When Do Medication Risks Outweigh Benefits in Older Adults?

An older woman in her eighties with moderate Alzheimer’s disease developed limb rigidity, shuffling gait, excessive salivation, and recurrent falls after her risperidone dose was progressively increased to treat delirium associated with an infection. The symptoms were caused by drug-induced parkinsonism. After risperidone was discontinued under medical supervision, she resumed eating and walking within a month.In primary care settings across Brazil, 22%-54% of older adults are prescribed one or more potentially inappropriate medications (PIMs).Speaking with Medscape’s Portuguese edition, Eduardo Canteiro Cruz, MD, a geriatrician from the Escola Paulista de Medicina of the Federal University of São Paulo in São Paulo, Brazil, and administrative director of the Brazilian Society of Geriatrics and Gerontology (SBGG) in Rio de Janeiro, Brazil, described the case as an example of a broader problem in the care of older adults. Other specialists highlighted the challenges of identifying PIMs, reducing prescribing risks, and making deprescribing safer for older adults.“The use of PIMs and the lack of awareness regarding their use and the consequences they may entail are extremely serious problems in the care of older adults in Brazil,” said Leonardo Brandão de Oliva, MD, president of the SBGG. “Although widely recognized tools exist, their practical use by nonspecialist physicians still falls far short of what is necessary. There is a significant gap in academic training: General pharmacology is taught, but there is almost no training in applied geriatric pharmacology.”According to data from the Brazilian Medical Demographics 2025 survey, Brazil has only 3167 geriatricians. Therefore, most older adults receive care from general practitioners, cardiologists, neurologists, and family physicians. Brief consultations, fragmented care across multiple specialties, and limited longitudinal follow-up can contribute to prescribing cascades in which additional medications are prescribed to treat adverse effects caused by existing drugs instead of prompting a review of the original treatment.Age-related changes in pharmacokinetics make the standard medication regimens used in younger adults more likely to cause orthostatic hypotension, excessive sedation, and delirium in older adults. Three medication classes deserve particular attention.Benzodiazepines and Z-drugs, including clonazepam, alprazolam, and zolpidem, are widely prescribed for insomnia and anxiety, despite their association with cognitive decline and falls.Bruno Simas da Rocha, PharmD, PhD, clinical pharmacist at the Hospital de Clínicas de Porto Alegre in Porto Alegre, Brazil, and specialist in gerontology certified by the SBGG, warned that combining these medications with opioids or other central nervous system depressants substantially increases the risk for respiratory depression and fractures.Medications with a high anticholinergic burden, including first-generation antihistamines, muscle relaxants, tricyclic antidepressants, and antimuscarinic drugs for overactive bladder, can also impair cognitive function and intestinal motility. Cumulative exposure can lead to confusion, urinary retention, and severe constipation.Nonsteroidal anti-inflammatory drugs and antiplatelet agents prescribed for primary prevention are important contributors to bleeding and kidney injury. In 2022, the US Preventive Services Task Force recommended against initiating acetylsalicylic acid for the primary prevention of cardiovascular events in adults aged 60 years or older because the small potential benefits are outweighed by the risk for gastrointestinal and intracranial bleeding.This position is consistent with the 2023 American Geriatrics Society Beers Criteria and version 3 of the Screening Tool of Older Persons’ Prescriptions/Screening Tool to Alert to Right Treatment criteria.Cruz proposed a straightforward way to identify a prescribing cascade in clinical practice: “The first sign of a prescribing cascade is the onset of a new symptom temporally associated with the introduction of a medication in a patient who had previously been stable. We must establish the premise that any new symptom in an older adult may be, until proven otherwise, a side effect of a medication.”A Structured Approach to DeprescribingBecause frailty and comorbidities accumulate, the balance between therapeutic benefits and treatment burden can shift. Among older adults taking 10 or more medications, a situation known as hyperpolypharmacy, the prevalence of potentially inappropriate prescriptions exceed 80%.“Quality of life and survival should take precedence over chronological age,” said Ricardo Shoiti Komatsu, MD, PhD, geriatrician, professor, and head of the Department of Geriatrics and Gerontology at the Faculty of Medicine of Marília (FAMEMA) in Marília, Brazil. He is a supervisor of FAMEMA’s geriatric medicine residency program.“The risk-benefit threshold changes dramatically when the patient’s life expectancy becomes shorter than the time required to obtain the therapeutic benefit of the medication.”Komatsu cited bisphosphonate treatment in older adults with frailty who are bedridden as an example. The immediate risk for esophagitis may outweigh the potential benefit of preventing fractures over a longer period.Similarly, prescribing statins for primary prevention to individuals with a life expectancy of less than 2 years or pursuing extremely strict glycemic and blood pressure targets in vulnerable older adults may expose them to immediate risks, including hypoglycemia, orthostatic hypotension, and syncope, which outweigh potential long-term benefits.Deprescribing, however, should not lead to undertreatment. “We cannot fall into the opposite error of failing to prescribe essential medications simply because of age,” warned Milton Roberto Furst Crenitte, MD, PhD, geriatrician and coordinator of the Sexuality and Ageing Clinic at Hospital das Clínicas of the University of São Paulo’s Faculty of Medicine in São Paulo. “Depriving an older adult with atrial fibrillation of an anticoagulant to prevent a stroke or failing to treat osteoporosis in someone with good functional status is a mistake. What determines the course of action is the triad of clinical indication, functional status, and the individual’s prognosis.”High-risk medications, particularly benzodiazepines and opioids, should not be discontinued abruptly because doing so can cause severe withdrawal symptoms, rebound effects, and recurrence of the underlying condition. Gradual dose reduction requires a plan developed with the patient and caregivers, with support from clinical pharmacy services when available.Two tools can help clinicians make deprescribing decisions more systematically. The Confirm, Estimate, Assess, Sort, Eliminate protocol is a structured deprescribing framework designed to guide clinicians through sequential steps when reviewing and reducing inappropriate polypharmacy in patients who are old or those with frailty.The Seek, Help, Assess, Reach, Evaluate model complements this approach by promoting shared decision-making, allowing clinicians to incorporate patients’ values and preferences into treatment decisions.Clinicians must also consider the risk of splitting tablets incorrectly during dose tapering. “Extended-release or enteric-coated tablets should never be split. When small, precise dose reductions are necessary, a safe strategy is to switch to liquid formulations, available for various benzodiazepines and antidepressants, or to use customized compounding,” Rocha said. Written tapering schedules and monitoring every 2 weeks during the first few weeks can help clinicians distinguish temporary withdrawal symptoms from recurrence of the underlying condition.Communication and Continuity of CareFamily members may interpret discontinuing medication as giving up on treatment or neglecting older adults. Cruz advised clinicians to explain the biological changes associated with aging. “The most effective argument is to explain that the body changes over time. An 80-year-old’s body does not function in the same way as that of a 60- or 40-year-old, and a medication that was helpful in the past may become harmful now,” he said.Another challenge is the “boomerang effect” after hospital discharge. A deprescribing plan established in outpatient care may be reversed when an older adult is hospitalized for an acute illness and discharged with new prescriptions for sedatives, anxiolytics, and proton pump inhibitors.To reduce this risk, Komatsu and Crenitte recommended giving caregivers a formal deprescribing card or prescription that explained why a medication was discontinued and the harm it caused. They also advised arranging a care transition appointment and medication review within 7-14 days after discharge.When a geriatrician or general practitioner identifies a medication prescribed by another specialist as inappropriate, direct communication with the prescribing physician is essential. “The approach should be cooperative: Contact the attending physician to explain the patient’s current functional status and suggest a joint reevaluation, without ever disparaging the previous course of action or undermining the patient’s trust in their physician,” Crenitte said.The same collaborative approach applies when replacing medication with nonpharmacologic strategies for conditions such as insomnia, anxiety, and osteoarticular pain. “Through muscle strengthening with physical therapy and physical education, we’ve been able to substantially reduce the use of pain relievers and anti-inflammatory drugs in patients with knee osteoarthritis,” de Oliva said. Clinicians should prescribe sleep hygiene measures and behavioral therapies with the same rigor that they apply to medication regimens.“Technology, electronic health records, and digital apps for monitoring anticholinergic burden are valuable tools for raising alerts in day-to-day practice, as long as they are configured to prevent alert fatigue,” Komatsu concluded. “But no software can replace face-to-face contact. Prescribing and discontinuing medications are deeply human acts that require active listening, empathy, and the building of a bond of trust between the doctor, the patient, and the patient’s family.”Daniela Barros is a Brazilian journalist specializing in social journalism at the Pontifical Catholic University of São Paulo in São Paulo and is a master’s student in the Department of Social Medicine at the Ribeirão Preto Medical School in Ribeirão Preto, Brazil. She has been involved in medicine for 23 years and has contributed to several specialized publications.This story was translated from Medscape’s Portuguese edition.