Updating the evidence on drugs to treat overactive bladder: a systematic review

Abstract

IntroductionOveractive bladder (OAB) is a common condition, increasing with age and affecting quality of life. While numerous OAB drugs are available, persistence is low. We evaluated evidence published since 2012 to determine if newer drugs provided better efficacy and harm profiles.MethodsWe searched MEDLINE and the Cochrane Library from 2012 to September 2018 using terms for included drugs and requested information from manufacturers of included drugs. We performed dual review of all systematic review processes, evaluated study quality, and conducted meta-analyses using random effects models.ResultsIn addition to 31 older studies, we included 20 trials published since 2012 (N = 16,478; 4 good, 11 fair, and 5 poor quality). Where statistical differences were found, they were clinically small (reductions of < 0.5 episodes/day). Solifenacin plus mirabegron improved efficacy outcomes over monotherapy with either drug, but significantly increased constipation compared with solifenacin and dry mouth compared with mirabegron. Solifenacin reduced incontinence over mirabegron and tolterodine and urgency episodes over tolterodine. Mirabegron did not differ from tolterodine in efficacy but had significantly lower incidence of dry mouth than solifenacin or tolterodine. Fesoterodine showed significant improvements but also anticholinergic effects vs. tolterodine. Oxybutynin, solifenacin, and tolterodine had similar efficacy, but dry mouth led to greater discontinuation with oxybutynin. Blurred vision, cardiac arrhythmia, and dizziness were uncommon.ConclusionNew evidence confirms small, but clinically uncertain, differences among monotherapies and also between combination and monotherapy, regardless of statistical significance. While drugs mainly differed in incidence of dry mouth or constipation, none provided improved efficacy without increased harms.Electronic supplementary materialThe online version of this article (10.1007/s00192-019-04022-8) contains supplementary material, which is available to authorized users.

Overactive bladder syndrome: Management and treatment options

“…13,14 Non-selective agents are effective, with a success rate of >65%. 15 Unfortunately, these agents have several adverse effects that can make them relatively poorly tolerated. Fewer than 35% of patients are adherent to anticholinergic medications at 12 months post-commencement.…”

“…13,14 Dry mouth is a common complaint on starting the medication, and other bothersome side effects related to its mechanism of action include constipation and dry eyes. 15 Anticholinergic agents, primarily non-selective agents, should also be used cautiously in older patients because of their effects on cognitive function and possible interaction with other medications. 16 Prescribers should be aware that these agents are contraindicated for patients with glaucoma.…”

“…Beta-3 adrenergic receptor agonists upregulate sympathetic activity, thereby promoting detrusor smooth muscle relaxation and consequently reducing muscle spasms. 15 The current commercially available β3 adrenoceptor agonist is mirabegron (Table 3). It works via a different path to anticholinergic agents by relaxing the detrusor muscle, allowing higher bladder volumes before the need for urination.…”

Combination pharmacotherapy for the treatment of the overactive bladder syndrome: a new solution for an old problem?

“…To improve efficacy, providers may increase the dose of the drug [2], switch to a different antimuscarinic or try a combination of antimuscarinics to improve the therapeutic efficacy at the expense of producing higher rates of side effects [3].The β3-adrenergic receptor agonist mirabegron is another class of medication that has been in use since 2012 for treatment of OAB with similar clinical efficacy to antimuscarinics. Mirabegron acts through activation of the pre-junctional β3adrenoceptors of the urinary bladder.Treatment of OAB with β3-adrenergic receptor agonists has gradually gained acceptance in recent years as most clinical trials showed a better pharmacological profile and improved patient compliance compared with antimuscarinics [4][5][6].When pharmacotherapy of OAB with either antimuscarinics or β3-adrenergic receptor agonists does not achieve satisfactory results, then the next line of treatment becomes more invasive or inconvenient with increased risks of complications [7,8]. Invasive options include onabotulinumtoxin-A intradetrusor injection, sacral neuromodulation or posterior tibial nerve stimulation [8].…”

“…Treatment of OAB with β3-adrenergic receptor agonists has gradually gained acceptance in recent years as most clinical trials showed a better pharmacological profile and improved patient compliance compared with antimuscarinics [4][5][6].…”