Changes in prescribed medicines in older patients with multimorbidity and polypharmacy in general practice

Fiona von Buedingen, Marc S Hammer, Andreas D Meid, Walter E Müller, Ferdinand M Gerlach, Christiane Muth, Fiona von Buedingen, Marc S Hammer, Andreas D Meid, Walter E Müller, Ferdinand M Gerlach, Christiane Muth

Abstract

Background: Treatment complexity rises in line with the number of drugs, single doses, and administration methods, thereby threatening patient adherence. Patients with multimorbidity often need flexible, individualised treatment regimens, but alterations during the course of treatment may further increase complexity. The objective of our study was to explore medication changes in older patients with multimorbidity and polypharmacy in general practice.

Methods: We retrospectively analysed data from the cluster-randomised PRIMUM trial (PRIoritisation of MUltimedication in Multimorbidity) conducted in 72 general practices. We developed an algorithm for active pharmaceutical ingredients (API), strength, dosage, and administration method to assess changes in physician-reported medication data during two intervals (baseline to six-months: ∆1; six- to nine-months: ∆2), analysed them descriptively at prescription and patient levels, and checked for intervention effects.

Results: Of 502 patients (median age 72 years, 52% female), 464 completed the study. Changes occurred in 98.6% of patients (changes were 19% more likely in the intervention group): API changes during ∆1 and ∆2 occurred in 414 (82.5%) and 338 (67.3%) of patients, dosage alterations in 372 (74.1%) and 296 (59.2%), and changes in API strength in 158 (31.5%) and 138 (27.5%) respectively. Administration method changed in 79 (16%) of patients in both ∆1 and ∆2. Simvastatin, metformin and aspirin were most frequently subject to alterations.

Conclusion: Medication regimens in older patients with multimorbidity and polypharmacy changed frequently. These are mostly due to discontinuations and dosage alterations, followed by additions and restarts. These findings cast doubt on the effectiveness of cross-sectional assessments of medication and support longitudinal assessments where possible.

Trial registration: 1. Prospective registration: Trial registration number: NCT01171339 ; Name of registry: ClinicalTrials.gov; Date of registration: July 27, 2010; Date of enrolment of the first participant to the trial: August 12, 2010. 2. Peer reviewed trial registration: Trial registration number: ISRCTN99526053 ; Name of registry: Controlled Trials; Date of registration: August 31, 2010; Date of enrolment of the first participant to the trial: August 12, 2010.

Keywords: General practice; Medication changes; Multimorbidity; Multiple chronic conditions; Older adults; Polypharmacy.

Conflict of interest statement

Consent for publication

Not applicable.

Competing interests

FMG and CM report grants from German Federal Ministry of Education and Research, BMBF, grant no. 01GK0702, during the conduct of the PRIMUM study. ADM report grants from German Federal Ministry of Education and Research, BMBF, grant no. 01GY1320B, during the conduct of the PRIMUM study. FvB, MSH and WEM declared no conflicts of interest.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Medication Changes at Prescribing Level. API: active pharmaceutical ingredient. 1ATC-Code 5 digits. ATC: anatomical therapeutic chemical classification system. Interval ∆1: baseline to six-month follow-up; interval ∆2: six- to nine-month follow-ups
Fig. 2
Fig. 2
Medication Changes at Patient Level. Interval ∆1: baseline to six-month follow-up; interval ∆2: six- to nine-month follow-ups

References

    1. Salisbury C, Johnson L, Purdy S, Valderas JM, Montgomery AA. Epidemiology and impact of multimorbidity in primary care: a retrospective cohort study. Br J Gen Pract. 2011;61(582):e12–e21. doi: 10.3399/bjgp11X548929.
    1. van den Akker M, Buntinx F, Knottnerus J. Comorbidity or multimorbidity: what's in a name. A review of literature. Eur J Gen Pract. 1996;2:65–70. doi: 10.3109/13814789609162146.
    1. Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017;17(1):230. doi: 10.1186/s12877-017-0621-2.
    1. Campbell SE, Seymour DG, Primrose WR, Lynch JE, Dunstan E, Espallargues M, Lamura G, Lawson P, Philp I, Mestheneos E, et al. A multi-Centre European study of factors affecting the discharge destination of older people admitted to hospital: analysis of in-hospital data from the ACMEplus project. Age Ageing. 2005;34(5):467–475. doi: 10.1093/ageing/afi141.
    1. Davies EC, Green CF, Taylor S, Williamson PR, Mottram DR, Pirmohamed M. Adverse drug reactions in hospital in-patients: a prospective analysis of 3695 patient-episodes. PLoS One. 2009;4(2):e4439. doi: 10.1371/journal.pone.0004439.
    1. Deandrea S, Lucenteforte E, Bravi F, Foschi R, La VC, Negri E. Risk factors for falls in community-dwelling older people: a systematic review and meta-analysis. Epidemiology. 2010;21(5):658–668. doi: 10.1097/EDE.0b013e3181e89905.
    1. Grimmsmann T, Himmel W. Polypharmacy in primary care practices: an analysis using a large health insurance database. Pharmacoepidemiol Drug Saf. 2009;18(12):1206–1213. doi: 10.1002/pds.1841.
    1. Hakkarainen KM, Gyllensten H, Jonsson AK, Andersson SK, Petzold M, Hagg S. Prevalence, nature and potential preventability of adverse drug events - a population-based medical record study of 4970 adults. Br J Clin Pharmacol. 2014;78(1):170–183. doi: 10.1111/bcp.12314.
    1. Meid AD, Quinzler R, Groll A, Wild B, Saum KU, Schottker B, Heider D, Konig HH, Brenner H, Haefeli WE. Longitudinal evaluation of medication underuse in older outpatients and its association with quality of life. Eur J Clin Pharmacol. 2016;72(7):877–885. doi: 10.1007/s00228-016-2047-8.
    1. Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, Farrar K, Park BK, Breckenridge AM. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ. 2004;329(7456):15–19. doi: 10.1136/bmj.329.7456.15.
    1. Thomson LA, Winterstein AG, Sondergaard B, Haugbolle LS, Melander A. Systematic review of the incidence and characteristics of preventable adverse drug events in ambulatory care. Ann Pharmacother. 2007;41(9):1411–1426. doi: 10.1345/aph.1H658.
    1. Viktil KK, Blix HS, Moger TA, Reikvam A. Polypharmacy as commonly defined is an indicator of limited value in the assessment of drug-related problems. Br J Clin Pharmacol. 2007;63(2):187–195. doi: 10.1111/j.1365-2125.2006.02744.x.
    1. Boyd CM, Darer J, Boult C, Fried LP, Boult L, Wu AW. Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance. JAMA. 2005;294(6):716–724. doi: 10.1001/jama.294.6.716.
    1. Muir AJ, Sanders LL, Wilkinson WE, Schmader K. Reducing medication regimen complexity: a controlled trial. J Gen Intern Med. 2001;16(2):77–82. doi: 10.1046/j.1525-1497.2001.016002077.x.
    1. Rambhade S, Chakarborty A, Shrivastava A, Patil UK, Rambhade A. A survey on polypharmacy and use of inappropriate medications. Toxicol Int. 2012;19(1):68–73. doi: 10.4103/0971-6580.94506.
    1. Horne R, Weinman J, Barber N, Elliott R, Morgan M, Cribb A, I K: Concordance, adherence and compliance in medicine taking. National Coordinating Centre for the Service Delivery and Organisation (NCCSDO) 2005. URL: ; Accessed: 08/07/2018.
    1. George J, Phun YT, Bailey MJ, Kong DC, Stewart K. Development and validation of the medication regimen complexity index. Ann Pharmacother. 2004;38(9):1369–1376. doi: 10.1345/aph.1D479.
    1. Stone VE, Hogan JW, Schuman P, Rompalo AM, Howard AA, Korkontzelou C, Smith DK. Antiretroviral regimen complexity, self-reported adherence, and HIV patients' understanding of their regimens: survey of women in the her study. J Acquir Immune Defic Syndr. 2001;28(2):124–131. doi: 10.1097/00126334-200110010-00003.
    1. Haslbeck JW, Schaeffer D. Routines in medication management: the perspective of people with chronic conditions. Chronic Illn. 2009;5(3):184–196. doi: 10.1177/1742395309339873.
    1. Lam KD, Miao Y, Steinman MA. Cumulative changes in the use of long-term medications: a measure of prescribing complexity. JAMA Intern Med. 2013;173(16):1546–1547. doi: 10.1001/jamainternmed.2013.7060.
    1. Muth C, van den Akker M, Blom JW, Mallen CD, Rochon J, Schellevis FG, Becker A, Beyer M, Gensichen J, Kirchner H, et al. The Ariadne principles: how to handle multimorbidity in primary care consultations. BMC Med. 2014;12:223. doi: 10.1186/s12916-014-0223-1.
    1. NICE: Multimorbidity: clinical assessment and management. Multimorbidity: assessment, prioritisation and management of care for people with commonly occurring multimorbidity. NICE guideline NG56. National Institute for Health and Care Excellence. 2016. URL: ; Accessed: 08/07/2018.
    1. Spinewine A, Schmader KE, Barber N, Hughes C, Lapane KL, Swine C, Hanlon JT. Appropriate prescribing in elderly people: how well can it be measured and optimised? Lancet. 2007;370(9582):173–184. doi: 10.1016/S0140-6736(07)61091-5.
    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;56(10):1946–1952. doi: 10.1111/j.1532-5415.2008.01916.x.
    1. Sinnott C, Hugh SM, Boyce MB, Bradley CP. What to give the patient who has everything? A qualitative study of prescribing for multimorbidity in primary care. Br J Gen Pract. 2015;65(632):e184–e191. doi: 10.3399/bjgp15X684001.
    1. 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(12):e006544. doi: 10.1136/bmjopen-2014-006544.
    1. Sinnott C, McHugh S, Browne J, Bradley C. GPs' perspectives on the management of patients with multimorbidity: systematic review and synthesis of qualitative research. BMJ Open. 2013;3(9):e003610. doi: 10.1136/bmjopen-2013-003610.
    1. Bergert FW, Braun M, Ehrenthal K, Fessler J, Gross J, Huttner U, Kluthe B, Liesenfeld A, Seffrin J, Vetter G, et al. Recommendations for treating adult and geriatric patients on multimedication. Int J Clin Pharmacol Ther. 2014;52(Suppl 1):1–64. doi: 10.5414/CPP52S001.
    1. Grimmsmann T, Schwabe U, Himmel W. The influence of hospitalisation on drug prescription in primary care--a large-scale follow-up study. Eur J Clin Pharmacol. 2007;63(8):783–790. doi: 10.1007/s00228-007-0325-1.
    1. Larsen MD, Rosholm JU, Hallas J. The influence of comprehensive geriatric assessment on drug therapy in elderly patients. Eur J Clin Pharmacol. 2014;70(2):233–239. doi: 10.1007/s00228-013-1601-x.
    1. Wilson A, Childs S. The relationship between consultation length, process and outcomes in general practice: a systematic review. Br J Gen Pract. 2002;52(485):1012–1020.
    1. Muth C, Uhlmann L, Haefeli WE, Rochon J, van den AM PR, Guthlin C, Beyer M, Oswald F, Valderas JM, et al. effectiveness of a complex intervention on Prioritising multimedication in multimorbidity (PRIMUM) in primary care: results of a pragmatic cluster randomised controlled trial. BMJ Open. 2018;8(2):e017740.
    1. Muth C, Harder S, Uhlmann L, Rochon J, Fullerton B, Guthlin C, Erler A, Beyer M, van den AM PR, et al. pilot study to test the feasibility of a trial design and complex intervention on PRIoritising MUltimedication in multimorbidity in general practices (PRIMUMpilot) BMJ Open. 2016;6(7):e011613. doi: 10.1136/bmjopen-2016-011613.
    1. Bosley S, Dale J. Healthcare assistants in general practice: practical and conceptual issues of skill-mix change. Br J Gen Pract. 2008;58(547):118–124. doi: 10.3399/bjgp08X277032.
    1. Gensichen J, von Korff M, Peitz M, Muth C, Beyer M, Guthlin C, Torge M, Petersen JJ, Rosemann T, Konig J, et al. Case management for depression by health care assistants in small primary care practices: a cluster randomized trial. Ann Intern Med. 2009;151(6):369–378. doi: 10.7326/0003-4819-151-6-200909150-00001.
    1. Peters-Klimm F, Muller-Tasch T, Schellberg D, Gensichen J, Muth C, Herzog W, Szecsenyi J. Rationale, design and conduct of a randomised controlled trial evaluating a primary care-based complex intervention to improve the quality of life of heart failure patients: HICMan (Heidelberg integrated case management) BMC Cardiovasc Disord. 2007;7:25. doi: 10.1186/1471-2261-7-25.
    1. Rosemann T, Joos S, Laux G, Gensichen J, Szecsenyi J. Case management of arthritis patients in primary care: a cluster-randomized controlled trial. Arthritis Rheum. 2007;57(8):1390–1397. doi: 10.1002/art.23080.
    1. Rosemann T, Korner T, Wensing M, Gensichen J, Muth C, Joos S, Szecsenyi J. Rationale, design and conduct of a comprehensive evaluation of a primary care based intervention to improve the quality of life of osteoarthritis patients. The PraxArt-project: a cluster randomized controlled trial [ISRCTN87252339] BMC Public Health. 2005;5:77. doi: 10.1186/1471-2458-5-77.
    1. Gensichen J, Muth C, Butzlaff M, Rosemann T, Raspe H, de Cornejo GM, Beyer M, Harter M, Muller UA, Angermann CE, et al. the future is chronic: German primary care and the chronic care model--the comprehensive principles in the proactive treatment of the chronically ill. Z Arztl Fortbild Qualitatssich. 2006;100(5):365–374.
    1. Beyer M, Otterbach I, Erler A, Muth C, Gensichen J, Gerlach FM. Multimorbidität in der Allgemeinpraxis. Teil 1: Pragmatische definition, Epidemiologie und Versorgungsprämissen. [multimorbidity in general practice. Part I: a pragmatic definition, epidemiology, prerequisites of care.] Z Allgemeinmed. 2007;83(8):310–315. doi: 10.1055/s-2007-985383.
    1. Hudon C, Fortin M, Soubhi H. Abbreviated guidelines for scoring the cumulative illness rating scale (CIRS) in family practice. J Clin Epidemiol. 2007;60(2):212. doi: 10.1016/j.jclinepi.2005.12.021.
    1. Linn BS, Linn MW, Gurel L. Cumulative illness rating scale. J Am Geriatr Soc. 1968;16(5):622–626. doi: 10.1111/j.1532-5415.1968.tb02103.x.
    1. Fournier DA, Skaug HJ, Ancheta J, Ianelli J, Magnusson A, Maunder MN, Nielsen A, Sibert J. AD model builder: using automatic differentiation for statistical inference of highly parameterized complex nonlinear models. Optim Methods Softw. 2012;27(2):233–249. doi: 10.1080/10556788.2011.597854.
    1. Aly SS, Zhao J, Li B, Jiang J. Reliability of environmental sampling culture results using the negative binomial intraclass correlation coefficient. Springerplus. 2014;3:40. doi: 10.1186/2193-1801-3-40.
    1. Cadogan CA, Ryan C, Hughes CM. Appropriate polypharmacy and medicine safety: when many is not too many. Drug Saf. 2016;39(2):109–116. doi: 10.1007/s40264-015-0378-5.
    1. Cooper JA, Cadogan CA, Patterson SM, Kerse N, Bradley MC, Ryan C, Hughes CM. Interventions to improve the appropriate use of polypharmacy in older people: a Cochrane systematic review. BMJ Open. 2015;5(12):e009235. doi: 10.1136/bmjopen-2015-009235.
    1. Meid AD, Haefeli WE. Age-dependent impact of medication underuse and strategies for improvement. Gerontology. 2016;62(5):491–499. doi: 10.1159/000443477.
    1. Rossello X, Pocock SJ, Julian DG. Long-term use of cardiovascular drugs: challenges for research and for patient care. J Am Coll Cardiol. 2015;66(11):1273–1285. doi: 10.1016/j.jacc.2015.07.018.
    1. Backes JM, Ruisinger JF, Gibson CA, Moriarty PM. Statin-associated muscle symptoms-managing the highly intolerant. J Clin Lipidol. 2017;11(1):24–33. doi: 10.1016/j.jacl.2017.01.006.
    1. Stulc T, Ceska R, Gotto AM., Jr Statin intolerance: the Clinician's perspective. Curr Atheroscler Rep. 2015;17(12):69. doi: 10.1007/s11883-015-0552-3.
    1. 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(4):121–124. doi: 10.1136/eb-2012-100930.
    1. Furtado RH, Giugliano RP, Strunz CM, Filho CC, Ramires JA, Filho RK, Neto PA, Pereira AC, Rocha TR, Freire BT, et al. Drug interaction between Clopidogrel and ranitidine or omeprazole in stable coronary artery disease: a double-blind, double dummy, Randomized Study. Am J Cardiovasc Drugs. 2016;16(4):275–284. doi: 10.1007/s40256-016-0172-5.
    1. 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(18):1648–1654. doi: 10.1001/archinternmed.2010.355.
    1. van der Velde N, Stricker BH, Pols HA, van der Cammen TJ. Risk of falls after withdrawal of fall-risk-increasing drugs: a prospective cohort study. Br J Clin Pharmacol. 2007;63(2):232–237. doi: 10.1111/j.1365-2125.2006.02736.x.
    1. Potter K, Flicker L, Page A, Etherton-Beer C. Deprescribing in frail older people: a randomised controlled trial. PLoS One. 2016;11(3):e0149984. doi: 10.1371/journal.pone.0149984.
    1. 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(6):430–434.
    1. Hanlon JT, Schmader KE, Samsa GP, Weinberger M, Uttech KM, Lewis IK, Cohen HJ, Feussner JR. A method for assessing drug therapy appropriateness. J Clin Epidemiol. 1992;45(10):1045–1051. doi: 10.1016/0895-4356(92)90144-C.
    1. Hanlon JT, Schmader KE. The medication appropriateness index at 20: where it started, where it has been, and where it may be going. Drugs Aging. 2013;30(11):893–900. doi: 10.1007/s40266-013-0118-4.
    1. Howard RL, Avery AJ, Slavenburg S, Royal S, Pipe G, Lucassen P, Pirmohamed M. Which drugs cause preventable admissions to hospital? A systematic review. Br J Clin Pharmacol. 2007;63(2):136–147. doi: 10.1111/j.1365-2125.2006.02698.x.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅