Category:Overactive bladder medications

An overactive bladder medication is a medicine used to treat the symptom complex of urinary urgency, frequency, nocturia, and (in approximately one-third of cases) urge incontinence that characterises overactive bladder syndrome. The condition is now understood as a clinical-symptom diagnosis rather than a urodynamic one, and the category includes medicines that act on the detrusor muscle of the bladder wall and on its neural input: the antimuscarinic agents that block the M3-mediated detrusor contraction, the beta-3 adrenergic agonists that promote detrusor relaxation, and, for refractory cases, onabotulinumtoxinA injected directly into the detrusor.

The clinical understanding of the syndrome has evolved substantially. The term "overactive bladder" was introduced by the International Continence Society in 2002 to displace the older "detrusor instability" or "detrusor hyperreflexia" terminology, recognising that the symptoms could be diagnosed clinically without urodynamic confirmation and that medicines could be initiated on the basis of symptom assessment alone.^[1] The pharmacological landscape has been transformed by this redefinition, which made overactive bladder a treatable outpatient diagnosis for the substantial fraction (approximately one in six adults) of the developed-world population with relevant symptoms.

The first effective pharmacological treatment was the non-selective antimuscarinic oxybutynin, introduced by Marion Laboratories in 1975 on the rationale that the detrusor contraction was driven by parasympathetic acetylcholine acting on muscarinic receptors. Oxybutynin was effective but produced the full antimuscarinic toxidrome (dry mouth, blurred vision, constipation, somnolence, confusion in the elderly) at clinically useful doses; the immediate-release formulation has been progressively replaced by the extended-release tablet (1998), the transdermal patch (2003), and the topical gel (2009), each of which reduces peak concentrations and the corresponding dose-limiting adverse effects.

The next generation of antimuscarinics aimed for greater selectivity for the M3 receptor predominant on the detrusor, with less M1 affinity (the M1 receptor of the central nervous system and of the salivary acini accounts for much of the dry mouth and cognitive toxicity). Tolterodine (Pharmacia, 1998), solifenacin (Yamanouchi, 2004), darifenacin (Pfizer, 2004, the most M3-selective of the class), fesoterodine (Pfizer, 2008, hydrolysed in vivo to the active metabolite of tolterodine), and trospium (a quaternary amine that does not cross the blood-brain barrier and so produces less central toxicity) extended the class. Comparative meta-analyses show similar efficacy across the antimuscarinic class, with the differences principally in side-effect profile rather than in symptom reduction.

The transformative agent in the 2010s was the first beta-3 adrenergic agonist. Detrusor smooth muscle, although under predominant parasympathetic stimulatory control through M3 receptors, also expresses beta-3 adrenoceptors whose activation produces relaxation; the receptor was poorly accessible to traditional adrenergic medicines because beta-3 selectivity is difficult to achieve. Mirabegron (Astellas, 2012) was the first orally bioavailable selective beta-3 agonist; it reduced urge incontinence episodes and micturition frequency comparable to the antimuscarinics, without dry mouth or cognitive effect, although with a small but real signal of hypertension that has required blood-pressure monitoring on treatment.^[2] Vibegron (Urovant, 2020) followed with a similar efficacy profile and a smaller blood-pressure signal. The combination of a beta-3 agonist with an M3 antimuscarinic is now standard for symptoms not controlled on monotherapy, with the additive efficacy of two mechanisms and largely non-overlapping side-effect profiles.

For refractory cases, intradetrusor injection of onabotulinumtoxinA (Botox), administered cystoscopically at 100 to 200 units divided across 20 to 30 detrusor sites, provides 6 to 9 months of symptomatic relief by chemical denervation of detrusor muscle, at the cost of incomplete bladder emptying (and rarely the need for clean intermittent catheterisation) in approximately 5 percent of patients. Posterior tibial nerve stimulation and sacral neuromodulation are device-based alternatives. The selective M3 antagonists, the beta-3 agonists, and the chemodenervation therapies have together made overactive bladder a substantially treatable condition, and the older recommendation to "live with it" in middle age has retreated.

By mechanism:

• Antimuscarinics (cross-indexed under antimuscarinics):
  • Non-selective (older, less expensive, more side effects): oxybutynin (oral immediate- and extended-release, transdermal patch, topical gel)
  • M3-selective (modern, fewer central effects): solifenacin, tolterodine, darifenacin, fesoterodine
  • Quaternary amines (do not cross blood-brain barrier): trospium
• Beta-3 adrenergic agonists: mirabegron, vibegron
• Chemodenervation: onabotulinumtoxinA (intradetrusor injection)
• Tricyclic antidepressants (off-label, principally for nocturnal enuresis): imipramine (largely retired for this indication in favour of better-tolerated alternatives but still used in selected cases)
• Topical estrogen (for the urgency component in postmenopausal women with genitourinary syndrome of menopause): vaginal estradiol, vaginal estriol, conjugated estrogen cream

The boundary of this category is "medicine used to treat the symptoms of overactive bladder." Medicines used in stress urinary incontinence (the duloxetine approved in Europe but not in the United States for this indication; topical estrogen as adjunct) are listed under those categories. Medicines used in benign prostatic hyperplasia (alpha-1 blockers, 5α-reductase inhibitors, the BPH treatments umbrella) are collected separately, although the urgency component of BPH-associated lower-urinary-tract symptoms is sometimes treated with an OAB medicine in combination with a BPH medicine. The medicines used for nocturnal polyuria (desmopressin, the synthetic vasopressin analogue used at bedtime) are not OAB medicines per se but are mentioned where their indication overlaps the OAB phenotype. The neuromodulation devices (sacral, tibial) and the surgical procedures (augmentation cystoplasty, urinary diversion) are not medicines and are referenced only for clinical-decision context on the medicine pages.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.