Botulinum toxin A should not be first-line therapy for overactivebladder

Lesley K. Carr
2013 Canadian Urological Association Journal  
O veractive bladder (OAB) is a very prevalent condition in both men and women and has a significant negative impact on quality of life. 1 It is characterized by urgency to void and is generally associated with frequency of urination and nocturia. The coexistence of urge incontinence, OAB-wet, is more common in women. Overactive bladder may be associated with known neurologic conditions, such as spinal cord injury, multiple sclerosis and stroke (neurogenic OAB), or may occur in otherwise
more » ... ically intact individuals (idiopathic OAB). Traditional management of OAB should start with behavioural therapies (i.e., timed/prompted voiding, urge suppression, modification of type and timing of fluids and pelvic floor rehabilitation). Behavioural therapy has been shown to be effective at reducing urge incontinence alone or when combined with pharmacotherapy. 2 When behavioural strategies fail to achieve adequate control of OAB symptoms, anticholinergic medications are advocated next. There are a number of agents available; the selection should take into consideration a balance of efficacy and tolerability along with drug benefit coverage, when available. All prescription agents available in Canada have been shown to be effective in reducing OAB symptoms compared to placebo. While side effects are frequent with this group of medications (dry mouth, constipation, blurry vision amongst the most common), there are very few absolute contraindications: untreated narrow angle glaucoma, obstruction of the gastrointestinal or genitourinary system and myasthenia gravis. Botulinum toxin A (BTX A) has emerged as a new, effective treatment for refractory neurogenic and idiopathic OAB. Since early promising publications, 3-5 urologists have used BTX A in Canada for this purpose, but it continues to be done off-label as there is currently no formal approval for BTX A for OAB. Doses of 100 to 200 units of BTX A for idiopathic OAB and 200 to 300 units of BTX A for neu-rogenic OAB have been shown in placebo controlled trials to improve primary and secondary endpoints of urge incontinence episodes, maximum cystometrogram capacity, maximum detrusor pressure and quality of life. 4,6-8 The procedure is relatively simple and requires only an intravesical instillation of topical anesthetic in most patients. However, injection of BTX A into the detrusor remains an invasive procedure and carries risks of gross hematuria (6%-10%) 9 and urinary tract infection (7%-22%); 9 some patients also experience more bladder pain requiring anesthetic support. A frequent, dose-dependent complication of BTX A detrusor injections is increased post-void residual or urinary retention. The number of patients with idiopathic OAB treated with BTX A who converted to post-void residual related catheterization ranged from 5% to 21%. 10 The side effect of urinary retention may be of little concern for the neurogenic OAB patient who is already self-catheterizing, but for the idiopathic OAB patient, the potential for intermittent selfcatheterization may prohibit some patients from considering this option. In addition, rare systemic side effects, such as diffuse muscle weakness, have been reported (1%). 11 The etiology of this very rare complication is not known and it seems to be self-limiting and lasts from weeks to a couple of months. Finally, it is inherently expected that BTX A injections will need to be repeated in 3-to 12-month intervals. Studies have shown that repeated injections are effective, 11 however, there is theoretical concern that repeated injection may cause antibody formation over time with a loss of efficacy. Factors felt to increase the chance of antibody formation (based on experience with BTX A for cervical dystonia) are felt to be protein load (lower protein load 5 ng/100U in the formulation used since 1987), shorter duration between injections and larger doses. 11,12 A meta-analysis of published seroconversion estimates the rate of development of antibodies to BTX A for various conditions as follows: cervical dystonia (4 of 312), glabellar lines(2 of 718), OAB (0 of 22) and hyperhydrosis (4 of 871). 12
doi:10.5489/cuaj.643 fatcat:jhifuza2fje4jbokw5xeo24v3q