Search tips
Search criteria 


Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Arch Pediatr Adolesc Med. Author manuscript; available in PMC 2013 January 1.
Published in final edited form as:
PMCID: PMC3248612

Pediatric Polypharmacy

Time to Lock the Medicine Cabinet?
Nancy E. Morden, MD, MPH and David Goodman, MD, MS

The use of therapeutic agents represents a trade-off between the benefits of symptom relief or disease modification that increase quality or length of life and the risk of short- and long-term adverse effects. While evidence suggests that complex medication combinations greatly increase the odds of incurring an adverse drug event,1-3 US Food and Drug Administration approval generally only requires testing of agents in isolation. As a consequence, we often do not know the net health outcomes associated with diverse and intense medication combinations. This uncertainty is magnified in the care of children for whom efficacy and safety studies are often lacking. Despite this therapeutic uncertainty, pediatric drug use is growing.4 A study in this issue of the Archives5 provides a critical examination of the drug exposure of pediatric inpatients. Polypharmacy is the norm for hospitalized infants and children. Should we be concerned?

See related article

Using 2 large detailed inpatient administrative data sets to quantify drug exposure among pediatric patients hospitalized in the United States, Feudtner and colleagues5 found a relatively high level of medication use. Median first-day exposure ranged from 3 to 5 unique product types. The median exposure on subsequent days ranged from 3 to 9 products. In fully adjusted models, hospital type (children’s or general) was not associated with the number of drugs used; overall exposure generally increased with patient age and with additional inpatient days. For 3 highlighted, common Diagnosis Related Groups (DRGs) (asthma, appendectomy, and seizure), cumulative medication exposure varied substantially across hospitals.

We share the authors’ unease with the level of polypharmacy in pediatric inpatient settings, but our biggest concern is the lack of information that would tell us if these prescribing patterns are problematic for patients. Inpatient pediatric care is complex, and it is not clear which medications and medication combinations are best for a hospitalized child. Certainly, relief of symptoms should be a priority. While medications aimed at alleviating symptoms can be overused, patients should not suffer in the name of parsimonious prescribing or unfounded fear for adverse effects. In particular, the tragic undertreatment of pain in children has been extensively documented.6,7 In addition, the use of anesthetics and sedatives may not be optional when surgery, procedures, or advanced imaging are required. After these general categories of drugs (symptom relief, sedatives, and anesthetics) children’s next most common exposures, as detailed in Table 2 of the article by Feudtner et al,5 are to antimicrobial and respiratory agents, broad categories in which appropriateness of some prescribing patterns is doubtful.8-10 Are pediatric patients receiving too much or too little?

The variation in DRG-specific drug exposures seen across hospitals suggests a lack of consensus among pediatric clinicians about medication prescribing for children. Unnecessary and potentially hazardous drug exposure likely occurs in some facilities, while in other hospitals, pediatric patients may be undertreated. Studying the variation in further detail will help to identify concerning patterns of prescribing and guide further research and clinical care improvement.

In an effort to advance safe and effective inpatient pharmacotherapy for children, an important next step is to use administrative data (eg, medical claims) to determine the common medications that represent marginal exposure in hospitals with high drug use and the medications most commonly “lacking” in low-use hospitals. These large data sets could also be used to measure outcomes associated with distinct exposure patterns. Observational studies such as these could add valuable information to randomized clinical trials and improve our understanding of the health impact of pediatric polypharmacy. Better use of medications should improve outcomes, reduce adverse effects, and save money.

Surveillance and research on the effects of pediatric polypharmacy should be prioritized and funded in proportion to the prevalence and likely patient impact of this issue. Such research should be funded by noncommercial sources. While pediatric polypharmacy is likely most common in the inpatient setting where acute illness or procedures drive medication use, outpatient polypharmacy is increasingly prevalent in children and also deserves attention.4 In nonhospitalized children, adverse effects related to short-term overlapping drug use similar to that in the inpatient setting, undoubtedly occur, but long-term effects of cumulative exposure may be equally important. Therapy with medications started in childhood for management of chronic conditions often continues for decades—well beyond the duration of any drug approval trials and thus well outside our understanding of potential drug effects.11,12 As we advance the research agenda of pediatric polypharmacy, it is important to consider this broad trend and to move forward with studies on the effects of long-term polypharmacy in children. Outcomes studies will depend on high-quality administrative data. It is sobering to realize that the availability and completeness of medical claims data for children still falls far short of Medicare data used to study the elderly population. Feudtner et al5 and other investigators could accelerate improvement in the care of children if permitted access to data that include all medical care events (eg, discharges, outpatient visits, pharmacy claims) for a large pediatric population whose care can be linked over time and to specific providers.

Clinicians, policy makers, researchers, and patient advocates should collaborate on efforts aimed at promoting the development of evidence to inform pediatric pharmacotherapy. Moving toward an understanding of the balance of risks and benefits will require better data, a sustained research program, and a commitment to translating new knowledge into better practice.


Funding/Support: Dr Goodman currently receives research funding through grants and contracts from the Robert Wood Johnson Foundation; Health Resources and Services Administration; Department of Health and Human Services, Office of the Assistant Secretary of Planning and Evaluation; The National Institute on Aging (grant PO1 AG19783); National Cancer Institute; and the Well-point Foundation.


Financial Disclosure: In the last 36 months, Dr Goodman has received speaking fees from the Texas Medical Association (2008); Health Action Council, Cincinnati (2008); Richard Stockton College of New Jersey (2008); Iowa Health Business Alliance (2008); Alliance for Academic Internal Medicine (2008); American Medical Association (2008); Connecticut Children’s Hospital (2008); Mt Sinai Hospital, New York (2009); World Congress (2009 and 2010); Rutgers University (2009); Baystate Medical Center (2009); Brigham and Women’s Hospital (2009); ESRI Inc (2009); Illinois Hospital Association (2008, 2009, and 2010); National Hospice Workgroup (2009); National Association of Health Data Organizations (2009); St Peters University Hospital, New Brunswick, New Jersey (2009); Massachusetts Hospital Association (2009); Cooper Health System, Camden, New Jersey (2009); Organizzato dal Laboratorio Management e Sanità Scuola Superiore Sant’Anna di Pisa (2010); Kentucky Academy of Family Physicians (2010); Southern Illinois University Health Policy Institute (2010); Ohio University College of Osteopathic Medicine (2009 and 2010); The Institute for Clinical Quality & Value (2010); The Marwood Group (2010); American Society of Clinical Oncologists (2010); OR Manager (2010); Delta Health Alliance (2010); SUNY Upstate University (2010); Intermountain Healthcare (2011); Canadian Health Services Research Foundation (2011); and Massachusetts Health Data Consortium (2011). In that same time period, he has received consulting fees from Vermont Department of Banking, Insurance, Securities and Health Care Administration; HealthDialog; Colorado Foundation for Medical Care; Seyferth Blumenthal & Harris; and American Medical Forensic Specialists.


1. Kunac DL, Kennedy J, Austin N, Reith D. Incidence, preventability, and impact of Adverse Drug Events (ADEs) and potential ADEs in hospitalized children in New Zealand: a prospective observational cohort study. Paediatr Drugs. 2009;11(2):153–160. [PubMed]
2. Kaushal R, Bates DW, Landrigan C, et al. Medication errors and adverse drug events in pediatric inpatients. JAMA. 2001;285(16):2114–2120. [PubMed]
3. Krähenbühl-Melcher A, Schlienger R, Lampert M, Haschke M, Drewe J, Krähenbühl S. Drug-related problems in hospitals: a review of the recent literature. Drug Saf. 2007;30(5):379–407. [PubMed]
4. Gu Q, Dillon CF, Burt VL. Prescription drug use continues to increase: U.S. prescription drug data for 2007-2008. NCHS Data Brief. 2010 Sept;(42):1–8. [PubMed]
5. Feudtner C, Dai D, Hexem KR, Luan X, Metjian TA. Prevalence of polypharmacy exposure among hospitalized children in the United States. Arch Pediatr Adolesc Med. [published online September 5, 2011] doi:10.1011/archpediatrics.2011.161. [PubMed]
6. Howard RF. Current status of pain management in children. JAMA. 2003;290(18):2464–2469. [PubMed]
7. Orsey AD, Belasco JB, Ellenberg JH, Schmitz KH, Feudtner C. Variation in receipt of opioids by pediatric oncology patients who died in children’s hospitals. Pediatr Blood Cancer. 2009;52(7):761–766. [PubMed]
8. Vanderweil SG, Tsai CL, Pelletier AJ, et al. Inappropriate use of antibiotics for acute asthma in United States emergency departments. Acad Emerg Med. 2008;15(8):736–743. [PubMed]
9. Kneyber MC, van Woensel JB, Uijtendaal E, Uiterwaal CS, Kimpen JL. Dutch Antibiotics in RSV Trial (DART) Research Group. Azithromycin does not improve disease course in hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease: a randomized equivalence trial. Pediatr Pulmonol. 2008;43(2):142–149. [PubMed]
10. Ermers MJ, Rovers MM, van Woensel JB, Kimpen JL, Bont LJ. RSV Corticosteroid Study Group. The effect of high dose inhaled corticosteroids on wheeze in infants after respiratory syncytial virus infection: randomised double blind placebo controlled trial. BMJ. 2009;338:b897. [PMC free article] [PubMed]
11. Hausner E, Fiszman ML, Hanig J, Harlow P, Zornberg G, Sobel S. Long-term consequences of drugs on the paediatric cardiovascular system. Drug Saf. 2008;31(12):1083–1096. [PubMed]
12. de Ferranti S, Ludwig DS. Storm over statins—the controversy surrounding pharmacologic treatment of children. N Engl J Med. 2008;359(13):1309–1312. [PubMed]