The rising tide of polypharmacy and drug-drug interactions: population database analysis 1995-2010

Bruce Guthrie, Boikanyo Makubate, Virginia Hernandez-Santiago, Tobias Dreischulte, Bruce Guthrie, Boikanyo Makubate, Virginia Hernandez-Santiago, Tobias Dreischulte

Abstract

Background: The escalating use of prescribed drugs has increasingly raised concerns about polypharmacy. This study aims to examine changes in rates of polypharmacy and potentially serious drug-drug interactions in a stable geographical population between 1995 and 2010.

Methods: This is a repeated cross-sectional analysis of community-dispensed prescribing data for all 310,000 adults resident in the Tayside region of Scotland in 1995 and 2010. The number of drug classes dispensed and the number of potentially serious drug-drug interactions (DDIs) in the previous 84 days were calculated, and age-sex standardised rates in 1995 and 2010 compared. Patient characteristics associated with receipt of ≥ 10 drugs and with the presence of one or more DDIs were examined using multilevel logistic regression to account for clustering of patients within primary care practices.

Results: Between 1995 and 2010, the proportion of adults dispensed ≥ 5 drugs doubled to 20.8%, and the proportion dispensed ≥ 10 tripled to 5.8%. Receipt of ≥ 10 drugs was strongly associated with increasing age (20-29 years, 0.3%; ≥ 80 years, 24.0%; adjusted OR, 118.3; 95% CI, 99.5-140.7) but was also independently more common in people living in more deprived areas (adjusted OR most vs. least deprived quintile, 2.36; 95% CI, 2.22-2.51), and in people resident in a care home (adjusted OR, 2.88; 95% CI, 2.65-3.13). The proportion with potentially serious drug-drug interactions more than doubled to 13% of adults in 2010, and the number of drugs dispensed was the characteristic most strongly associated with this (10.9% if dispensed 2-4 drugs vs. 80.8% if dispensed ≥ 15 drugs; adjusted OR, 26.8; 95% CI 24.5-29.3).

Conclusions: Drug regimens are increasingly complex and potentially harmful, and people with polypharmacy need regular review and prescribing optimisation. Research is needed to better understand the impact of multiple interacting drugs as used in real-world practice and to evaluate the effect of medicine optimisation interventions on quality of life and mortality.

Figures

Figure 1
Figure 1
Number of drug classes dispensed in the 84-day period in 1995 and 2010 by age of patient.
Figure 2
Figure 2
Number of potentially serious drug-drug interactions in the 84-day period in 1995 and 2010 by age of patients.

References

    1. Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18,820 patients. BMJ. 2004;329:15–9. doi: 10.1136/bmj.329.7456.15.
    1. Howard R, Avery A, Slavenburg S, Royal S, Pipe G, Lucassen P, et al. Which drugs cause preventable admissions to hospital? A systematic review. Br J Clin Pharmacol. 2007;63:136–47. doi: 10.1111/j.1365-2125.2006.02698.x.
    1. Burgess C, Holman C, Satti A. Adverse drug reactions in older Australians, 1981–2002. Med J Aust. 2005;182:267–70.
    1. Bourgeois FT, Shannon MW, Valim C, Mandl KD. Adverse drug events in the outpatient setting: an 11-year national analysis. Pharmacoepidemiol Drug Saf. 2010;19:901–10. doi: 10.1002/pds.1984.
    1. Barnett K, Mercer SW, Norbury M, Watt G, Wyke S, Guthrie B. Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet. 2012;380:37–43. doi: 10.1016/S0140-6736(12)60240-2.
    1. Shah BM, Hajjar ER. Polypharmacy, adverse drug reactions, and geriatric syndromes. Clin Geriatr Med. 2012;28:173–86. doi: 10.1016/j.cger.2012.01.002.
    1. Gandhi TK, Weingart SN, Borus J, Seger AC, Peterson J, Burdick E, et al. Adverse drug events in ambulatory care. N Engl J Med. 2003;348:1556–64. doi: 10.1056/NEJMsa020703.
    1. Johnell K, Klarin I. The relationship between number of drugs and potential drug-drug interactions in the elderly: a study of over 600,000 elderly patients from the Swedish prescribed drug register. Drug Saf. 2007;30:911–8. doi: 10.2165/00002018-200730100-00009.
    1. Haider S, Johnell K, Thorslund M, Fastbom J. Trends in polypharmacy and potential drug-drug interactions across educational groups in elderly patients in Sweden for the period 1992–2002. Int J Clin Pharmacol Ther. 2007;45:643–53. doi: 10.5414/CPP45643.
    1. Aronson J. Polypharmacy, appropriate and inappropriate. Br J Gen Pract. 2006;56:484–5.
    1. Steinman MA, Hanlon JT. Managing medications in clinically complex elders. JAMA. 2010;304:1592–601. doi: 10.1001/jama.2010.1482.
    1. Van Spall HGC, Toren A, Kiss A, Fowler RA. Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review. JAMA. 2007;297:1233–40. doi: 10.1001/jama.297.11.1233.
    1. Masoudi FA, Havranek EP, Wolfe P, Gross CP, Rathore SS, Steiner JF, et al. Most hospitalized older persons do not meet the enrollment criteria for clinical trials in heart failure. Am Heart J. 2003;146:250–7. doi: 10.1016/S0002-8703(03)00189-3.
    1. Travers J, Marsh S, Caldwell B, Williams M, Aldington S, Weatherall M, et al. External validity of randomized controlled trials in COPD. Respir Med. 2007;101:1313–20. doi: 10.1016/j.rmed.2006.10.011.
    1. Saunders C, Byrne CD, Guthrie B, Lindsay RS, McKnight JA, Philip S, et al. External validity of randomized controlled trials of glycaemic control and vascular disease: how representative are participants? Diabet Med. 2013;30:300–8. doi: 10.1111/dme.12047.
    1. Hughes L, McMurdo MET, Guthrie B. Guidelines for people not for diseases: the challenges of applying UK clinical guidelines to people with multimorbidity. Age Ageing. 2013;42:62–9. doi: 10.1093/ageing/afs100.
    1. Guthrie B, Payne K, Alderson P, McMurdo MET, Mercer SW. Adapting clinical guidelines to take account of multimorbidity. BMJ. 2012;345:e6341. doi: 10.1136/bmj.e6341.
    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. JAMA. 2005;294:716–24. doi: 10.1001/jama.294.6.716.
    1. Nobili A, Pasina L, Tettamanti M, Lucca U, Riva E, Marzona I, et al. Potentially severe drug interactions in elderly outpatients: results of an observational study of an administrative prescription database. J Clin Pharm Ther. 2009;34:377–86. doi: 10.1111/j.1365-2710.2009.01021.x.
    1. Obreli Neto PR, Nobili A, Marusic S, Pilger D, Guidoni CM, Baldoni Ade O, et al. Prevalence and predictors of potential drug-drug interactions in the elderly: a cross-sectional study in the Brazilian primary public health system. J Pharm Pharm Sci. 2011;15:344–54.
    1. Lin C-F, Wang C-Y, Bai C-H. Polypharmacy, aging and potential drug-drug interactions in outpatients in Taiwan: a retrospective computerized screening study. Drugs Aging. 2011;28:219–25. doi: 10.2165/11586870-000000000-00000.
    1. Guthrie B, McCowan C, Davey P, Simpson CR, Dreischulte T, Barnett K. High risk prescribing in primary care patients particularly vulnerable to adverse drug events: cross sectional population database analysis in Scottish general practice. BMJ. 2011;342:d3514. doi: 10.1136/bmj.d3514.
    1. Office of the Chief Statistician . Scottish Index of Multiple Deprivation 2004 Summary Technical Report. Edinburgh: Scottish Executive; 2004.
    1. Fincke B, Snyder K, Cantillon C, Gaehde S, Standring P, Fiore L, et al. Three complementary definitions of polypharmacy: methods, application and comparison of findings in a large prescription database. Pharmacoepidemiol Drug Saf. 2005;14:121–8. doi: 10.1002/pds.966.
    1. British Medical Association, Royal Pharmaceutical Society . British National Formulary 59 (March 2010) London: BMJ Group and Pharmaceutical Press, London; 2010.
    1. Franchi C, Tettamanti M, Pasina L, Djignefa C, Fortino I, Bortolotti A, et al. Changes in drug prescribing to Italian community-dwelling elderly people: the EPIFARM–Elderly Project 2000–2010. Eur J Clin Pharmacol. 2014;70:437–43. doi: 10.1007/s00228-013-1621-6.
    1. MHRA Simvastatin: updated advice on drug interactions – updated contraindications. Drug Safety Update. 2012;6:S1.
    1. Patterson S, Hughes C, Kerse N, Caldwell C, Bradley M. Interventions to improve the appropriate use of polypharmacy for older people. Cochrane Database Syst Rev. 2012;5:CD008165.

Source: PubMed

3
Suscribir