Overactive bladder syndrome: risk factors, diagnosis, management and medicine optimisation in older people

Introduction

Overactive bladder syndrome (OAB) is characterised by the increased frequency of the urge to urinate during the day or night, with or without urinary incontinence, in the absence of urinary tract infection (UTI) or other detectable medical conditions​[1,2]​.

OAB is a common condition that affects a substantial portion of the population​[3]​. It is estimated to affect approximately 16.6% of the European population aged 40 years and above and its occurrence increases with age​[4–6]​. The rise in prevalence with age can be attributed to increased rates of idiopathic detrusor activity, comorbidities, limited mobility and polypharmacy​[7]​.

In the UK, the direct economic impact of OAB on the NHS is estimated to exceed £1bn annually​[8,9]​. A study estimated the economic cost of OAB in the United States at approximately US$26bn annually, equating to US$267 per person per year (comparable with gynaecological and breast cancer)​[10]​.

The symptoms of OAB extend beyond the physical discomfort of frequent urination and urinary incontinence. OAB has adverse effects on multiple aspects of patients’ lives, including daily activities, sleep patterns, mental wellbeing and quality of life​[11–13]​. Moreover, individuals with OAB are also more likely to experience comorbidities, such as UTIs and skin infections, and have an increased risk of falls​[14–16]​.

In a study of adults with OAB, 54% of patients reported being bothered by their symptoms. The study used two validated measures, ‘Patient Perception of Bladder Condition’ and ‘Overactive Bladder-Validated 8′, to define symptom bother in OAB cases. Similar rates were observed among both men and women, and it was found to have a significant impact on patients’ quality of life​[17]​.

A population-based UK study of 1,415 women reported prevalence of urinary incontinence at 39.9%​[7]​. While women tend to report incontinence more frequently than men, the occurrence becomes comparable in both sexes after the age of 80 years. Age is a significant factor in the development of urinary incontinence and it affects both men and women alike​[5,6]​.

Studies have shown that urinary incontinence is associated with a higher risk of mortality, particularly among older adults. A large meta-analysis investigating the relationship between urinary incontinence and mortality identified that patients with urinary incontinence have a 27% increased likelihood of mortality​[18]​. Furthermore, urinary incontinence is a prevalent risk factor for pressure ulcers, as it can cause skin damage, increasing susceptibility to pressure ulcers​[19]​. A study of older adults in care homes revealed a 24% increased risk of all-cause mortality associated with urinary incontinence​[20]​. However, it is unclear if urinary incontinence directly causes mortality or serves as an indicator of overall poor health​[18]​. Further research is needed to interpret the complex relationship between urinary incontinence and mortality, including potential underlying mechanisms and contributing factors.

Pharmacists can help patients with OAB by educating them on the different treatment options available, providing lifestyle advice to improve symptoms and identifying opportunities to optimise their use of medicines. 

Pathophysiology

OAB syndrome is characterised by non-specific storage issues with poorly defined pathophysiology​[21]​. The symptoms arise from involuntary contractions of the detrusor muscle during the filling phase of the micturition cycle, suggesting a potential impact on the sensory mechanisms of the bladder​[22]​. This leads to a sense of urgency to empty the bladder at smaller quantities than normal conditions would require. The detrusor muscle is strongly innervated, and the proper functioning of the bladder involves a complex mechanism between the central and peripheral nervous systems​[22]​. The motor component of the bladder, coordinated by the parasympathetic nervous system, regulates the intensity of detrusor contractions​[22,23]​. The sympathetic component, which originates from the hypogastric nerve and acts on beta receptors, is responsible for relaxing the detrusor​[21]​.

Detrusor overactivity is primarily mediated by acetylcholine-induced stimulation of muscarinic receptors in the bladder, which includes M2 and M3 receptors​[22,23]​. Acetylcholine released from parasympathetic nerves stimulates M3 receptors responsible for bladder contraction. This contraction is a result of an increase in cytosolic calcium from intracellular stores. Activation of M2 receptors causes a decrease in cyclic adenosine monophosphate (cAMP), thereby preventing relaxation. Unstable bladders exhibit altered responses to stimuli and often show enhanced spontaneous contractile activity in smooth muscles. Specific patterns exhibited in tissues from unstable bladders vary subtly depending on the underlying aetiology. For instance, obstructed bladders demonstrate hypersensitivity to cholinergic agonists acting at muscarinic (M2 or M3) receptors, while denervated bladders show increased M3 receptor expression​[24]​.

The main pharmacological treatment for OAB currently revolves around the use of muscarinic antagonists​[25]​. These drugs block muscarinic receptors at the neuromuscular junction, effectively preventing acetylcholine-mediated bladder contractions​[22]​.

Despite extensive research, the exact cause of detrusor overactivity remains unknown​[26]​. However, three main factors have been proposed as potential contributors to OAB: myogenic, neurogenic and urotheliogenic factors​[26–28]​.

The myogenic factor theory suggests that damaged intrinsic neurons in the bladder wall, along with secondary changes in smooth-muscle properties over time, may increase excitability and electrical coupling between cells. Consequently, a local contraction occurring in any part of the detrusor can propagate throughout the bladder wall, leading to coordinated myogenic contraction of the entire bladder. Additionally, partial loss of nerve supply of the detrusor can lead to smooth-muscle cells becoming hyper-excitable when responding to stimulation​[22,26–29]​.

In the neurogenic factor theory, damage to central inhibitory pathways in the brain and spinal cord results in a loss of inhibitory effects and unmasks the early voiding reflexes that trigger detrusor overactivity. Neurogenic causes may be observed in patients who have experienced cerebrovascular events, multiple sclerosis or Parkinson’s disease, because these conditions can lead to nerve damage​[26,28,30]​.

The urotheliogenic factor theory focuses on the role of the urothelium, which was previously considered mainly as a barrier but is now recognised as a responsive structure, capable of detecting thermal, mechanical and chemical stimuli. Transmitters released from the urothelium can alter the excitability of afferent nerves and affect detrusor muscle contractility. Animal studies suggest the absence of the urothelium can result in an increased spontaneous activity of the detrusor, while chronic urothelial injury is linked to increased urinary frequency and reduced voiding volume​[26,27,31]​.

Risk factors

There is a tendency to label OAB as idiopathic owing to its poorly understood pathophysiology; however, it is crucial to view OAB as a complex condition that can originate from a variety of pathophysiological mechanisms. Identifying the underlying causes on an individual basis could significantly enhance our ability to manage the condition and offer personalised care​[27]​.

There is a significant correlation between OAB and both age and obesity​[32]​. Additionally, various neurological conditions, such as dementia, diabetic neuropathy, multiple sclerosis, Parkinson’s disease, stroke or damage to pelvic and spinal nerves increase the risk of OAB​[25,28,30,33]​. Conditions such as UTIs, sexually transmitted infections, bladder stones, and bladder cancer might also amplify the likelihood of OAB development​[30,33,34]​.

While women with pelvic organ prolapse tend to experience a higher prevalence of OAB symptoms, a direct correlation between prolapse stage and OAB symptoms has not been established​[35]​. The postmenopausal stage has also been linked to an increase in OAB symptoms. This connection can be attributed to the decline in oestrogen levels and its role in modulating lower urinary tract function​[21,25]​.

For men, conditions such as benign prostatic hyperplasia, prostatitis, and prostate cancer are associated with OAB symptoms​[33]​.

It is worth noting that medications can exacerbate or trigger OAB as a side effect. For instance, diuretics can worsen OAB by promoting excessive urine production, while hormone replacement therapy, antidepressants, antipsychotics and alpha-adrenergic antagonists may induce involuntary detrusor contractions​[30,34,36]​. Simultaneously, lifestyle and behavioural factors also contribute to OAB, with smoking, excessive coffee consumption and alcohol intake identified as significant​[13,21,33,34,37]​.

Early identification of modifiable risk factors could guide effective OAB management strategies and pharmacists play a pivotal role in offering advice on lifestyle adjustments and medicines optimisation​[25,30]​.

Diagnosis

The diagnosis of OAB involves an evaluation of patients’ signs and symptoms while ruling out other conditions. A comprehensive approach, including medical history, physical examination and laboratory tests is required for an accurate diagnosis of OAB.

A detailed history should be taken, including the patient’s baseline urinary function and the duration of their current symptoms​[33,34,38–41]​. Additionally, an assessment of bladder storage capacity and voiding ease is also needed​[33]​. Inquiring about the patient’s daily fluid intake patterns and identifying potential bladder irritants creates an opportunity to educate them about modifiable behaviours. Keeping a bladder diary provides an objective measure of daily fluid intake, detailing the types and amounts of fluids consumed, as well as voiding habits. The bladder diary should be completed for a minimum of three days to differentiate between urinary frequency, polyuria, nocturia and nocturnal polyuria​[34,38,39]​.

A physical examination should cover weight, gait abnormalities and potential neurological indicators. Palpation of the abdomen can be performed to rule out a distended bladder or mass. For women, a pelvic examination is necessary to identify potential causes of urinary incontinence, such as pelvic organ prolapse, urethral diverticulum, pelvic masses and atrophic vaginitis​[6,34,40]​. For men, a digital rectal examination can be performed to evaluate the prostate for size, texture, nodules and tenderness​[33,40]​. In addition, external genitalia should be examined to identify conditions contributing to or causing OAB; for example, phimosis, meatal stenosis or penile cancer​[33,41]​.

A medication review should also be performed. Assessment of comorbidities, such as sleep apnoea, diabetes and heart failure are important, because these factors can contribute to OAB symptoms​[34,39]​. 

Laboratory testing should include urinalysis to exclude infections and haematuria. Urine dipstick testing for blood, glucose, protein, leukocytes and nitrites is recommended. If a patient exhibits UTI symptoms and dipstick analysis shows positive results for leukocytes and nitrites, a mid-stream urine sample should be sent for culture and sensitivities, with antibiotics prescribed while awaiting culture results​[6,33,34]​.

However, for individuals aged 65 years and above, including both men and women, urine dipsticks should not be used for diagnosing UTIs. Dipsticks become unreliable with increasing patient age. Up to half of older adults and the majority of those with a urinary catheter may exhibit asymptomatic bacteriuria, leading to a positive urine dipstick result. This prohibition also applies to individuals experiencing recurrent UTIs or situations where there is potential for bacterial resistance. In such cases, a mid-stream urine test should be conducted for accurate diagnosis. It is important to note that asymptomatic bacteriuria is not harmful and does not necessitate treatment​[42,43]​.

Serum creatinine and estimated glomerular filtration rate (eGFR) should be measured and calculated if clinically indicated​[33,41]​. The need for prostate-specific antigen (PSA) testing in men should also be considered​[33]​.

A diagnosis of OAB does not require urodynamic confirmation of detrusor overactivity, since normal urodynamics do not exclude OAB. Urodynamic tests may only be conducted by specialists in cases of refractory OAB to determine whether another cause is contributing to the symptoms​[3,6,40,44]​.

When a patient presenting with symptoms of OAB is identified in community pharmacy, the pharmacist should refer the patient to the GP for further testing and diagnosis. Non-pharmaceutical management and lifestyle advice can be provided to help in managing the symptoms and the condition (as detailed in the management section below). If any of the following red-flag symptoms are identified, the patient should be referred to secondary care, with clinical judgement determining the urgency of the referral.

Management

In the management of OAB, the focus should be on identifying and addressing the underlying causes, although it is important to note that a specific cause is often not easily identified​[33,34]​.

Bladder training should be offered as the first-line treatment, with a minimum duration of six weeks. This technique involves the deliberate delay of urination following the initial urge, achieved through various methods, such as crossing the legs or engaging in pelvic floor exercises. The goal in the beginning is to extend the time before urination by 5–15 minutes, gradually increasing this interval over time. This practice effectively teaches the bladder to hold more urine and helps to reduce the number of times needed to pass urine, leading to a gradual alleviation of symptoms​[45]​.

To further enhance management, adjustments to lifestyle are advised. These include reducing the consumption of bladder-irritating substances, such as caffeine and alcohol. Additionally, tailored guidance on physical activity and diet is recommended for overweight patients, and consideration for smoking cessation if applicable​[13,21,33,34,37,46]​.

It is also essential to strike a balance when it comes to fluid intake. Both inadequate and excessive fluid intake can lead to OAB symptoms. Fluid intake should not be limited as this could result in complications such as UTIs and bladder irritation​[33,34]​.

The use of containment products, including absorbent items, hand-held urinal bottles and toileting aids, can enhance comfort and security for patients with urinary incontinence. These products could help patients in facilitating day-to-day activities and improve their quality of life; however, it is important to acknowledge that these solutions are not sustainable in the long term owing to associated costs and potential impact on dignity​[33,34]​.

In cases where symptoms persist after initial management, the use of antimuscarinic drugs, such as the medication listed in the Table can be considered​[47,48]​. It is essential to educate patients about the gradual onset of these drugs’ effects, which may take a minimum of four weeks, and the possibility of experiencing adverse effects. Open discussion about the probability of treatment success is also important for managing patient expectations​[33,34]​.

Throughout the treatment journey, regular reviews play a critical role. Patients should be assessed every 4 to 6 weeks until symptoms are stable, then every 6 to 12 months. More frequent reviews are recommended for patients aged over 75 years. These reviews should encompass a comprehensive assessment of symptoms, the impact on quality of life, potential adverse effects and the ongoing suitability of the chosen treatment​[33,34]​.

In cases where antimuscarinic drugs are unsuitable, not tolerated or ineffective, mirabegron can be offered as an alternative treatment​[47]​.

If all treatments prove ineffective, the patient should be referred to a specialist urologist for thorough assessment and management. Secondary care options could include interventions, such as botulinum toxin injections into the bladder wall, percutaneous sacral nerve stimulation, augmentation cystoplasty and urinary diversion​[33,34]​.

For post-menopausal women with vaginal atrophy, intravaginal oestrogen therapy should be considered​[34]​.

Lastly, it is important to ensure individuals have access to information and support resources. Bladder and Bowel Community offers a variety of resources on their website, including a discreet ‘Just can’t wait’ toilet card, which can prove invaluable in urgent situations. Moreover, the NHS also provides online resources for those dealing with urinary incontinence. These resources offer comprehensive support and guidance to individuals seeking effective management strategies for their condition​[33,34]​.

Adverse effects of anticholinergic medications

Anticholinergic medications carry a significant adverse effect profile​[49,50]​. Common adverse effects include dry mouth, urinary retention and constipation​[51]​. The impact of these adverse effects is especially concerning among older adults owing to age-related changes in pharmacokinetic and pharmacodynamic processes, coupled with the presence of comorbidities and polypharmacy​[52]​. Even medications with individually low anticholinergic activity can collectively contribute to a significant overall anticholinergic effect when used concurrently​[53]​. 

This accumulation of anticholinergic burden (ACB) is closely linked with severe outcomes, including falls and mortality​[54]​. The Public Health Outcomes Framework reported that, in 2021/2022, there were approximately 223,101 emergency hospital admissions related to falls among patients aged 65 years and older. Of these admissions, approximately 146,964 (65.9%) involved patients aged 80 years and older. The total annual cost of fragility fractures to the UK in 2022 has been estimated at £4.4bn, including £1.1bn for social care. Hip fractures alone account for around £2.0bn of this total. The short- and long-term outlooks for patients are generally poor following a hip fracture, with an increased one-year mortality rate of between 18% and 33%​[55,56]​.

The potential for cognitive side effects arises when a drug penetrates the blood–brain barrier, influencing the central nervous system to induce drowsiness, confusion and impairments in learning and memory​[57,58]​. A comprehensive review has established a strong connection between increased anticholinergic load, cognitive decline and potential declines in physical functioning​[54]​. Furthermore, urinary anticholinergics were found to be significantly associated with an increased risk of future dementia​[59]​.

Urinary anticholinergics can be categorised as tertiary or quaternary amines​[51]​. Tertiary amines possess greater lipid solubility, a neutral charge, and a smaller molecular size. This configuration facilitates their absorption within the digestive system, and their ability to pass through the blood–brain barrier, influencing the central nervous system. By contrast, quaternary amines exhibit greater hydrophilicity and carry a positive charge, which theoretically reduces their likelihood of crossing the blood–brain barrier​[57]​. Most urinary anticholinergics for OAB fall within the tertiary amine category, except for trospium chloride, which is a quaternary amine​[60]​. In older adults, the blood–brain barrier is more permeable, and their reduced renal and hepatic drug metabolism further enhances the anticholinergic effects of these agents​[61]​. If a drug manages to breach the blood–brain barrier, permeability-glycoprotein (P-gp) could interact with its substrates and lead to active removal of the drug from the brain​[62]​. Trospium chloride is both a quaternary amine and a P-gp substrate, suggesting that it is less likely to cross the blood–brain barrier and trigger cognitive side effects when compared to other urinary anticholinergics​[49,60]​. 

For healthcare professionals and pharmacists, a priority should be reducing ACB to lessen the risk of physical and cognitive impairments in older people​[63]​. This involves minimising the use of medicines linked with elevated ACB and exploring alternative treatment strategies when feasible​[64]​. The dementia guidelines from the National Institute for Health and Care Excellence (NICE) recommend practitioners consider ACB as a potential contributor to cognitive decline and the use of validated scales to assess ACB[65]. While several validated tools exist, there is no current evidence that any one is superior to the others​[65]​.

Mirabegron

Mirabegron functions as a beta-3 adrenoceptor agonist and is licensed for the treatment of OAB. Beta-3 adrenoceptors are situated within the bladder detrusor smooth muscle; their activation triggers the relaxation of the bladder muscle, resulting in an enhanced bladder capacity​[47]​. This medication is an alternative to urinary anticholinergics and does not have the side effects frequently linked to that class of medication. 

NICE recommends mirabegron as an option for treating OAB in people for whom antimuscarinic drugs are contraindicated, clinically ineffective or have unacceptable side effects​[66]​. It also presents the cost effectiveness of mirabegron usage, reporting a range of incremental cost-effectiveness ratios (ICERs) for mirabegron compared with different antimuscarinics. NICE determined that the clinical effectiveness of mirabegron is comparable to antimuscarinic drugs, while exhibiting a different side effect profile. However, the differences in costs and effects between drugs are small and it is therefore difficult to make a reliable estimate of the ICER. Following consideration of the treatment pathway and hearing from clinical specialists, the committee concluded that it was reasonable to formulate the recommendations as they have done. 

Medicines optimisation in older people

It is well established that age correlates with OAB, with older individuals also being more prone to experiencing the anticholinergic effects of OAB treatment​[52]​. Clinical pharmacists play a pivotal role in proactively managing polypharmacy and facilitating medicines optimisation​[64]​. Pharmacists can significantly affect patient care and health outcomes in older people by providing patient education and lifestyle advice, and optimising the use of medicines​[67]​.

The National Overprescribing Review has underscored the clinical and financial consequences of overprescribing, revealing that 10% of prescription items dispensed in England are inappropriate for patients’ circumstances and preferences​[68]​. This review recommended exploring non-pharmacological alternatives to prescribing, while also advocating for the integration of deprescribing into the prescribing process, with the aim of reducing medicines wastage. 

One useful approach to balance the potential risks and benefits of pharmaceutical treatment is to assess the ‘number needed to treat’ for beneficial effects and the ‘number needed to harm’ for potential side effects. These numerical values clearly describe how many patients need to be treated for one person to experience a beneficial outcome or, conversely, for one person to experience a harmful side effect. To make this information more accessible and user-friendly, healthcare providers can present these numbers in a way that patients can easily grasp. Visual aids, such as the Cates Plot, can be particularly helpful. This diagram simplifies complex data, allowing patients to easily visualise and comprehend the potential risks and benefits associated with medication. Healthcare professionals can employ their communication skills to explore patient’s values, preferences and concerns. Understanding these aspects allows providers to tailor treatment options that align with the individual patient’s priorities.

Shared decision-making is an integral component of the comprehensive model of personalised care. It promotes a collaborative process between clinicians and patients. This collaborative approach empowers individuals to make choices that align with their personal needs and values. It also represents a journey where clinicians provide treatment options with the consideration of risks and benefits, while respecting the patient’s preferences, personal circumstances, goals and values​[68]​.

To effectively address the challenge of polypharmacy, adopting a patient-centred approach is essential during medication reviews​[69]​. This approach can enhance patient outcomes, aligning with the NHS Long-Term Plan’s focus on personalised care​[70]​. An example of this can be found in hospital settings, where patients are often initiated on catheters. Individuals with catheters may not necessarily require antimuscarinics to alleviate urinary frequency; however, it is essential to investigate whether the patient is experiencing any degree of bladder spasm. In certain instances, catheters are linked to bladder spasms, and antimuscarinics may play a role in managing the associated symptoms​[71,72]​.