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Int Urogynecol J. 2013 Oct 25. [Epub ahead of print] 1. use for female overactive bladder in the ambulatory setting in the United States. Ju R1, Garrett J, Wu JM. Author information

Abstract INTRODUCTION AND HYPOTHESIS: Our objective was to estimate the prevalence and sociodemographic factors associated with anticholinergic medication use by adult women for overactive bladder (OAB) in the United States. METHODS: We conducted a cross-sectional study using the 2009 National Ambulatory Medical Care Survey database (NAMCS). We included women aged 18 years and older and identified visits for which anticholinergic for OAB were in active use. We evaluated the prevalence of medications used and estimated the use of short-acting versus long-acting drugs. We also assessed variables associated with anticholinergic use, (age, race/ethnicity, insurance, geographic location) using survey weights in the analysis to estimate national data. RESULTS: In 2009, adult women made 516.8 million outpatient office visits. Of these, 8.1 million (1.6 %) were associated with an OAB anticholinergic medication (annual rate 68 per 1,000 women). Women who used were predominantly insured by Medicare (61.0 %) and were older than those not using anticholinergic medications (70.0 ± 1.1 vs. 53.0 ± 0.5, p < 0.001). No racial or ethnic differences were evident between the two groups. (33.8 %) and (33.1 %) were the most commonly reported medications, followed by solifenacin (19.5 %), darifenacin (9.3 %), and trospium (4.4 %). Long-acting anticholinergics were used more often than short-acting medications (53.8 % vs. 46.3 %, respectively, p < 0.001). CONCLUSIONS: Annually, more than 8 million outpatient visits occur in which adult women in the United States are using an OAB anticholinergic medication. Despite the abundance of newer-generation medications, tolterodine and oxybutynin remain the most commonly prescribed anticholinergic drugs for OAB. Solifenacin is the most popular newer-generation anticholinergic drug.

PMID: 24158462 [PubMed - as supplied by publisher]

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BJU Int. 2010 Aug;106(4):506-14. doi: 10.1111/j.1464-410X.2009.09160.x. Epub 2010 Feb 3. 2. The cost-effectiveness of solifenacin vs , oxybutynin immediate-release, propiverine, tolterodine extended-release and tolterodine immediate-release in the treatment of patients with overactive bladder in the UK National Health Service. Cardozo L1, Thorpe A, Warner J, Sidhu M. Author information

Abstract OBJECTIVE: To assess the cost-effectiveness of solifenacin vs other antimuscarinic strategies commonly used in UK clinical practice, based on the results of a recent published review. METHODS: Overactive bladder (OAB) syndrome is characterized by symptoms of urgency, frequency, incontinence and nocturia. Pharmacological treatment comprises oral antimuscarinic agents, which are divided into older-generation treatments, including oxybutynin, and new-generation treatments, comprising solifenacin, tolterodine, darifenacin and fesoterodine. The latter have reduced central nervous system penetration and have better selectivity for the M3 subclass of receptors, resulting in improved tolerability. A recent systematic review and meta-analysis of the efficacy and safety of antimuscarinics provided an opportunity for an economic evaluation of these agents using a rigorous assessment of efficacy. A cost-utility analysis was undertaken using a 1-year decision-tree model. Treatment success was defined separately for urgency, frequency and incontinence, with efficacy data taken from the recent review. Treatment persistence rates were taken from the Information Management System database. Utility values for the calculation of quality-adjusted life-years (QALYs) were taken from published sources. The analysis included costs directly associated with treatment for OAB, i.e. antimuscarinic therapy, consultations with general practitioners, and outpatient contacts. Resource use was based on expert opinion. Costs were reported at 2007/2008 prices. Extensive deterministic and probabilistic analyses were conducted to test the robustness of the base-case results. RESULTS: Solifenacin was associated with the highest QALY gains (per 1000 patients) for all three outcomes of interest, i.e. urgency (712.3), frequency (723.1) and incontinence (695.0). Solifenacin was dominant relative to fesoterodine, tolterodine extended-release (ER) and tolterodine immediate-release (IR), and cost-effective relative to propiverine ER for urgency, frequency and incontinence. Solifenacin was not found to be cost-effective relative to oxybutynin IR for the frequency and incontinence outcomes, with an incremental cost- effectiveness ratio of > pound30,000/QALY threshold. CONCLUSIONS:

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Solifenacin provided the greatest clinical benefit and associated QALYs for all three outcomes of interest across all therapies considered, and to be either dominant or cost- effective relative to all other new-generation agents, but not cost-effective relative to oxybutynin for frequency and incontinence.

Comment in The cost-effectiveness of solifenacin vs fesoterodine, oxybutynin immediate-release, propiverine, tolterodine extended-release and tolterodine immediate-release in the treatment of patients with overactive bladder in the UK National Health Service. [BJU Int. 2010]

PMID: 20132203 [PubMed - indexed for MEDLINE]

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Urologe A. 2009 Mar;48(3):245-9. doi: 10.1007/s00120-008-1915-y. 3. [Anticholinergic treatment of overactive bladder syndrome. Is it all the same?]. [Article in German] Schneider T1, Michel MC. Author information

Abstract Anticholinergic therapy is the first-line therapy for overactive bladder (OAB) syndrome. Especially in the last years, the number of available substances has increased because of the launch of solifenacin, darifenacin, and fesoterodine. Additionally, slow-release and transdermal formulations have led to a large variety of available treatment options. The efficacy of all substances has been proven in randomised, double-blind studies, and reviews and meta-analyses have also underlined the efficacy of all available anticholinergics and have been updated regularly. All available drugs are efficacious for OAB treatment, and clinically relevant differences among them have not been proven consistently. Moreover, age, gender, and the type of OAB (dry vs. wet) seem to lack clinically relevant impact on the efficacy of OAB treatment. The various drugs are similar in tolerability, with the exception of more dry mouth and central nervous effects with slow-release oxybutynin. Knowledge of pharmacokinetic properties of the individual substances is important in order to choose the right therapy for each patient.

PMID: 19145428 [PubMed - indexed for MEDLINE]

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Eur Urol. 2008 Sep;54(3):543-62. doi: 10.1016/j.eururo.2008.06.047. Epub 2008 Jun 20. 4. The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis. Chapple CR1, Khullar V, Gabriel Z, Muston D, Bitoun CE, Weinstein D. Author information

Abstract CONTEXT: Antimuscarinic agents are currently the first-line pharmacotherapy for overactive bladder. OBJECTIVES: A systematic review published in 2005 was updated, including data on a newly licensed antimuscarinic (fesoterodine). The primary aim of this study was to systematically review evidence on the efficacy of licensed administration of antimuscarinic treatments in overactive bladder from randomised controlled trials. Secondary aims were to review evidence on tolerability and safety and health-related quality of life (HRQL). EVIDENCE ACQUISITION: All relevant data sources from randomised controlled trials were searched, and two independent reviewers considered publications for inclusion and extracted relevant data. Meta-analysis was used to pool efficacy, tolerability, safety, and HRQL outcomes by treatment. Efficacy was measured by continent days, mean voided volume, urgency episodes, and micturition frequency. Tolerability and safety were measured by means of adverse event and withdrawal rates. HRQL was measured by various instruments. EVIDENCE SYNTHESIS: An additional 1118 references were retrieved with data on 83 studies extracted. Antimuscarinics were found to be more effective than placebo. Tolerability was good; few of the antimuscarinics were found to have significantly higher withdrawal rates in comparison to placebo. No serious adverse event for any product was statistically significant compared to placebo. Dry mouth (mild, moderate, severe) was the most commonly reported adverse event (29.6% on treatment vs 7.9% on placebo), followed by pruritus (15.4% on treatment vs 5.2% on placebo). Improvements were seen in HRQL with treatment by darifenacin, fesoterodine, oxybutynin transdermal delivery system, propiverine extended release (ER), solifenacin, tolterodine ER and immediate release, and trospium. Limitations of the study include restrictions on the types of patients typically included in overactive bladder trials and topics that have not been adequately addressed in the current antimuscarinic literature. CONCLUSIONS: Antimuscarinics are efficacious, safe, and well-tolerated treatments that improve HRQL. Profiles of each drug and dosage differ and should be considered in making treatment choices.

Comment in

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Re: Christopher R. Chapple, Vik Khullar, Zahava Gabriel, et al. The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis. Eur Urol 2008;54:543-62. [Eur Urol. 2009] Re: Christopher R. Chapple, Vik Khullar, Zahava Gabriel, et al. The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis. Eur urol 2008;54:543-62. [Eur Urol. 2009]

PMID: 18599186 [PubMed - indexed for MEDLINE]

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BJU Int. 2007 Nov;100(5):987-1006. 5. Muscarinic receptor antagonists for overactive bladder. Abrams P1, Andersson KE. Author information

Abstract Overactive bladder (OAB) is a syndrome characterized by urinary urgency, with or without urgency urinary incontinence, usually with frequency and nocturia. OAB symptoms are often associated with detrusor overactivity (DO). Like OAB symptoms, the prevalence of DO increases with age and can have a neurogenic and/or myogenic aetiology. Bladder outlet obstruction can be a contributing factor in DO, possibly through denervation of the detrusor and supersensitivity of muscarinic receptors to acetylcholine, although the prevalence of OAB is similar in men and women across age groups. Acetylcholine is the primary contractile neurotransmitter in the human detrusor, and antimuscarinics exert their effects on OAB/DO by inhibiting the binding of acetylcholine at muscarinic receptors M(2) and M(3) on detrusor smooth muscle cells and other structures within the bladder wall. Worldwide, there are six antimuscarinic drugs currently marketed for the treatment of OAB: oxybutynin, tolterodine, propiverine, trospium, darifenacin, and solifenacin. Each has demonstrated efficacy for the treatment of OAB symptoms, but their pharmacokinetic and adverse event profiles differ somewhat due to structural differences (tertiary vs quaternary amines), muscarinic receptor subtype selectivities, and organ selectivities. Antimuscarinics are generally well tolerated, even in special populations (e.g. men with bladder outlet obstruction, elderly patients, children). The most frequently reported adverse events in clinical studies of antimuscarinics are dry mouth, constipation, headache, and blurred vision; few patients withdraw from clinical trials because of adverse events. Development of an antimuscarinic with functional selectivity for the bladder would reduce the occurrence of antimuscarinic adverse events. The therapeutic potential of several other agents, such as

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alpha(3)-adrenoceptor agonists, purinergic receptor antagonists, phosphodiesterase inhibitors, neurokinin-1 receptor antagonists, opioids, and Rho-kinase inhibitors, is also under investigation for the treatment of OAB.

PMID: 17922784 [PubMed - indexed for MEDLINE]

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