Polypharmacy in Older Adults

SPECIAL REPORT: POLYPHARMACY

Older adults, defined as individuals older than 65 years, are vulnerable to drug-induced adverse effects due to age-related physiological changes, such as decreased renal and hepatic function, increased body fat, lower total body water, and lower lean body mass, all of which can impact the pharmacodynamics and pharmacokinetics of medications and increase the elimination half-life.¹ Older adults experience a higher prevalence of comorbid chronic conditions, such as diabetes, heart disease, arthritis, and other psychiatric conditions. Nearly 95% of older adults have at least 1 chronic condition, and nearly 80% have 2 or more.¹ Polypharmacy is common given multiple medical comorbidities, but exposure to multiple medications may further lead to harm due to inappropriate medication prescription.²

The World Health Organization defines polypharmacy as “the administration of many drugs at the same time or administration of an excessive number of drugs.”³ Surprisingly, there is no consensus on the medication threshold and definition of polypharmacy. However, it is commonly described as the concomitant use of 5 or more medications.³ For older adults, polypharmacy can be associated with increased poor health outcomes due to increased risk of falls, drug-drug or drug-supplement interactions, medication nonadherence, hospitalizations, and death.² Findings from a recent meta-analysis examining the prevalence of polypharmacy and factors associated with polypharmacy showed that individuals older than 65 years had a higher prevalence of polypharmacy when compared with data from studies with individuals younger than 65. Additionally, there were lower estimates of polypharmacy in community settings when compared with outpatient and hospital settings, with overall results showing that older age and inpatient settings were associated with a higher prevalence of polypharmacy.²

Although consensus is unclear on the definition of polypharmacy in psychiatry, one common definition is the use of 2 or more psychiatric medications, further broken down into categories (eg, 2 or more medications of the same class, multiclass, adjunctive, augmentation, and total pharmacy). The estimated prevalence of polypharmacy in older adults hospitalized for psychiatric illness/disorders is as high as 80%.⁴ Not surprisingly, findings from a recent study examining the rates of polypharmacy in older adults with and without dementia showed that the median number of medications for adults with dementia was 8, compared with 3 in those without dementia.⁵ Similarly, data from a meta-analysis examining the association between polypharmacy and depression showed an increased prevalence of polypharmacy in individuals with depression.⁶ Older adults with psychiatric comorbidities are particularly vulnerable to polypharmacy and adverse outcomes. In clinical practice, it is often challenging to avoid polypharmacy, particularly in older adults with treatment-resistant diagnoses necessitating augmentation strategies that would require multiple psychotropic medications. However, using the fewest possible medications and the simplest dosing regimen can help reduce the number of drugs prescribed, along with ongoing evaluation of indication, drug-drug interactions, and linking of each medication with a diagnosis.

Overall, research findings have indicated that inappropriate polypharmacy can affect up to one-third of the population, with polypharmacy becoming a substantial health care burden associated with an estimated cost of $50 billion in the United States.² Therefore, it is imperative to prevent adverse events associated with polypharmacy, identify individuals who are at high risk of receiving inappropriate polypharmacy, and take steps toward deprescribing if possible.

Criteria and Screening Tools

Explicit criteria and tools have been created to support the deprescribing of inappropriate medications and to reduce the prevalence of polypharmacy in older adults. Mark Beers, MD, and colleagues initially developed the Beers Criteria in the US in 1991 to identify medications for which the potential harm outweighed the expected benefits for nursing home residents.⁷ Over time, the criteria have been revised and updated by the American Geriatrics Society (AGS), expanding to include all older adults in ambulatory, acute, and institutionalized settings of care, except hospice and end-of-life care settings. The Beers Criteria is now used widely by clinicians, educators, researchers, health care administrators, and regulators, and although the list can be used internationally, it is specifically designed for use in the US. The updated 2023 Beers Criteria organizes potentially inappropriate medications (PIMs) by organ system and therapeutic category, outlines PIMs that should be used with caution, highlights clinically important drug-drug interactions, and describes medications that require renal dose adjustments.⁸

In addition to the Beers Criteria, the Screening Tool of Older Persons’ Prescriptions and Screening Tool to Alert to Right Treatment (STOPP/START) criteria were developed in Ireland by O’Mahony et al in 2008 and are used predominantly in Europe.⁴ Data from an earlier study comparing the Beers Criteria with the STOPP/START criteria suggest that the STOPP/START criteria may be more sensitive because they account for therapeutic duplication and potential prescribing omissions, therefore identifying a significantly higher proportion of patients requiring hospitalization as a result of PIM-related adverse events when compared with the Beers Criteria.⁹ However, most of the studies conducted in which STOPP/START was applied were specific to an inpatient psychiatric setting compared with the wider application of the Beers Criteria in multiple settings outside the hospital and predominantly used in the US.⁴

Deprescribing and Reducing

As individuals age, medications that were previously necessary, effective, and safe require reevaluation due to physiological and functional changes (ie, dementia, chronic comorbidities) that may shift the balance of benefits and harms. Additionally, there is increasing evidence that the benefits of many medications, particularly preventive medications, may be more harmful than beneficial with advancing age (eg, strict glycemic or blood pressure control). Therefore, it is imperative to reassess health care goals and priorities, as many older adults may want to shift their focus to comfort and maximizing quality of life.¹⁰

Deprescribing is a suggested intervention to reverse potentially iatrogenic harms of inappropriate polypharmacy and is defined as “the process of withdrawal of inappropriate medication, supervised by a health care professional, with the goal of managing polypharmacy and improving outcomes.”¹¹ The Figure summarizes a potential approach to deprescribing.

However, results of a meta-analysis showed limited evidence to support deprescribing as an intervention that reduced mortality in randomized studies.¹² Findings from the same study also showed that mortality was significantly reduced when applying patient-specific interventions to deprescribing, suggesting that a more tailored, individual approach may be necessary for more class-specific deprescribing, such as with psychotropic and anxiolytic/hypnotic medications.

Many studies have examined the importance of deprescribing certain psychotropic medications in older adults, particularly antipsychotics and anxiolytic/hypnotic medications. In particular, antipsychotic medications are frequently used to treat behavioral and psychological symptoms of dementia (BPSD), especially in long-term residential care settings. Antipsychotics carry an FDA black box warning for increased mortality in older adults and are listed on the Beers Criteria as a medication to be avoided. Data from many studies have shown that deprescribing antipsychotics in older adults with dementia did not result in worsening BPSD or adverse outcomes, suggesting that ongoing reevaluation and gradual dose reduction must be considered in these patient populations.¹³ Additionally, findings from another randomized control trial indicated that a systematic review of medications conducted in nursing homes reduced psychotropic drug prescriptions without worsening BPSD symptoms and improved level of functioning.¹⁴ Unfortunately, most studies focus on addressing inappropriate polypharmacy in older adults with dementia in long-term care facilities and have not extensively studied deprescribing in more outpatient-based settings to include the individual and their caregiver.¹⁴

Additionally, it is well known that benzodiazepines (BZDs) and the related hypnotic Z-drugs are harmful for older adults and can result in increased risk of falls, fractures, cognitive impairment, car crashes, and more. Unfortunately, deprescribing BZDs is more challenging than antipsychotics due to complex interactions among patients, physicians, and concerns about distressing but rarely fatal withdrawal syndrome.¹⁵ A recent review of deprescribing BZDs in older adults showed variable success rates in deprescribing, ranging from 27% to 80%, likely attributable to differing approaches that ranged from interventions targeting patient and/or caregivers and providing additional resources to the patient (eg, gradual dose reduction [GDR] with relaxation techniques, sleep hygiene, cognitive behavioral therapy). These interventions can be effective if the patient is motivated to cease taking the medication and does not have significant cognitive impairment, but prescribing interventions that include audits, algorithms, medication review, and supervised GDR may also be helpful additions for physicians to feel more comfortable deprescribing BZDs and related Z-drugs.¹⁵ For example, for patients in more advanced stages of dementia in which they exhibit neuropsychiatric and behavioral symptoms, antipsychotics may be needed to manage behavioral symptoms that have not responded to other interventions despite antipsychotics carrying an FDA black box warning for increased risk of mortality in patients older than 65 years with dementia.¹⁶ For some older adults, it may be impossible to avoid certain medications that may otherwise be contraindicated, and extensive discussion around goals of care, life expectancy, and potential drug-drug interactions and adverse effects are necessary with the patients and family/caregivers when assessing medication indications and their risks and benefits. (See “Strategies for Reducing Polypharmacy in Older Adults” in this article.)

Concluding Thoughts

Ultimately, more deprescribing intervention studies are needed given the complexity of interventions utilized and the variability of implementation of deprescribing in clinical practice across different health care settings. Deprescribing interventions will need to be tailored to individuals with more target-specific goals to be beneficial, but further studies are needed to determine if there are also unintended consequences to deprescribing.

With the recent push discouraging the use of and making it difficult to prescribe antipsychotic and psychotropic medications in long-term care, culminating in the recently passed California law making the prescribers of psychotropic medications (except for antidepressants) legally responsible at the level of misdemeanor for prescribing without documented written consent, many older patients with severe mental illness or behavioral disturbances due to dementia may be left without necessary treatment for severe psychiatric symptoms, which will ultimately lead to greater suffering and caregiver burden. Clinicians should carefully weigh the risks and benefits of each prescribed medication for an older adult with neuropsychiatric diseases and periodically review all prescribed medications and over-the counter supplements and herbal remedies, and discontinue those that are unnecessary and potentially harmful.¹⁷

Dr Nguyen is an assistant clinical professor in the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, at the University of California, Los Angeles (UCLA). She is also associate program director of the UCLA Psychiatry Residency Training Program and associate director of the UCLA Integrative Psychiatry Clinic. Dr Oughli is an assistant clinical professor in the Department of Psychiatry and Biobehavioral Sciences at the University of California, Los Angeles. Dr Lavretsky is a professor in residence in the Department of Psychiatry at the University of California, Los Angeles. She is president of the American Association for Geriatric Psychiatry, a distinguished fellow of the American Psychiatric Association and the American Association for Geriatric Psychiatry, and a fellow of the American College of Neuropsychopharmacology. She is also on the Editorial Board of Psychiatric Times.

References

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