Preventing the 17-Year Gap in Overactive Bladder Prescribing Practices: The Need for Implementation Science

A recent JAMA news article highlighted the pervasive chasm between available evidence and routine clinical practice.¹ It discussed sobering evidence that it takes an average of 17 years for an evidence-based intervention to be implemented in routine clinical practice, and only 1 in 5 interventions is implemented at all.^1,2 The article went on to describe success stories from the burgeoning field of implementation science, a field of study that focuses on developing interventions to promote the adoption of evidence-based clinical practices with the goal of closing the 17-year gap.³

As a urologist, I was struck by the relevance of this article to the treatment of overactive bladder (OAB). OAB is a chronic condition, especially common in older adults, that can profoundly impact quality of life leading to increased incidence of depression, anxiety, social withdrawal, and falls.⁴ AUA guidelines for OAB recommend pharmacologic treatment with anticholinergics or β₃-adrenergic receptor agonists as second-line treatment or as first-line treatment in combination with behavioral therapy.⁴ Although anticholinergics may be effective for some patients, reports of a potential association between oxybutynin and cognitive dysfunction, including impaired memory, began emerging 25 years ago⁵ and were reviewed as early as 2005.⁶

As an aging baby boomer, I am becoming increasingly worried about reducing and preventing cognitive decline in myself, my friends, and my family. Over the last 5 years, multiple observational studies have found an association between the use of OAB anticholinergics and dementia risk. According to a comprehensive nested case-control study involving 58,769 patients with dementia and 225,574 matched controls, there were significant statistical associations between dementia risk and exposure to anticholinergic antidepressants, antiparkinson drugs, antipsychotics, bladder antimuscarinics, and antiepileptics.⁷ The results remained significant even after accounting for confounding variables. Furthermore, a retrospective population-based matched cohort study using the Ontario Drug Benefit database found an increased risk of incident dementia among 47,324 patients with OAB who initiated an anticholinergic relative to 23,662 patients with OAB who initiated treatment with a β₃-adrenergic receptor agonist (hazard ratio, 1.23; 95% CI, 1.12‒1.35).⁸ Because both cohorts of patients had symptoms of OAB, these results suggest that the increased incidence of dementia in the anticholinergic cohort is not simply a product of patients being treated for dementia-related incontinence prior to being diagnosed with dementia.

In light of the growing evidence that OAB anticholinergics are associated with cognitive risks, a recent white paper from the Society of Urodynamics, Female Pelvic Medicine, and Urogenital Reconstruction (SUFU) recommended that the decision to use anticholinergics to treat OAB for ≥ 3 months should include shared decision-making between the clinician and patient, which weighs the potential benefits of anticholinergic therapy against the increased risk of dementia.⁹ The SUFU white paper emphasizes that cognitive risks should be considered regardless of patient age, as the risk of incident dementia may be both delayed and cumulative. The white paper also recommends considering third-line treatments earlier for appropriate patients and that, when pharmacotherapy is indicated, a β₃-adrenergic receptor agonist should be considered before an anticholinergic. Furthermore, the 2023 American Geriatrics Society Beers Criteria recommend reducing or avoiding unnecessary anticholinergics, including all urinary antimuscarinics, in older adults due to risks including cognitive decline, delirium, and falls or fractures, all of which increase if patients receive multiple anticholinergic medications.¹⁰

Implementation science is urgently needed to ensure that clinical practice in OAB treatment does not fall into the 17-year gap. Available evidence indicates that anticholinergic use is pervasive, constituting ∼80% of Medicare claims for OAB medications in patients aged ≥ 65 years in 2017.¹¹ However, these data predate the publication of large observational studies that demonstrated an association between anticholinergic use and incident dementia, as well as the most recent guidance from SUFU and the American Geriatrics Society. There is an urgent need for up-to-date and comprehensive studies to assess whether anticholinergic prescribing practices are changing in response to the clinical evidence. In addition, practical resources are needed to guide patient-provider discussions of the cognitive risks associated with anticholinergic medications, as recommended by the SUFU white paper. Studies assessing patient and provider awareness of the risks associated with anticholinergic medications for OAB may help identify knowledge gaps. Interventions can then be developed to help ensure that all patients who may receive OAB anticholinergics are aware of the potential cognitive risks and alternative treatment options.

I recognize that anticholinergics are often used for economic reasons, such as insurance requirements to trial anticholinergics before approving newer therapies.¹² The time and administrative burden of securing prior authorizations for newer therapies may be a barrier to reducing anticholinergic use. The step-therapy process may also lead to miscommunications that result in patients discontinuing OAB treatment or remaining on an anticholinergic for much longer than originally intended.

Implementation studies could evaluate the real-world outcomes of step therapy and identify patients who may be at risk of discontinuing treatment or remaining on a therapy that is no longer a good fit due to changes in their individual medical history and risk factors. This could give providers much needed tools to better manage the step-therapy process and find ways to de-escalate anticholinergics where appropriate. In addition, real-world evidence quantifying the costs associated with elevated dementia risk in patients receiving anticholinergic medications may encourage payors to improve access to alternative treatments. I would also encourage physicians and medical societies to continue advocating for public policy changes, such as the Safe Step Act, that would curtail the use of step-therapy protocols to limit patients’ access to medically appropriate treatments.

Some potential barriers to de-escalation of anticholinergic medications were brought to light by a recent study that examined factors associated with implementation of pharmacist-led recommendations to de-escalate anticholinergics in the PACE (Programs of All-Inclusive Care for the Elderly).¹³ PACE includes medically complex older adults who are likely at particularly high risk of experiencing cognitive effects or falls/fractures related to anticholinergic medications. The authors noted that patients often resist efforts to de-escalate anticholinergic medications due to the substantial impact of OAB symptoms on their quality of life, suggesting that patients may be more likely to de-escalate anticholinergics if they can switch to an effective nonanticholinergic OAB treatment. Furthermore, the study found that patient characteristics—including taking < 10 chronic medications, receiving higher daily doses of urinary anticholinergics, and baseline calcium channel blocker use (which may cause incontinence)—were predictors of implementing recommendations to de-escalate anticholinergics. Surprisingly, the study also found that de-escalation was less likely to be implemented if recommendations included multiple options. This suggests that patients may remain on anticholinergics because health care providers across primary and specialty care may be overwhelmed by coordination and implementation of complex recommendations. Developing interventions to de-escalate anticholinergic medications while minimizing cognitive load on prescribers may help with implementation of evidence-based treatment guidelines in OAB. More data may also be useful to understand the factors driving patient preferences for OAB treatment strategies, so that patients can be effectively counseled on appropriate alternatives to anticholinergic medications.

I believe there is an immediate need for implementation science to bridge the gap between evidence and prescribing practices to ensure that OAB treatment is evidence based. In the meantime, I call on providers to examine your own practices and develop an implementation plan to ensure appropriate treatment approaches for patients with OAB, particularly older adults. This could include setting aside time to counsel patients on potential cognitive risks when initiating or renewing a prescription for an anticholinergic, identifying barriers to avoiding or de-escalating anticholinergics along with strategies to overcome them, and regular monitoring to evaluate the effectiveness of the implementation plan and adjust as needed. Our patients cannot wait 17 years.