Overactive bladder syndrome (OAB) is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence, in the absence of urinary tract infection or other obvious pathology ¹ . The prevalence quoted in studies varies between 1 and 38.8% ² . OAB is projected to cost the United States $82.6 billion in 2020 ³ . It can have a negative impact on health-related quality of life and work productivity ⁴ . Those with bothersome symptoms have higher levels of anxiety and depression ⁴ . Treatment of OAB includes fluid management, behaviour modification, drug therapy, neuromodulation, and, rarely, surgery. In this review, we focus on recent advances in managing OAB.

Anticholinergic load is the cumulative effect of taking medication with anticholinergic properties ⁵ . Many elderly people take numerous medications for various chronic medical conditions, including urinary incontinence, that exert anticholinergic properties ⁵ . A high anticholinergic load can lead to physical and cognitive impairment in older adults ⁶ .

An observational retrospective cohort study of 113,311 patients aged over 65 years investigated falls, fractures, and mortality in those taking anticholinergics for OAB compared to those unexposed to anticholinergics ⁷ . There was a 1.28-fold increased risk of falls and fractures in individuals taking anticholinergics compared to controls. Past exposure to anticholinergics for OAB resulted in an increased risk of 1.14 for falls and fractures compared to controls.

A UK case controlled study of 40,770 adults aged over 65 years from GP data investigated the association between anticholinergics and dementia ⁸ . Drugs used for OAB were significantly associated with dementia. When the drug was used 4–10 years, 10–15 years, and 15–20 years prior to dementia diagnosis, there were odds ratios (ORs) of 1.23, 1.22, and 1.27 ( P <0.01), respectively. The drugs predominantly used were oxybutynin and tolterodine, which are both older, non-selective, generic medications used to treat OAB.

A US observational study investigated 350 patients aged 65 years or older over 3.2 years ⁹ . Use of anticholinergic medication was associated with an increased risk of transition from normal cognition to mild impairment (OR 1.15, P = 0.03). A prospective cohort study of 3,434 patients using anticholinergics found that 23% developed dementia over a mean of 7.3 years ¹⁰ . Former users of these drugs had similar risks compared to recent or continued use. Using oxybutynin for over 3 years had the greatest risk of dementia.

A systematic review found 15 out of 27 studies showed a positive correlation between anticholinergic load and mortality ⁶ . Ten studies found no correlation, and two studies showed mixed results, which may be related to follow up and the quality of the studies. The studies that showed a positive correlation were mainly of high quality.

With these effects in mind, care should be taken when prescribing OAB medication for older adults. Management of these patients should address mobility, functional impairment, lifestyle modification, urgency suppression, bladder retraining, patient and caregiver expectations, and life expectancy ¹¹ . Despite this, drug therapy may be needed if incontinence does not improve with these supportive measures. Trospium chloride is a quaternary amine anticholinergic, compared to the others, which are tertiary amines. This means trospium chloride is theoretically less likely to cross the blood–brain barrier, and this reduces central nervous system side effects ¹² . A randomised double-blind placebo-controlled trial of women aged over 50 years with OAB were treated with placebo or trospium chloride ¹³ . There was no significant difference in scores of cognitive tests between placebo and treatment at week 4.

Alternatively, mirabegron could be used as a treatment in this population. A phase IV study found that mirabegron improved symptoms of OAB in the elderly, with safety and tolerability consistent with known mirabegron safety profile ¹⁴ . A subanalysis of the BESIDE study in those aged over 65 years, which investigated the combination of solifenacin and mirabegron, found no difference between solifenacin 5 mg plus mirabegron 50 mg compared to solifenacin 10 mg ¹⁵ . The authors argue that combination therapy may be better for the elderly rather than solifenacin 10 mg, as the latter may increase the anticholinergic load. Another study found that there was no significant change in the Montreal Cognitive Assessment from baseline to week 12 in elderly patients using mirabegron ¹⁶ .

Genitourinary syndrome of menopause (GSM) is the new terminology for vulvovaginal atrophy and urinary symptoms, which may occur together or independently ²⁴ . There is evidence to show that oestrogen deficiency may increase the risk of OAB ²⁵ . A meta-analysis reviewed 10 randomised placebo-controlled trials ²⁶ . It found that oestrogen therapy was superior to placebo for frequency, nocturia, and urgency incontinence. Vaginal oestrogens were better than systemic oestrogens for urinary urgency.

Combination therapy in the form of vaginal oestrogens and anticholinergics may help improve OAB symptoms. One study investigated solifenacin, with or without intra-vaginal promestriene, in 104 postmenopausal women over 12 weeks ²⁷ . Both groups had a significant reduction in frequency, urgency, urgency incontinence episodes, and nocturia but without a significant difference between the groups. The combination group did have a significantly better reduction in OAB symptom score questionnaire ( P = 0.016) compared to solifenacin alone.

Another study investigated fesoterodine with or without vaginal premarin ²⁸ . Both groups had improvements in OAB symptoms. The combination group had better improvement in OAB symptom score questionnaire, OAB health-related quality of life score, and sexual quality of life questionnaire scores.

Ospemifene is a selective oestrogen receptor modulator that has an oestrogen agonist effect and can be used by those in whom oestrogen therapy may be contraindicated ²⁹ . A study of 105 patients found a significant improvement in frequency, nocturia, urgency, and urgency incontinence ²⁹ . There were also significant improvements in OAB questionnaire scores. A retrospective review of 46 women using ospemifene for GSM found a significant improvement in frequency, nocturia, urgency, and urgency incontinence ³⁰ .

OnabotulinumtoxinA (“botox”) helps those with OAB by inhibiting acetylcholine release, leading to bladder detrusor muscle paralysis ³¹ . A systematic review and meta-analysis has shown significant incontinence-free episodes ( P <0.001), reduction in urinary incontinence episodes ( P <0.001), and reduction in mean number of micturitions ( P <0.001) ³² .

A recent meta-analysis of 19 studies found that doses of 200 U and 300 U were more effective than placebo for the treatment of neurogenic detrusor overactivity, with minimal but manageable side effects ³³ . A double-blind, randomised, placebo-controlled trial investigated different doses of botulinum toxin ³⁴ . A dose greater than 150 U had minimal additional improvement in symptoms, with increased risk of urinary retention and need to self-catheterise. The authors recommend using 100 U, which they feel balances symptom improvement and safety profile. The National Institute for Health and Care Excellence (NICE), which provides health guidance in the United Kingdom, recommends using 100 U ³⁵ .

A recent study investigated bladder trigone-involved injections against those with trigone-sparing injections ³⁶ . A total of 103 patients received 100 U and were followed up at 6 months. Both groups had a reduction in OAB outcome measures, but there was no difference between groups. The trigone-involved group had a higher incidence of urinary tract infection and voiding difficulties.

Selective bladder denervation (SBD) is a procedure that involves radiofrequency ablation of the sub-trigone area of the bladder, which contains afferent sensory nerves ⁵⁴ . The device is applied to the trigone under cystoscopic guidance. The thermal delivery probe is placed along the left border of the trigone 5 mm below the ureteric orifice. The electrodes are then advanced 3 mm into the urothelium and ablation begins. This is repeated on the right border of the trigone and again in numerous points in between these two borders.

A total of 63 patients with refractory OAB underwent this treatment ⁵⁴ . At 12 weeks, there were significant reductions in frequency, urgency episodes, and urgency incontinence episodes. There was a significant improvement in OAB questionnaire scores and quality of life ( P <0.01). Ablation for 60 seconds had significantly greater improvement in urgency incontinence episodes and quality of life scores than ablation for 10 seconds, with no significant difference in post void residuals. Post procedure pain was minimal over 5 days. One woman had a serious adverse event of obstruction of the left ureter, leading to hydronephrosis and pyelonephritis 8 days later. Lower urinary tract infection occurred in 9.5%. No patients had urinary retention requiring catheterisation.

This study was performed under sedation or a general anaesthetic. The authors are planning to study the use of local anaesthesia. This human feasibility study was also non-randomised, which introduces bias. The results and safety profile are promising, but larger controlled studies with longer follow up are needed.

Light amplification by stimulated emission of radiation (laser) was first described by Einstein in 1917 ⁵⁵ . It is used for different medical reasons. The two most commonly used lasers are microablative fractional CO ₂ laser (SmartXide ²-V ²LR, MonaLisa Touch; DEKA, Florence, Italy) and non-ablative photothermal erbium:YAG (Er:YAG) laser (Fotona Smooth XS; Fotona, Ljubljana Slovenia) ⁵⁵ . The laser causes thermomodulation by heating and (in the case of the CO ₂ laser) ablating columns of tissue ⁵⁵ .

A prospective observational pilot study ⁵⁶ enrolled 30 postmenopausal women with vulvovaginal atrophy and OAB. They were treated with CO ₂ laser, with three treatments 30 days apart. The procedure was performed in an ambulatory setting without analgesia or anaesthetic. There were significant improvements in bladder diary values ( P <0.0001), number of urgency episodes ( P <0.0001), urgency incontinence episodes ( P = 0.006), and OAB questionnaire scores ( P <0.0001). There were no adverse events.

Another study recruited 150 postmenopausal patients to Er:YAG laser (three treatments, 1 month apart), an anticholinergic (fesoterodine), or mirabegron ⁵⁷ . There were significant improvements in OAB symptom scores in all three groups ( P <0.001), but only the laser group reported improvement in vaginal health index scale at 12 months. There were no adverse events with the laser. A further study of 30 women completed two sessions of Er:YAG laser treatment ⁵⁸ . There were significant improvements in OAB symptom scores at 3 months ( P = 0.027) but not at 12 months ( P = 0.576). No major adverse events occurred. Most described mild pain and few had vaginal discharge or spotting for several days.

At present, there is little evidence to support the use of laser for OAB. Further larger controlled studies are needed.

This article highlights the recent advances in the management of OAB. When prescribing for older adults, care is needed because of the risks associated with a high anticholinergic load. Alternative treatments may be needed, including mirabegron, which does not add to the load. Vibegron is a promising beta-3 agonist that has potentially fewer drug interactions but is licensed only in Japan. Further studies are needed for PDE5Is. Botulinum toxin has been shown to be a good treatment option. There have been promising developments in implantable devices for both PTNS and SNM, with the latter rechargeable device being implemented soon in the UK. SBD and laser are new technologies that show improvements in OAB, but further studies are needed before they can be recommended as treatments.