Making A Difference Adverse Drug Reactions in Elderly People

A substantial cause of preventable illness

BMJ 2008; 336 doi: (Published 24 April 2008) Cite this as: BMJ 2008;336:956
  1. Jerry Avorn, professor of medicine and chief of division1,
  2. William H Shrank, instructor in medicine1
  1. 1Division of Pharmacoepidemiology and Pharmacoeconomics, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA 02120, USA
  1. Correspondence to: J Avorn javorn{at}

    Doctors should pay greater attention to managing the risk-benefit relationship to improve care of patients over 65, urge Jerry Avorn and William Shrank. The challenge of safer prescribing, says Anne Spinewine (doi: 10.1136/bmj.39520.686458.94), lies in shared decision making

    Patients over 65 years old bear the greatest burden of illness and thus are the greatest beneficiaries of drugs to prevent, ameliorate, or treat conditions. One of the most rapidly growing segments of the population, they consume an ever increasing proportion of all prescribed drugs. For decades elderly people were excluded from randomised trials of many preventive drugs, reinforcing scepticism over whether they would benefit from treatment of conditions such as hypercholesterolaemia and hypertension. But there is compelling evidence that elderly patients benefit from such treatments at least as much as their younger counterparts. In fact, because of the higher prevalence of preventable disease in older patients, they often derive greater benefits from such prescribing than younger patients. For this reason, much primary care has shifted from the treatment of acute illness to the management—often pharmacological—of “risk states” in elderly people, including hypertension, hypercholesterolaemia, and osteoporosis, as well as diseases such as atrial fibrillation, heart failure, and diabetes. Solid evidence from clinical trials indicates that appropriate prescribing can substantially reduce the burden of preventable morbidity in these conditions. Although such concerns are traditionally seen as a problem of the industrialised world, they are rapidly becoming a major issue facing developing countries as well.

    But this benefit comes at a price: the high prevalence of adverse drug reactions in older patients. The problem has several sources. One is the altered pharmacokinetic status of elderly people; they are less able to metabolise and excrete many common drugs, even in the absence of liver or kidney diseases. They may also have altered pharmacodynamic responses, with some receptor systems (such as those for opiates and benzodiazepines) having greater sensitivity with advancing age, and others (such as those for insulin) showing reduced sensitivity.1 Unfortunately, the under-representation of older patients (especially frail ones) in clinical trials makes it even harder for the prescribing doctor to anticipate and prevent untoward drug reactions in older patients.

    When an elderly person experiences an adverse drug reaction, it may be mistakenly attributed by the patient or doctor to a new disease or (even worse) the ageing process itself. Examples include the parkinsonian side effects of many antipsychotic drugs2 and the fatigue, confusion, or depression-like symptoms that can result from excessive use of heavily marketed psychoactive drugs. Elderly people are at special risk of such misattributions because of the pervasive cultural assumption that growing older brings with it a collection of inherent and inevitable disabilities. The problem is compounded by the slender preparation that most students receive in geriatrics and in clinical pharmacology, making the study of the proper use of drugs in elderly people a particularly neglected area.

    There is ample evidence of the clinical burden of iatrogenic illness in the elderly. Studies of US patients aged over 65 indicate that each year more than 180 000 life threatening or fatal adverse drug effects occur in the outpatient setting, of which over half may be preventable.3Another study attributed 6.5% of all hospitalisations in the general population to adverse drug events,4 a rate that is likely to be higher in elderly people.

    Despite these gloomy realities, the most notable aspect of drug induced illness in elderly people is the most encouraging. Once recognised, a side effect of a drug is probably the single most reversible affliction in all of geriatric medicine. Usually, care of elderly people requires the management of conditions with a downward course. But discovering that a symptom is caused by a drug presents an uncommon opportunity to effect a total “cure” by stopping the offending prescription or lowering the dose. In our own practices we have often seen patients on a seemingly inexorable trajectory towards institutional care whose functional capacity was restored by thoughtful reassessment of their drug regimens. This has led to the useful if overstated recommendation that “any new symptom in an older patient should be considered a possible drug side effect until proved otherwise.”

    As well as being alert to the possibility of new iatrogenic problems, it is also prudent to reassess a patient’s entire drug regimen at least twice a year, including categories often overlooked by patients and doctors: drugs bought over the counter and “nutraceuticals” such as herbal remedies or dietary supplements. Although these products are often devoid of therapeutic benefit, they can impose important toxicities, and their interactions with prescribed drugs are poorly understood. With growing use of the electronic medical record, we can expect that drug regimen review will increasingly be prompted by the computer in the course of routine care. In one computerised system for entering prescription orders, the system automatically checks all prescribed drugs and dosages against the age of the patient and recommends a lower dose or different drug if necessary.5

    Non-compliance with prescribed drug regimens can produce a different kind of drug related morbidity. In this “silent epidemic,” as much as half of prescribed drugs are simply not taken.6 Considerable morbidity results from this other kind of drug related illness in elderly people, in which potentially useful treatments are not taken or (because of misplaced therapeutic nihilism) not prescribed in the first place.7 8

    Broader systems based and educational approaches are emerging to guide the evidence based use of drugs in older patients so as to reduce their burden of iatrogenic illness while ensuring that needed drugs are prescribed properly.9 Better attention to managing this benefit-risk relationship will play an increasingly important role in maintaining and improving the health of an ageing population.10


    • Competing interests: None declared.

    • Provenance and peer review: Commissioned; not externally reviewed.


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