2025 Volume 10 Article ID: 20250022
In the realm of geriatric rehabilitation, pharmacotherapy is a double-edged sword: it is indispensable for managing comorbidities, yet is a frequent cause of falls, delirium, and functional decline that undermine recovery. This challenge is a global concern, addressed by foundational guidelines like the American Geriatrics Society Beers Criteria® and the European STOPP (Screening Tool of Older Person’s Prescriptions)/START (Screening Tool to Alert doctors to Right Treatment) criteria, both updated in 2023.1,2) In Japan, where a rapidly aging population makes this issue particularly pressing, two pivotal developments signal a significant advancement: the 2024 development of the Japan Anticholinergic Risk Scale (J-ARS)3) and the recent publication of the Guidelines for Safe Drug Therapy for Older Adults 2025.4) These new, culturally adapted tools provide a renewed mandate to move beyond simple risk mitigation. This editorial argues for a paradigm shift from a disease-centric model of pharmacotherapy to a function-centric model, one that actively seeks to maximize rehabilitation outcomes and enhance the quality of life for our older patients.
The current landscape of pharmacotherapy is fraught with prescribing errors of both commission (over-prescribing) and omission (under-prescribing). Errors of commission, such as polypharmacy and the use of Potentially Inappropriate Medications (PIMs), lead to a cascade of side effects that directly sabotage rehabilitation, including drowsiness, delirium, decreased motivation, dizziness, falls, and dysphagia.5,6) Conversely, errors of omission, or Potentially Prescribing Omissions (PPOs), involve the failure to prescribe clearly indicated, beneficial medications. Both error types are rampant and impede functional recovery, with evidence demonstrating an association between both over-prescribing and under-prescribing and functional disability in older patients.7) Compelling evidence from Japanese rehabilitation settings demonstrates this tangible harm. The high prevalence of polypharmacy and PIMs in stroke rehabilitation and their association with poor outcomes is well established.8) For example, psychotropic polypharmacy impairs walking independence in post-stroke patients,9) and in those with sarcopenia, the use of PIMs is negatively associated with functional recovery,10) with antipsychotic use in particular being linked to impaired muscle strength.11) Furthermore, statin use, another common PIM, also impairs muscle strength recovery in this population.12) Conversely, the benefits of medication optimization are increasingly clear. The value of deprescribing is supported by high-level evidence; a recent systematic review and meta-analysis confirmed that such interventions are effective in reducing polypharmacy and improving clinical outcomes.13) In line with this, studies from Japanese rehabilitation settings show that actively deprescribing psychotropic medications is directly associated with improvements in activities of daily living,14) and reducing polypharmacy is linked to improved energy intake,15) better functional recovery, and higher rates of home discharge.16) This confirms that inappropriate medications actively attenuate the gains made through intensive rehabilitation and that their removal can directly facilitate recovery. A particularly concerning issue is the high prevalence of drugs with anticholinergic properties. The cumulative anticholinergic burden is strongly associated with cognitive impairment, falls, dysphagia, and has recently been shown to impair urinary independence in post-stroke patients.17) The new J-ARS provides a crucial, standardized tool to quantify and manage this specific risk in daily practice.3)
Beyond simply avoiding harm, the future of pharmacotherapy in rehabilitation lies in proactively enhancing recovery through “rehabilitation pharmacotherapy,” using medications to synergistically boost therapy and leverage neuroplasticity.18) This potential is illustrated by the complex case of Selective Serotonin Reuptake Inhibitors (SSRIs) after stroke. Although criteria like STOPP caution against their use in patients with fall risk, recent meta-analyses confirm they can improve motor recovery without increasing overall adverse events.19) Traditional Japanese Kampo medicine offers another avenue; for instance, a systematic review showed hochuekkito is effective for frailty and anorexia, which are critical targets in rehabilitation.20) These examples, despite a lack of conclusive evidence for other agents like levodopa, provide a powerful proof of concept. They highlight the need for a nuanced, function-centric approach where medication choice, guided by a careful risk–benefit analysis, becomes an integral part of the rehabilitation strategy.
Achieving this new paradigm requires a multi-pronged strategy. First, clinicians must systematically manage medication risk using evidence-based tools. While international guidelines like the Beers Criteria1) and STOPP/START criteria2) provide a foundation, the development of Japanese-specific tools like the new J-ARS3) and the Guidelines for Safe Drug Therapy for Older Adults 20254) is a critical advancement for culturally adapted care. Integrating these tools to quantify risks like anticholinergic burden and to optimize prescribing is essential. Table 1 highlights common drug classes that warrant such careful review.
| Drug classification |
Drug (generic name) |
Target patients | Main side effects/ reasons for caution |
Recommended usage |
| Benzodiazepine receptor agonists | Zolpidem, eszopiclone, etizolam |
Patients with insomnia | Fall risk, delirium (impaired consciousness), daytime drowsiness, cognitive decline, dependency. Directly impairs rehabilitation participation and safety. | Avoid long-term use. Prioritize non-pharmacological interventions. If necessary, use the lowest effective dose for the shortest duration. Proactively deprescribe. |
| Antipsychotics | Haloperidol, risperidone,
quetiapine |
Patients with delirium or BPSD | Sedation (drowsiness, decreased motivation), extrapyramidal symptoms, falls, aspiration pneumonia (related to dysphagia), increased mortality. | Use only for severe symptoms unresponsive to non-pharmacological approaches. Use the lowest dose for the shortest duration, with a clear discontinuation plan. |
| NSAIDs | Loxoprofen, diclofenac,
celecoxib |
Patients with musculoskeletal pain | Renal impairment, gastrointestinal bleeding, fluid retention leading to unsteadiness. Can limit mobility and exercise tolerance. | Avoid routine, long-term use. Prefer acetaminophen or topical agents. If used, monitor renal function and for signs of bleeding. |
| Proton pump inhibitors | Omeprazole, lansoprazole, Esomeprazole | Patients with dyspepsia or for ulcer prophylaxis | Increased risk of fractures, Clostridioides difficile infection, pneumonia, micronutrient malabsorption potentially leading to weakness and decreased motivation. | Use for clear indications only (e.g., NSAID use, history of bleeding ulcer). Regularly review the need for continuation and attempt deprescribing. |
| First-generation antihistamines | Chlorpheniramine,
diphenhydramine |
Patients with allergies, pruritus, or insomnia (OTC) | Strong anticholinergic effects: sedation (drowsiness), confusion (impaired consciousness), dry mouth, constipation. High risk of delirium and falls. | Avoid use in older adults. Prefer second-generation non-sedating antihistamines (e.g., loratadine) or topical treatments. |
| Overactive bladder agents |
Solifenacin, imidafenacin, oxybutynin | Patients with urinary incontinence or neurogenic bladder (e.g., post-stroke) | Strong anticholinergic effects: delirium (impaired consciousness), cognitive decline, constipation, dry mouth (can worsen dysphagia). Impairs cognitive rehabilitation and increases fall risk. | Prioritize behavioral therapy. If medication is essential, consider agents with lower CNS penetration (e.g., trospium) or alternative mechanisms (e.g., mirabegron). Use the lowest effective dose. |
| Sulfonylureas | Glimepiride, gliclazide | Patients with type 2 diabetes | Prolonged hypoglycemia, leading to falls, confusion (impaired consciousness), and cognitive impairment. Risk is higher in patients with poor oral intake or renal dysfunction. | Prefer agents with lower hypoglycemia risk (e.g., DPP-4 inhibitors, metformin). If used, monitor blood glucose closely, especially around therapy times. |
| Opioid analgesics |
Tramadol, oxycodone, fentanyl |
Patients with moderate to severe pain | Sedation (drowsiness, decreased motivation), delirium, respiratory depression, severe constipation, increased fall risk. Directly interferes with cognitive and physical participation in rehabilitation. | Avoid routine use for chronic non-cancer pain. Use the lowest effective dose for the shortest duration for acute pain. Proactively manage constipation. |
| Gabapentinoids | Gabapentin, pregabalin |
Patients with neuropathic pain or seizures | Dizziness, drowsiness, unsteadiness (ataxia), peripheral edema, cognitive slowing. High fall risk, especially at initiation or dose titration. | Start with a very low dose and titrate slowly. Caution in patients with renal impairment. Assess risk–benefit, especially regarding fall risk vs. pain control. |
| Digoxin | Digoxin | Patients with heart failure or atrial fibrillation | Narrow therapeutic index. Toxicity can cause confusion (impaired consciousness), visual disturbances, arrhythmias, and weakness (decreased motivation, fall risk). | Use is rarely first-line. If used, maintain low serum concentrations (e.g., <0.9 ng/mL). Requires close monitoring of renal function and electrolytes. |
BPSD, Behavioral and Psychological Symptoms of Dementia; NSAIDs, non-steroidal anti-inflammatory drugs; OTC, over the counter.
Second, we must champion the role of the clinical pharmacist. As we have previously argued, optimizing complex medication regimens demands specialized expertise.21) Embedding clinical pharmacists in the rehabilitation team to lead medication reviews and deprescribing is a necessity, not an adjunct. The effectiveness of this model is supported by evidence showing improved medication safety and outcomes in vulnerable populations like hip fracture patients.22,23)
Third, we must advance the evidence for recovery-promoting agents. Although SSRIs show promise, the rehabilitation community must lead the charge in conducting high-quality, large-scale randomized controlled trials to establish the optimal use of these and other potential agents.
The time for passive acceptance of drug-related functional impairment is over. Armed with new national guidelines and risk assessment tools like the J-ARS, we must shift from a disease-centric prescribing model to a function-centric model. This is a call to action for the entire rehabilitation community: clinicians must adopt these new tools, institutions must integrate clinical pharmacists into every team, and researchers must build the robust evidence needed for pharmacologically enhanced recovery. By embracing this new paradigm, we can transform pharmacotherapy from a potential liability into a powerful asset for maximizing the functional independence and quality of life for every older adult we serve.
The authors declare no conflict of interest.
