Overactive bladder syndrome (OAB) is poorly understood and comprises several lower urinary tract symptoms. Identifying patients suffering with OAB is deceptively simple, given the broadly encompassing symptoms within the syndrome. However, a lack of a clear understanding of the pathophysiology, reliable diagnostic criteria, and targeted therapies make OAB complex to manage.

Idiopathic OAB is a diagnosis of exclusion with urgency being the central symptom, which is a subjective bladder sensation.¹ The symptomatology of OAB differs from person to person. Urgency and urgency incontinence have many phenotypes, with some patients having random urine leaking without any strong sensation, whereas others are leaking with known triggers such as running water or keys in the door, and others only in route to the toilet. Some have small volume leaks, whereas others completely flood and empty the bladder involuntarily. Urgency also has many variants, with constant urgency, urgency only when full, urgency sensed in the urethra only, post-void urgency, and many more. The only routinely used categorization of the condition is dry vs wet OAB, and it is not known if wet and dry OAB are different conditions or represent a spectrum of severity. Do these different symptoms have different etiologies?

Further complicating the diagnosis and management of OAB is that routine diagnostic testing may not reveal any abnormalities. For example, there are no pathognomonic findings on urodynamics (UDS), with a normal study being relatively common, especially among women,² and urodynamic parameters not correlating with symptom severity, scores on symptom scores, or response to medical therapy.³

The etiology and pathophysiology of OAB remain elusive, perhaps a sign there may not be one unifying explanation for OAB. Proposed pathophysiology ranges from afferent or efferent nerve dysfunction, detrusor muscle or mucosal disease, or is it the central nervous system? Occult neurological dysfunction may be an explanation, especially among those patients who respond poorly to standard therapy.⁴

It is not surprising that this population, treated like a homogeneous condition, responds to treatments in a heterogeneous way with a large variability in treatment outcome, but little to help with treatment planning except through patient-centered shared decision-making.⁵ Better phenotyping for the clear purpose of offering more tailored therapy is greatly needed.⁶ A frail patient with difficulty mobilizing, having urgency incontinence going from sitting to standing is clearly different from the younger patient with constant urgency and small volume voiding days and night. The Symptoms of the Lower Urinary Tract Research Network is focusing solely on patients with urgency in their current recruitment to the study with hopes of better phenotyping to add on to the already refined clusters⁷ of symptoms and will be focusing on many of the abovementioned symptoms.

Conservative therapies such as urge suppression, timed voiding, and fluid/bladder irritant management remain mainstays in treatment, but other than a voiding diary that reveals excess fluid intake to target,⁸ there is scarce guidance. Often overlooked, however, is that these better habits must be continued even after moving on to second- or third-line therapy. A common cause of third-line therapy failures in my clinical practice are patients going back to old habits and having worsening OAB that appears perplexing until a voiding diary and history are completed.

The clinical equipoise between pharmacological treatment options makes treatment of OAB preference sensitive,⁵ meaning many oral agents with no clear superior regimen for symptom relief with all the long-acting agents improving symptoms similarly, and therapy is more often chosen for the favorable side effect profile or cost. There has been nascent work to predict response to anticholinergics using machine learning algorithms, but these tools have not been widely adopted.⁹ Given the likely heterogeneous nature of OAB, it would seem logical to at a minimum try both an antimuscarinic and beta3-agonists given their different receptor profile. While research has not produced other viable oral therapies, clearly these are needed since current options are limited and many do not wish to proceed to advanced treatment.

It is a logical solution to progress to third-line therapies with percutaneous tibial nerve stimulation, sacral neuromodulation, or botulinum toxin when oral agents fail. Unfortunately, just as there is equipoise with pharmacotherapy, there remains no testing or clear patient factor that will guide choices of third-line therapies since there is equivocal or absent data on effectiveness between options.¹⁰ Again, barring comorbid conditions such as fecal incontinence or incomplete bladder emptying on top of OAB where neuromodulation can have dual benefits, this is a preference-sensitive decision. As such, decision-making often rests on avoidance of side effects or complications.

The biggest dilemma facing clinicians is how to proceed when third-line agents fail. It is easy to simply try whatever third-line agent that has not been tried as the next step, but data are sparse on the effectiveness of this strategy and chances of success diminish with each failed attempt.¹¹ UDS is often employed, more to rule out other pathology such as stress incontinence or poor compliance, but there are still no clear UDS findings encouraging one modality over the other.⁶ In my clinical practice, repeating UDS is best utilized to uncover other missed diagnoses such as stress incontinence or bladder outflow obstruction.

The diagnosis and management of overactive bladder syndrome are complex; research has not identified a unifying pathophysiology, nor has diagnostic testing led to reliable patterns that can guide treatment. Nascent research has focused on phenotyping OAB, identifying predictors of treatment outcomes, and improved decision-making by incorporating these into shared decision-making. Each step presents an open opportunity for additional research. One thing is certain, we should strive for up-front and clear communication with patients regarding OAB as a poorly understood and chronic syndrome, with interventions designed to mitigate symptoms, rather than to “treat or resolve” an underlying condition. This may help reinforce the multimodal symptom management strategy that may cycle through treatments throughout the life course.