Polypharmacy in the Elderly: How to Reduce Adverse Drug Events

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Psychotropic drugs

Another often-prescribed medication group is psychotropic drugs, specifically antipsychotics and benzodiazepines, for agitation and behavioral disturbances in dementia. A year-long study of 851 patients in two long-term care nursing homes in Boston found that risk for ADRs—specifically, falls—was increased in those who had a change (initiation or dose increase) in psychotropic medication (ie, benzodiazepine, antipsychotic, or antidepressant).12

Second-generation antipsychotics, which are more commonly prescribed than first-generation agents, work on a postsynaptic blockade of brain dopamine D2 receptors and have an increased affinity for serotonin 5-HT2A receptors (see Table 1 for pharmacology of these medications).13,14 Adverse effects of these drugs include hypotension, sedation, and anticholinergic effects. Second-generation antipsychotics also carry a “black box warning” for increased risk for death in elderly patients with dementia-related psychosis.15

Pharmacology of Commonly Prescribed Antipsychotics image

Benzodiazepines bind to receptors in the gamma-aminobutyric acid receptor complex, which enhances the binding of this inhibitory neurotransmitter (see Table 2 for pharmacology). Of this class of drugs, lorazepam has the highest potency, whereas midazolam and diazepam have lower potencies. Use of benzodiazepines increases risk for delirium and respiratory depression.16

Pharmacology of Commonly Prescribed Benzodiazepines image

Diabetes treatment

People with diabetes have an increased risk for ADEs; this risk is elevated in older adults due to comorbidities such as peripheral neuropathy, retinopathy, coronary artery disease, and peripheral vascular disease.10 Hypoglycemic agents, such as insulin and insulin secretagogues, confer a higher risk for falls due to their hypoglycemic effect.10 Furthermore, metformin is known to increase risk for cognitive impairment in patients with diabetes.10


Predicting and preventing ADEs should be a health care provider’s priority when treating an elderly patient taking multiple medications—but it is often overlooked. Electronic medical records (EMRs) are helpful in preventing ADEs, specifically prescription errors, by flagging the patient’s chart when potentially problematic medications are ordered; however, this captures only a portion of ADEs occurring in this popu­lation.7

Other options to evaluate a patient for polypharmacy and possible ADRs include the Beers Criteria and the STOPP/START Criteria.17,18 Additionally, performing thorough and frequent medication reviews helps ensure that patients are prescribed essential medications to treat their comorbidities with the most opportunistic risk-benefit ratio. Patients’ medication lists across settings (eg, hospital, primary care, urgent care) can be accessed more easily, efficiently, and accurately with the integration of EMRs.

Beers Criteria

First published by Dr. Mark Beers in 1991 and endorsed by the American Geriatrics Society, the Beers Criteria identifies possible harmful effects of certain commonly prescribed medications to help guide and modify pharmacologic treatments, particularly in adults older than 65. The Beers Criteria classifies medications into three categories:

  1. Drugs that should be avoided or dose-adjusted
  2. Drugs that are potentially inappropriate in patients with certain conditions or syndromes
  3. Drugs that should be prescribed with caution in older adults.17

In the most recent update (2015), possible adverse effects of medications based on a patient’s hepatic or renal function, the effectiveness of the medication, and possible drug interactions were added. For example, nitrofurantoin and antiarrhythmics (eg, amiodarone and digoxin) should be avoided at a lower threshold of hepatic and renal impairment than previously recommended. The criteria suggest avoiding use of zolpidem, a nonbenzodiazepine receptor agonist, because of its elevated risk for adverse effects and minimal effectiveness in treating insomnia. More information about the 2015 criteria is available from the American Geriatrics Society (http://online library.wiley.com/doi/10.1111/jgs. 13702/full).19

The latest update also takes into account recently published evidence of increased ADEs resulting from drugs such as antipsychotics and proton pump inhibitors (PPIs).20 Antipsychotics are associated with an increased risk for morbidity and mortality, and PPIs are now recommended only for treatment duration of up to two months because of the possible increased risk for Clostridium difficile infection, as well as falls and fractures in patients older than 65.20 (PPIs indirectly reduce calcium absorption, which may lead to an increased fracture risk, particularly in postmenopausal women.20)

As with any guideline, the Beers Criteria was designed to supplement, not replace, clinical expertise and judgment. The risks and benefits of a medication should be weighed for the individual patient.


Less widely used is the STOPP/START Criteria, an evidence-based set of guidelines consisting of 65 STOPP (Screening Tool of Older Person’s potentially inappropriate Prescriptions) and 22 START (Screening Tool to Alert doctors to the Right Treatment) criteria. Although they may be used individually, STOPP and START are best used together to determine the most appropriate medications for an elderly patient.

The STOPP guidelines help determine when the risks of a medication may outweigh the benefits in a given patient. STOPP includes recommendations for the appropriate length of time to use a medication; for example, PPIs should not be used for more than eight weeks (similar to the Beers recommendation) and benzodiazepines and neuroleptics for more than four weeks.18

START helps clinicians recognize potential prescribing omissions and to identify when a medication regimen should be implemented based on a patient’s history.18 Examples of START criteria include suggestions of when to initiate calcium and vitamin D supplementation for prevention of osteoporosis and when to begin statins in patients with diabetes, coronary artery disease, and cardiovascular disease.18

STOPP/START is organized by physiologic system, which allows for greater usability, and it addresses medications by class rather than specific medications. (The Beers Criteria was criticized for these reasons, as well as its limited transferability outside the United States.) When assessed in systematic reviews, the STOPP/START criteria were found to be fundamentally more sensitive than the Beers Criteria. Overall, it was concluded that the use of the STOPP/START criteria resulted in an absolute risk reduction of 21.2% to 35.7% and greatly improved the appropriateness of prescribing medication to the elderly. Its use also resulted in fewer follow-up appointments with a primary care physician (PCP).18

iPhone and Android applications such as iGeriatrics and Medstopper provide clinicians with easy access to Beers Criteria and STOPP/START Criteria, respectively.

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