AFJOG

REVIEW African Journal of Obstetrics and Gynaecology | Volume 2 | Issue 1 | 2024 | Advanced Management Options for Refractory Overactive Bladder Antimuscarinic drugs (anticholinergic) are considered the gold standard and the second line of treatment in the management of OAB patients. 9, 11, 12 Anticholinergic drugs work by relaxing the detrusor by inhibiting afferent nerve activity at the urothelial sensory receptors and by producing a competitive inhibition on cholinergic-muscarinic receptors resulting indetrusormusclecontractions. 9 Asystematic review of 32 trials involving 6800 participants found anticholinergic drugs effective in improving the symptoms and consequent quality of life of patients with OAB. 17 The effectiveness of anticholinergic was also proven effective in other systematic reviews and metanalyses. 18-20 Despite the proven efficacy of antimuscarinic drugs, discontinuation is common due to side effects such as dry mouth and constipation, and more severe side effects may include cognitive and cardiovascular symptoms. 21, 22 The side effects can be mitigated by starting with small doses and closely monitoring the patients for one to three months as the dosage increases. 23 While there are no differences between different types of anticholinergic drugs in terms of effectiveness, extended-release (ER) has a higher safety profile and fewer side effects compared to immediate- release (IR). 13, 16, 24 β3-agonists can also be used as a second- line drug therapy for patients who are not responsive to antimuscarinic or cannot tolerate side effects. β3-agonists are as effective as antimuscarinic drugs but with fewer side effects. 9, 11-13 ADVANCED MANAGEMENT OF OAB Advanced treatment options should be considered for patients who are unresponsive to conservative treatment modalities. This is referred to as refractory OAB. Patients who have not responded to full doses of antimuscarinic drugs and patients who have discontinued drug therapy due to side effects are ideal candidates for advanced therapy. 9 These treatment modalities should be discussed with the patient with emphasis on efficacy, safety and time commitment. 9 In the public sector, there might be challenges in having these treatment modalities; however, in the private sector, these options are readily available to those covered by medical insurance. Advanced treatment option ranges from non-invasive acupuncture, posterior tibial nerve stimulation (PTNS) and botulinum toxin A injections to invasive surgically implanted devices like sacral neuromodulation (SNM). 9 OnabotulinumtoxinA (Botox): The intravesical injection of OnabotulinumtoxinA (OBTA) is considered one of the third-line treatment options. 23 OBTA is a neurotoxin that is acquired from an anaerobic bacteria Clostridium Botulinum. OBTA works by inhibiting acetylcholine release from presynaptic neurons and adenosine triphosphate and P substance release at the level of the urothelium. 23 This results in decreased acetylcholine at the neuromuscular junction, which leads to the paralysis of the detrusor and subsequently results in less overactive bladder symptoms. 23 OBTA is administered cystoscopically by directly injecting into the bladder wall on multiple sites, as shown in figure 1. OBTA is effective within two weeks of injection, and the duration of its effect is reported to be 3 to 12 months. The effectiveness of the injections increases with the number of doses; however, the risk of side effects also increases. 11-13, 24, 25 Research shows that OBTA treatment results in the improvement of symptoms and quality of life. A study that examined the efficacy of OBTA in 100 cases found that 88% of the patients improved after 4 to 12 weeks. 26 The improvement of symptoms lasted between six and nine months, and the new administration of OBTA was required. 26 In another study that examined the effects of multiple injections prospectively found that repeat injections sustained the improvements; however, there was an attrition rate of 37% due to insufficiency and temporary urinary retention. 27 There have been some debates regarding the dose of OBTA required for efficacy and minimal adverse events. A clinical trial that compared outcomes of different doses of Botox found that 100 U of OBTA had a 73.3% success rate and had fewer adverse events compared to 150 U or 200 U; thus, the standard dose is 100 U. 28 Despite the efficacy of OBTA in improving the symptoms of daily frequency, urgency, and urinary incontinence, there is a high incidence of adverse events such as urinary tract infection and urinary retention. 29 A systematic review of the outcomes of OBTA found that the incidence of urinary tract infections and a need for a catheter was significantly higher in the group that received Botox injections compared to the placebo. 30 Figure 1 Depicts sites of OnabotulinumtoxinA injections in the bladder. ©2024 UpToDate, Inc. and/ or its affiliates. Neuromodulation: Neuromodulation is another alternative for OAB patients who do not respond well to conservative and pharmacological management. Neuromodulation is a minimally invasive surgical procedure aiming to treat OAB symptoms by stimulating the S3 nerve root with a percutaneously implantable device under fluoroscopic guidance, which generates electrical impulses that regulate bladder and pelvic floor function. SNM offers electrical stimulation of the sacral nerves to modulate the neural reflexes that influence the bladder, sphincter, and pelvic floor. The aim of implementing SNM is the reduction in incontinence accidents, return to normal toilet habits, less incontinent product usage, less medication usage, and improved quality of life. There is a range of devices that are used in SNM. The most commonly used is the InterStim Voltage-driven non-rechargeable device. There are also current-driven rechargeable devices called Axonics. 31 An FDA-mandated post-approval study on Intersim found that 80% of the patients had a successful test phase and a 5-year therapeutic African J urnal of Obst trics and Gynaecology | Volume 2 | Issue 1 | 2024 | 12