Karstens L, Hoang P, Bourdette D, Lord S. Medications Are Associated with Falls in People with Multiple Sclerosis: A Prospective Cohort Study. Int J MS Care. 2015;17(5):207–14. https://doi.org/10.7224/1537-2073.2014-076.CrossRefPubMedPubMedCentral

35.

Debus JL, Bachmann P, Frahm N, Mashhadiakbar P, Langhorst SE, Streckenbach B, et al. Associated factors of potential drug-drug interactions and drug-food interactions in patients with multiple sclerosis. Ther Adv Chronic Dis. 2022;13:20406223221108390. https://doi.org/10.1177/20406223221108391.CrossRefPubMedPubMedCentral

36.

Yadav V, Shinto L, Bourdette D. Complementary and alternative medicine for the treatment of multiple sclerosis. Expert Rev Clin Immunol. 2010;6(3):381–95. https://doi.org/10.1586/eci.10.12.CrossRefPubMedPubMedCentral

37.

Hecker M, Frahm N, Bachmann P, Debus JL, Haker MC, Mashhadiakbar P, et al. Screening for severe drug-drug interactions in patients with multiple sclerosis: A comparison of three drug interaction databases. Front Pharmacol. 2022;13:946351. https://doi.org/10.3389/fphar.2022.946351.CrossRefPubMedPubMedCentral

38.

Beiske GA, Holmøy T, Beiske AG, Johannessen SI, Johannessen Landmark C. Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple Sclerosis. Mult Scler Int. 2015;2015:317859. https://doi.org/10.1155/2015/317859.CrossRefPubMedPubMedCentral

39.

Barbieri MA, Sorbara EE, Battaglia A, Cicala G, Rizzo V, Spina E, et al. Adverse Drug Reactions with Drugs Used in Multiple Sclerosis: An Analysis from the Italian Pharmacovigilance Database. Front Pharmacol. 2022;13:808370. https://doi.org/10.3389/fphar.2022.808370.CrossRefPubMedPubMedCentral

40.

Chertcoff A, Ng HS, Zhu F, Zhao Y, Kingwell E, Tremlett H. Alemtuzumab and prescription medication use in the MS population. Mult Scler Relat Disord. 2020;42:102086. https://doi.org/10.1016/j.msard.2020.102086.CrossRefPubMed

41.

Gotta M, Mayer CA, Huebner J. Use of complementary and alternative medicine in patients with multiple sclerosis in Germany. Complement Ther Med. 2018;36:113–7. https://doi.org/10.1016/j.ctim.2017.12.006.CrossRefPubMed

42.

Shariff EM, Al-Shammrani FJ, Nazish S, Zafar AS, Shahid RM, Khuda IE, et al. Is non-traditional therapy for multiple sclerosis overwhelming in Saudi Arabia. Neurosciences (Riyadh). 2019;24(3):192–8. https://doi.org/10.17712/nsj.2019.3.20180010.CrossRefPubMedPubMedCentral

43.

Wright S, Yadav V, Bever C Jr, Bowen J, Bowling A, Weinstock-Guttman B, et al. Summary of evidence-based guideline: complementary and alternative medicine in multiple sclerosis: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014;83(16):1484–6. https://doi.org/10.1212/01.wnl.0000455935.13606.91.CrossRefPubMed

44.

Rice J, Cameron M. Cannabinoids for Treatment of MS Symptoms: State of the Evidence. Curr Neurol Neurosci Rep. 2018;18(8):50. https://doi.org/10.1007/s11910-018-0859-x.CrossRefPubMed

45.

Oken BS, Flegal K, Zajdel D, Kishiyama SS, Lovera J, Bagert B, et al. Cognition and fatigue in multiple sclerosis: Potential effects of medications with central nervous system activity. J Rehabil Res Dev. 2006;43(1):83–90. https://doi.org/10.1682/jrrd.2004.11.0148.CrossRefPubMed

46.

Marrie RA, Fisk JD, Walld R, Bolton JM, Sareen J, Patten SB, et al. Use of Benzodiazepines and Z-Drugs in Multiple Sclerosis. Front Neurol. 2022;13:874724. https://doi.org/10.3389/fneur.2022.874724.CrossRefPubMedPubMedCentral

47.

Attarian H, Applebee G, Applebee A, Wang B, Clark M, McCormick B, et al. Effect of eszopiclone on sleep disturbances and daytime fatigue in multiple sclerosis patients. Int J MS Care. 2011;13(2):84–90. https://doi.org/10.7224/1537-2073-13.2.84.CrossRefPubMedPubMedCentral

48.

Kuehn BM. Growing Role of Gabapentin in Opioid-Related Overdoses Highlights Misuse Potential and Off-label Prescribing Practices. JAMA. 2022;328(13):1283–5. https://doi.org/10.1001/jama.2022.13659.CrossRefPubMed

49.

Cutter NC, Scott DD, Johnson JC, Whiteneck G. Gabapentin effect on spasticity in multiple sclerosis: a placebo-controlled, randomized trial. Arch Phys Med Rehabil. 2000;81(2):164–9. https://doi.org/10.1016/s0003-9993(00)90135-7.CrossRefPubMed

50.

Goodman CW, Brett AS. A Clinical Overview of Off-label Use of Gabapentinoid Drugs. JAMA Intern Med. 2019;179(5):695–701. https://doi.org/10.1001/jamainternmed.2019.0086.CrossRefPubMed

51.

Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022. MMWR Recomm Rep. 2022;71(3):1–95.CrossRefPubMedPubMedCentral

52.

Mattson CL, Chowdhury F, Gilson TP. Notes from the Field: Trends in Gabapentin Detection and Involvement in Drug Overdose Deaths - 23 States and the District of Columbia, 2019–2020. MMWR Morb Mortal Wkly Rep. 2022;71(19):664–6. https://doi.org/10.15585/mmwr.mm7119a3.CrossRefPubMedPubMedCentral

53.

Boustani M, Campbell N, Munger S, Maidment I, Fox C. Impact of anticholinergics on the aging brain: a review and practical application. Aging Health. 2008;4(3):311–20. https://doi.org/10.2217/1745509x.4.3.311.CrossRef

54.

Akkoc Y. Efficacy and safety of mirabegron for treatment of neurogenic detrusor overactivity in adults with spinal cord injury or multiple sclerosis: a systematic review. Spinal Cord. 2022;60(10):854–61. https://doi.org/10.1038/s41393-022-00853-3.CrossRefPubMed

55.

Comber L, Quinn G, McGuigan C, Galvin R, Coote S. Medication usage and falls in people with multiple sclerosis. Mult Scler. 2018;24(7):995–8. https://doi.org/10.1177/1352458517731912.CrossRefPubMed

56.

Cruce R, Vosoughi R, Freedman MS. Cognitive impact of anticholinergic medication in MS: Adding insult to injury? Mult Scler Relat Disord. 2012;1(4):156–61. https://doi.org/10.1016/j.msard.2012.05.002.CrossRefPubMed

57.

Morrow SA, Rosehart H, Sener A, Welk B. Anti-cholinergic medications for bladder dysfunction worsen cognition in persons with multiple sclerosis. J Neurol Sci. 2018;385:39–44. https://doi.org/10.1016/j.jns.2017.11.028.CrossRefPubMed

58.

Carrière I, Fourrier-Reglat A, Dartigues JF, Rouaud O, Pasquier F, Ritchie K, et al. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study. Arch Intern Med. 2009;169(14):1317–24. https://doi.org/10.1001/archinternmed.2009.229.CrossRefPubMedPubMedCentral

59.

Konishi K, Hori K, Uchida H, Watanabe K, Tominaga I, Kimura M, et al. Adverse effects of anticholinergic activity on cognitive functions in Alzheimer’s disease. Psychogeriatrics. 2010;10(1):34–8. https://doi.org/10.1111/j.1479-8301.2010.00310.x.CrossRefPubMed

60.

Pieper NT, Grossi CM, Chan WY, Loke YK, Savva GM, Haroulis C, et al. Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline: a meta-analysis. Age Ageing. 2020;49(6):939–47. https://doi.org/10.1093/ageing/afaa090.CrossRefPubMedPubMedCentral

61.

Seo SW, Suh MK, Chin J, Na DL. Mental confusion associated with scopolamine patch in elderly with mild cognitive impairment (MCI). Arch Gerontol Geriatr. 2009;49(2):204–7. https://doi.org/10.1016/j.archger.2008.07.011.CrossRefPubMed

62.

Taylor-Rowan M, Kraia O, Kolliopoulou C, Noel-Storr AH, Alharthi AA, Cross AJ, Stewart C, Myint PK, Mccleery J, Quinn TJ. Anticholinergic burden for prediction of cognitive decline or neuropsychiatric symptoms in older adults with mild cognitive impairment or dementia. Cochrane Database Syst Rev. 2022. https://doi.org/10.1002/14651858.cd015196.CrossRefPubMedPubMedCentral

63.

Salahudeen MS, Duffull SB, Nishtala PS. Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: a systematic review. BMC Geriatr. 2015;15:31. https://doi.org/10.1186/s12877-015-0029-9.CrossRefPubMedPubMedCentral

64.

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(5):827–34. https://doi.org/10.1001/jamainternmed.2015.0324.CrossRefPubMed

65.

Lam K, Rochon PA, Steinman MA. Often Off-label: Questionable Gabapentinoid Use Noted at Hospital Admission Warrants Deprescribing. J Hosp Med. 2019;14(9):579–80. https://doi.org/10.12788/jhm.3245.CrossRefPubMedPubMedCentral

66.

Kua CH, Mak VSL, Huey Lee SW. Health Outcomes of Deprescribing Interventions Among Older Residents in Nursing Homes: A Systematic Review and Meta-analysis. J Am Med Dir Assoc. 2019;20(3):362-72.e11. https://doi.org/10.1016/j.jamda.2018.10.026.CrossRefPubMed

67.

Lee JY, Farrell B, Holbrook AM. Deprescribing benzodiazepine receptor agonists taken for insomnia: a review and key messages from practice guidelines. Pol Arch Intern Med. 2019;129(1):43–9. https://doi.org/10.20452/pamw.4391.CrossRefPubMed

68.

Bjerre LM, Farrell B, Hogel M, Graham L, Lemay G, McCarthy L, et al. Deprescribing antipsychotics for behavioural and psychological symptoms of dementia and insomnia: Evidence-based clinical practice guideline. Can Fam Phys. 2018;64(1):17–27.

69.

Pottie K, Thompson W, Davies S, Grenier J, Sadowski CA, Welch V, et al. Deprescribing benzodiazepine receptor agonists: Evidence-based clinical practice guideline. Can Fam Phys. 2018;64(5):339–51.

70.

Reeve E, Farrell B, Thompson W, Herrmann N, Sketris I, Magin PJ, et al. Deprescribing cholinesterase inhibitors and memantine in dementia: guideline summary. Med J Aust. 2019;210(4):174–9. https://doi.org/10.5694/mja2.50015.CrossRefPubMed

Title: Polypharmacy in Multiple Sclerosis: Prevalence, Risks, and Mitigation Strategies
Authors: W. Daniel Chapman
Megan C. Herink
Michelle H. Cameron
Dennis Bourdette
Publication date: 31-07-2023
Publisher: Springer US
Keyword: Multiple Sclerosis
Published in: Current Neurology and Neuroscience Reports / Issue 9/2023
Print ISSN: 1528-4042
Electronic ISSN: 1534-6293
DOI: https://doi.org/10.1007/s11910-023-01289-9

2024 ASCO Annual Meeting

Springer Medicine

Polypharmacy in Multiple Sclerosis: Prevalence, Risks, and Mitigation Strategies

Abstract

Purpose of Review

Recent Findings

Summary

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

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