The International Continence Society defines OAB as: A condition with characteristic symptoms of urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence, in the absence of urinary tract infection or other obvious pathology.²

Urgency is defined as the complaint of a sudden, compelling desire to pass urine which is difficult to defer, and urgency incontinence is the involuntary leakage of urine, associated with a sudden compelling desire to void.³

In terms of frequency, up to seven episodes during waking hours are considered normal, but this number is highly variable based on hours of sleep, fluid intake, comorbid medical conditions, and other factors.

Nocturia is defined as frequent nighttime voiding. These four factors are considered the pivotal drivers of quality of life (QoL) deterioration in patients living with OAB.^2,3

What causes OAB?

The aetiology of OAB is multifaceted, linked to age-related anatomical and tissue changes, lifestyle choices, comorbidities, and personal factors. Beyond profoundly affecting QoL, OAB exerts a broader health toll. Patients with nocturia may develop depression due to sleep disruption, elevating the risk of bone fractures and mortality – especially in elderly patients.^4,5

Urinary urgency and frequency are the two primary symptoms of OAB and are often linked to involuntary contractions of the detrusor smooth muscle, referred to as detrusor overactivity (DO). DO is the main underlying cause of OAB, affecting >60% of patients. In men,  this figure is higher, affecting ~70% of patients.⁵

Several factors contribute to the development of OAB that affect bladder smooth muscle, neuronal function, and urothelial function. Although OAB can affect children and young adults, this condition is most common in patients >40-years. Ageing is associated with increasing fibrosis of the detrusor that may contribute to the reduced bladder compliance and DO observed in patients.^2,5

Inflammation markers increase with age in OAB patients. Bladder outlet obstruction causes bladder wall changes, including hypertrophy, fibrosis, and urothelial dysfunction, with toll-like receptors implicated in inflammation.⁵

Psychological stress contributes to OAB development, with local and central changes in bladder function driven by corticotropin-releasing factors and catecholamines.⁵

Obesity and metabolic syndrome show associations with OAB, possibly due to inflammation and oxidative stress. Obesity appears to be an independent predictor for OAB.⁵

Undetected low-level bacterial infections may underlie refractory OAB, with infection increasing sensory responses to bladder filling, possibly through elevated tissue cytokines.⁵

How is OAB diagnosed?

It is important to note that there are often no visible clinical signs of OAB. A careful history and evaluation are the cornerstones of diagnosis. A detailed patient history should include assessments for conditions like recurrent urinary tract infections, bladder calculi, and bladder tumours.⁶

Furthermore, clinicians should investigate general factors and other risk factors that can contribute to OAB such as diabetes, stroke, spinal cord injuries, multiple sclerosis, pelvic surgeries, immobility, dementia, and medication use.⁶

Some medications impact the functioning of the bladder such as reducing urethral pressure or causing excess urine production. Radiotherapy for certain cancers can also irritate the bladder lining, affecting bladder functioning.⁶

The physical evaluation should include an abdominal examination for masses or distension, neurological screening for upper and lower motor lesions, rectal examination for anal sphincter tone, and vaginal examination for pelvic organ prolapse and signs of leakage.⁶

A bladder diary, detailing daily bladder habits, is a valuable initial assessment tool, helping understand voiding frequency, volume, and patterns.⁶

Laboratory tests, including urine analysis, culture, and blood tests, are recommended. Post-void residual urine can be measured using ultrasound or catheterisation, with uroflowmetry to assess urinary flow patterns.⁶

Management options

OAB management includes both non-pharmacological and pharmacological interventions. First-line interventions include non-pharmacological strategies such as patient education, lifestyle modifications (eg smoking cessation, weight reduction, dietary changes [reducing caffeine, acidic foods, and alcohol intake], bowel regulation, and exercise), bladder retraining, and pelvic floor muscle training.⁶

Bladder retraining involves regular urination intervals, increasing bladder capacity over time. Pelvic floor muscle training can reduce detrusor contractions and episodes of urgency and urge incontinence.⁶

Second-line interventions include the use of anticholinergics, which are the mainstay of pharmacological treatment in OAB. These agents inhibit cholinergic-muscarinic receptors at the neuromuscular junction, reducing parasympathetic-induced detrusor contractions. They may also act on urothelial sensory receptors, inhibiting afferent nerve activity.^3,6

Flavoxate was the first antimuscarinic agent approved (1970), followed by oxybutynin (1975), which showed superior efficacy in the management of OAB compared to flavoxate. In 1996, tolterodine was introduced as another agent in this class. In 2004, darifenacin, solifenacin, and trospium were approved.^6,7

Despite their efficacy, anticholinergics are associated with bothersome side effects, leading to treatment discontinuation. Commonly reported side effects of antimuscarinics include dry mouth, constipation, blurred vision, gastro-oesophageal reflux, and cognitive impairment.⁷

Superior side effect profile of newer antimuscarinics

New antimuscarinics such as solifenacin are associated with a more favourable side effect profile compared to older medications. Furthermore, less frequent dosing is required.⁷

Solifenacin is a bladder-selective antimuscarinic. Administered orally, solifenacin exhibits bladder tissue selectivity over salivary glands and is ~12 times more selective for muscarinic subtype M3 receptors. Of the five known muscarinic subtypes (M1 through M5), the M3 receptors subtype appears to be the most clinically relevant in the human bladder. M3 receptors are also involved in contraction of the gastrointestinal smooth muscle, saliva production, and iris sphincter function.^7,8

The safety and efficacy of solifenacin have been established in four 12-week randomised, double-blind, placebo-controlled studies in more than 3000 patients with symptoms of urinary frequency and urgency and/or urge/mixed incontinence that had persisted for at least three months.⁷

In these studies, solifenacin 5mg to 10mg daily was more effective than placebo in reducing the number of micturitions and urge incontinence episodes per 24 hours and increasing the volume of urine voided per micturition. Solifenacin effectively reduced urgency, incontinence episodes, urinary frequency, and increased voided volume.⁷

In head-to-head trials, solifenacin demonstrated superior efficacy in reducing urgency, incontinence, and pads used, with a favourable safety profile compared to other antimuscarinics.⁸

A 2012 Cochrane review compared various anticholinergics for the treatment of  OAB in adults. The review included 86 trials (=31 249). Key findings showed that tolterodine had fewer withdrawals due to side effects and less risk of dry mouth compared to oxybutynin. Solifenacin demonstrated better efficacy and less dry mouth risk compared to tolterodine.⁹

More recently, Nazir et al compared the efficacy and tolerability of solifenacin 5mg/day versus other oral antimuscarinics for the treatment of OAB. Their meta-analysis included 53 trials. They report that solifenacin 5mg/day was significantly more effective than tolterodine 4mg/day for reducing incontinence and urgency urinary incontinence episodes, but significantly less effective than solifenacin 10mg/day for micturition.¹⁰

Solifenacin 5mg/day had a statistically significant lower risk of dry mouth compared with darifenacin 15mg/day, fesoterodine 8mg/day, oxybutynin extended-release 10mg/day, oxybutynin immediate-release 9mg-15mg/day, tolterodine immediate release 4mg/day, propiverine 20mg/day, and solifenacin 10mg/day.¹⁰

There were no significant differences between solifenacin 5mg/day and other antimuscarinics for risk of blurred vision, or for 11 of 17 active comparators for risk of constipation.¹⁰

OAB prescribing considerations

Patients with OAB generally have a greater number of comorbid medical conditions and have a higher prevalence of polypharmacy compared to patients without OAB. Drug-drug interactions (DDIs) are therefore a major concern.¹¹

When prescribing anticholinergics for OAB, caution is advised, especially in frail elderly patients and when combined with other medications with anticholinergic effects. The concurrent use of anticholinergics and drugs metabolised by CYP2D6 can lead to DDIs and result in unknown cumulative effects.¹¹

Patients should undergo medication reviews regularly, and clinicians should consider substituting or discontinuing certain agents when necessary. Clinicians should also monitor medication adherence, particularly when dose adjustments may result in DDIs.¹¹

How do you manage treatment-resistant OAB?

When anticholinergics fail, minimally invasive options include botulinum toxin injections into the detrusor muscle, neuromodulation (posterior tibial nerve or sacral neuromodulation), and β-adrenergic therapies.⁶

Botulinum toxin injections temporarily block acetylcholine release, reducing detrusor contractility. Neuromodulation uses electrical signals to regulate bladder and pelvic floor function, while augmentation enterocystoplasty increases bladder size, but it is associated with complications.⁸

Conclusion

OAB affects a substantial portion of the global population, particularly among the elderly. Understanding its multifaceted aetiology, the impact on QoL, and the available management options is crucial. While anticholinergics, with newer agents like solifenacin showing promise, remain a cornerstone of treatment, the consideration of comorbidities, potential DDIs, and the management of treatment-resistant OAB are vital aspects of patient care. Minimally invasive interventions may offer alternatives when conventional treatments prove ineffective. Overall, a comprehensive approach is necessary to address the complex nature of OAB and improve the well-being of affected individuals.

References

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2. Haylen BT, de Ridder D, Freeman RM, et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn, 2010.
3. Lightner DJ, Gomelsky A, Souter L, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU Guideline amendment 2019. J Urol, 2019.
4. Edmondson SD. CNS, Pain, Metabolic Syndrome, Cardiovascular, Tissue Fibrosis and Urinary Incontinence. Comprehensive Medicinal Chemistry III, 2017.
5. Chess-Williams R, Sellers DJ. Pathophysiological Mechanisms Involved in Overactive Bladder/Detrusor Overactivity. Curr Bladder Dysfunct Rep, 2023.
6. Leron E, Weintraub AY, Mastrolia SA, Schwarzman P. Overactive Bladder Syndrome: Evaluation and Management. Curr Urol. 2018
7. Hesch K. Agents for treatment of overactive bladder: a therapeutic class review. Proc (Bayl Univ Med Cent), 2007.
8. Hashim H, Abrams P. Treatment options for overactive bladder syndrome. Therapy, 2005.
9. Madhuvrata P, Cody JD, Ellis G, et al. Which anticholinergic drug for overactive bladder symptoms in adults. Cochrane Database Syst Rev, 2012.
10. Nazir J, Kellerher C, Aballea S, et al. Comparative efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents in overactive bladder: A systematic literature review and network meta-analysis. Neurourol Urodyn,
11. Rutman MP, Horn JR, Newman DK, et al.Overactive Bladder Prescribing Considerations: The Role of Polypharmacy, Anticholinergic Burden, and CYP2D6 Drug-Drug Interactions.Clin Drug Investig, 2021.