We are excited to present this themed issue on rational prescribing and deprescribing of medications in older adults with an increased fall risk. Fall-risk-increasing drugs (FRIDs) are widely prescribed to older adults: 65–93% of older adults with fall-related injury use at least one FRID [1]. Literature shows that a medication review and appropriate deprescribing is one of the most effective components of the multifactorial fall-preventive intervention [2]. The recently published World Guidelines for Falls Prevention and Management [3], therefore, recommend performing a comprehensive medication review as part of a multifactorial falls prevention program. An important component in this assessment constitutes a comprehensive medication review for weighing the benefits and harms of prescribed medications for the individual patient. Yet, in clinical practice, managing polypharmacy and deprescribing FRIDs after a fall incident in older adults is often highly challenging, and less frequently performed than expected [1, 4,5,6]. In part, this is explained by health care professionals being reluctant to deprescribe medications in general [7, 8], and FRIDs in particular [5, 9]. The need to improve rational pharmacotherapy of high-risk medications in older, multimorbid adults at risk of falling has motivated us to write this themed issue on (de)prescribing FRIDs. We provide the practicing clinician with practical resources, tools, tips, and tricks for safe FRID (de)prescribing, minimizing adverse drug reactions, and achieving optimal risk benefit ratio for individual patients.

In the first paper of this issue, written on behalf of the EuGMS T&F group on FRIDs, Nathalie van der Velde and Lotta Seppala et al. [10] outline the group's position on the implementation and execution of the recommendations for preventing medication-related falls, as formulated in the recently published World Guidelines for Falls Prevention and Management [3]. The authors advocate integrating the medication review as part of a comprehensive geriatric assessment to produce a personalized and patient-centered assessment.

The special issue also comprises six clinical reviews that offer comprehensive insights into the indications for prescribing FRIDs, their efficacy, reasons for deprescribing, and proposed approaches for deprescribing. These reviews encompass practical steps, including monitoring recommendations, and discuss both pharmacological and non-pharmacological alternatives that promote safety. The reviews also present detailed overview tables that semi-quantitatively summarize the propensity of FRIDs to cause fall-related adverse effects, such as orthostatic hypotension and electrolyte abnormalities. These tables highlight variations in adverse effect profiles among different FRIDs or subclasses, and even within subclasses. These distinctions in the propensity to contribute to fall risk can facilitate individualized decision-making, enabling clinicians to choose the most suitable medication to initiate or switch to a safer alternative based on specific patient characteristics. Additionally, the reviews equip clinicians with practical tools and resources for safe (de)prescribing of FRIDs, particularly in scenarios involving deteriorating kidney function.

In their clinical review on diuretics and SGLT2 inhibitors in heart failure patients, Eveline van Poelgeest and colleagues [11] present an informative clinical case featuring an older heart failure patient who is at a high risk of falling. They highlight the clinical dilemma surrounding the (de)prescribing of diuretics in such patients. The authors emphasize that older individuals with heart failure are generally highly susceptible to falls, and the use of diuretics and SGLT2 inhibitors for heart failure treatment may potentially contribute to various fall-related adverse effects. While there are some overlap** fall-related adverse effect profiles between these two drug classes (such as the tendency to induce hypotension), the authors also draw attention to important distinctions. According to the currently available evidence, SGLT2 inhibitors demonstrate potential beneficial disease-modifying effects, including those related to heart failure and renal protection, whereas diuretics primarily provide symptomatic relief. Albeit also SGLT2 inhibitors potentially increase fall risk, the authors illustrate a more favorable fall-related adverse effect profile for SGLT2 inhibitors compared to diuretics. Their analysis reveals not only differences between diuretics and SGLT2 inhibitors but also variations within diuretic subclasses and even within individual subclasses.

In their clinical review on antipsychotics and fall risk, Miia Tiihonen et al. [12] draw attention to the growing off-label use of antipsychotics in older adults for treating neuropsychiatric symptoms associated with dementia, despite the well-known potential for adverse events. The authors demonstrate that antipsychotics elevate the risk of falls through various mechanisms linked to their receptor profiles and the risk of ischemic stroke. They recommend reserving antipsychotics as a last resort when other treatment options have proven ineffective, or when severe agitation or the potential for harm to the patient and/or others exists. Furthermore, they advocate for using the lowest effective dose for the shortest possible duration. Additionally, the authors present a separate table containing information on CYP-enzyme pathways and recommendations based on pharmacogenetic patient profiles. This information can be valuable in making personalized decisions regarding specific antipsychotic medications.

In their clinical review on benzodiazepines (BZDs) and Z-drugs (zolpidem, zopiclone, and zaleplon), Andreas Capiau et al. [13] explore the therapeutic challenges faced when treating patients with both an increased risk of falls and insomnia or anxiety disorders. The authors highlight the varying fall-related adverse effect profiles of BZDs and Z-drugs. They advocate for the prescription of these medications only when there is a clear indication, emphasizing the importance of utilizing the lowest effective dose and limiting the duration of use as much as possible. The authors also recommend considering non-pharmacological alternatives with proven efficacy, such as cognitive-behavioral therapy for insomnia (CBT-I). They emphasize the need for cautious deprescribing, as it may be easier to avoid initiating these drugs initially than to discontinue their use, particularly due to the potential risk of withdrawal symptoms following long-term use.

In their clinical review on antimuscarinics for overactive bladder (OAB) or alpha-blockers for benign prostatic hyperplasia (BPH) in older adults at risk of falls, Birkan Ilhan et al. [14] illustrate the clinical challenge arising from the interplay between untreated urinary incontinence, overactive bladder, and the medications employed to address these conditions, all of which contribute to fall risk. The authors shed light on the adverse effect profiles of these medications, which include fall-related adverse effects, as well as their potential for drug–drug and drug–disease interactions. As a result, they caution against the inappropriate ongoing use of these medications if symptoms do not ameliorate despite treatment.

In their clinical review on cognitive enhancers in dementia, specifically memantine and acetylcholinesterase inhibitors, Gabbie Portlock et al. [15] elucidate the considerable challenges involved in decision-making regarding these medications for patients experiencing falls. The authors highlight that cognitive impairment represents a significant risk factor for falls, with individuals with dementia having a twofold increased risk compared to those with intact cognition. They also emphasize that the long-term cognitive and behavioral benefits of cognitive enhancers are not unequivocal. To address these challenges, the authors raise awareness of cognitive stimulation therapy (CST) as a reasonable alternative for individuals with mild-to-moderate dementia when cognitive enhancers are contraindicated, or deemed inappropriate (e.g., individuals with a history of unexplained syncope). They provide a summary of fall-related adverse effects associated with these medications and present reasons for deprescribing them in cases of high fall risk, while cautioning about potential worsening of neuropsychiatric symptoms upon deprescribing. Additionally, the authors highlight that evidence in the literature suggests that cholinesterase inhibitors may help reduce fall risk in patients with Alzheimer's dementia by improving gait.

In their clinical review on alpha-blockers for hypertension and centrally acting antihypertensives such as methyldopa and clonidine, Tomas Welsh et al. [16] highlight that these drug classes have the least extensive evidence base for assessing morbidity and mortality compared to other antihypertensive medications. Moreover, they are associated with a high risk of significant falls and non-fall-related side effects. Consequently, their use in older adults at risk of falling should be limited to patients with treatment-resistant hypertension, and only as add-on therapy and in line with patient goals. To assist clinicians in making informed clinical decisions, the authors provide a comprehensive deprescribing algorithm specifically designed for alpha-blockers and centrally acting antihypertensives.

Two clinical reviews in this series preceded this special issue. In their paper on opioids, Roosa-Emilia Virnes et al. [17] demonstrate that opioids contribute to an increased risk of falls by inducing drowsiness, (orthostatic) hypotension, and hyponatremia in the case of weak opioids. The authors strongly advocate for the cautious prescription of opioids to older individuals who are at a high risk of falls, emphasizing that they should only be prescribed to achieve adequate pain control, and thus for improvement of quality of life. Furthermore, they emphasize the importance of regularly re-evaluating the need for continued opioid use, and highlight the consideration of deprescribing or adjusting to a lower dosage or safer alternative if the patient's clinical condition allows.

In their clinical review on antidepressants, van Poelgeest et al. [18] draw attention to the fact that fall risk is influenced not only by the use of antidepressants but also by untreated depression itself. The authors highlight that while antidepressants are equally effective in managing depression, they exhibit notable differences in terms of their fall-related side-effect profiles. The authors provide the reader with detailed insight in fall-related side-effect profile of the different antidepressants, and explain the importance of a patient-centered thorough risk/benefit evaluation for decisions to continue or withdraw antidepressants in older people who are at increased risk of falling.

We conclude this special issue with two narrative review papers addressing the dilemmas of (de)prescribing osteoporosis drugs and anticoagulants. Although these drug classes lack effects that contribute to fall risk, they are of relevance to clinicians managing older adults who are susceptible to falls, as they do affect the risk of fall-related injuries. In their systematic review, Ditte Beck Jepsen et al. [19] examined the extent to which international osteoporosis guidelines incorporate deprescribing recommendations for bisphosphonates. This evaluation is crucial, because advanced age, declining health status, and evolving benefit-risk profiles necessitate cautious use of preventive medications like bisphosphonates in older individuals, including considering deprescribing as an option. Out of the 42 guidelines analyzed, 76% included deprescribing recommendations, but practical guidance on how to make personalized deprescribing decisions based on individual health contexts was generally lacking.

In their paper addressing the utilization of anticoagulants in older adults with an increased risk of falls, specifically for atrial fibrillation or venous thrombosis, Anneka Mitchell et al. [20] emphasize the well-established effectiveness of anticoagulants in reducing the incidence of stroke and venous thromboembolism in this particular population. However, despite their proven efficacy, these medications are often unjustly under-utilized in older individuals due to concerns surrounding the risk of falls and fall-related injuries, including intracranial hemorrhage. Therefore, it is imperative to possess a comprehensive understanding of the risks and benefits associated with anticoagulant therapy in older adults, while taking into consideration their fall risk. The authors provide a thorough summary of the existing literature concerning the use of anticoagulants and the potential occurrence of fall-related adverse events in older individuals at risk of falls, who have a history of atrial fibrillation or venous thromboembolism. They demonstrate that the absolute risk of sustaining a serious fall-related injury is low and, in general, is outweighed by the reduction in stroke risk observed in cases of atrial fibrillation. Furthermore, the authors caution against off-label dose reduction of direct oral anticoagulants (DOACs), as doing so can diminish their effectiveness while having limited impact on bleeding risk.