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What Is the Most Effective Treatment for Nocturia Or Nocturnal Incontinence in Adult Women?

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What Is the Most Effective Treatment for Nocturia Or Nocturnal Incontinence in Adult Women? EUF-869; No. of Pages 11 E U R O P E A N U R O L O G Y F O C U S X X X ( 2 0 1 9 ) X X X – X X X ava ilable at www.sciencedirect.com journa l homepage: www.europeanurology.com/eufocus Review What Is the Most Effective Treatment for Nocturia or Nocturnal Incontinence in Adult Women? a, b c d Dina Bedretdinova *, David Ambu¨hl , Muhammad Imran Omar , Vasileios Sakalis , e f g h Nikesh Thiruchelvam , Marc Schneider , Arjun Nambiar , Ruud Bosch a b c INSERM CESP U1018, Villejuif, France; Department of Urology, University Hospital Bern, Inselspital Anna Seiler-Haus, Bern, Switzerland; European d Association of Urology Guidelines Office, Arnhem, The Netherlands; Department of Urology, General Hospital of Thessaloniki Agios Pavlos, Thessaloniki, e f Greece; Department of Urology, Cambridge University Hospitals NHS Trust, Cambridge, UK; Department of Urology, University Hospital Bern, Inselspital g h Anna Seiler-Haus, Bern, Switzerland; Department of Urology, Freeman Hospital, Newcastle-upon-Tyne, UK; Department of Urology, University Medical Centre Utrecht, Utrecht, The Netherlands Article info Abstract Article history: Context: Nocturia is a prevalent symptom with varied aetiology and no consensus on treatment options. Accepted January 28, 2020 Objective: We systematically reviewed evidence comparing the benefits and harms of various treatment options for nocturia or nocturnal incontinence in women. Associate Editor: Evidence acquisition: Literature search was performed using Embase, Medline, and Cochrane Malte Rieken databases (from 1 January 1946 to 26 September 2017), following the methods detailed in the Cochrane Handbook. The protocol was registered with PROSPERO. Certainty of evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation Keywords: (GRADE) approach. Antimuscarinics Evidence synthesis: The literature search identified 3573 citations, of which 11 full-text articles Desmopressin were included. Three studies on desmopressin and four on antimuscarinics provided evidence of Nocturia improving nocturia symptoms. Four studies onbehavioural treatment providedlimited evidence and controversial results. One study on oestrogen did not prove the benefit of any mode of Systematic review administration, and onesmall studyon functional magnetic stimulationprovided some evidence Treatment of effectiveness in nocturia. One randomised controlled trial (RCT; 141 participants) reported a Women statistically significant difference between the desmopressin and placebo groups (desmopressin patients experienced 0.75 [95% confidence interval {CI} 0.47–1.03] nocturia episodes less than those experience by the placebo group; certainty of evidence = low). The only RCT on antimuscarinics in women with nocturia reported that oxybutynin reduced the number of nocturia episodes by 0.3 (95% CI –0.02 to 0.62) versus placebo. In one RCT comparing tolterodine with the combination of tolterodine with behavioural therapy, there was significant change from baseline nocturnal incontinence episodes in both groups. Conclusions: There is some evidence that desmopressin and antimuscarinics are effective treatment options for nocturia; however, there is very limited evidence for other treatment options. The findings should be interpreted with caution as there were some methodological flaws in the included studies, particularly outcome heterogeneity. Patient summary: This review identified several medical treatments for nocturia in women, such as desmopressin and antimuscarinics, which appear to improve the severity of the condition. © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. 82, rue du General Leclerc, 94276 Le Kremlin-Bicetre Cedex, France. Tel. +33(0)1 45 21 24 37, Mob: +33(0)6 72 16 25 70, Fax: +33(0)1 45 21 20 75. E-mail address: [email protected] (D. Bedretdinova). https://doi.org/10.1016/j.euf.2020.01.012 2405-4569/© 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved. Please cite this article in press as: Bedretdinova D, et al. What Is the Most Effective Treatment for Nocturia or Nocturnal Incontinence in Adult Women?. Eur Urol Focus (2020), https://doi.org/10.1016/j.euf.2020.01.012 EUF-869; No. of Pages 11 2 E U R O P E A N U R O L O G Y F O C U S X X X ( 2 0 1 9 ) X X X – X X X 1. Introduction nocturia or nocturnal incontinence in terms of improving symptom severity and quality of life in adult women. Nocturia is defined by the International Continence Society (ICS) as “waking to pass urine during the main sleep period”. 2. Evidence acquisition Nocturnal incontinence is a complaint of intermittent incontinence that occurs during the main period of sleep This SR was undertaken under the auspices of the EAU. We after the age of 3–5 yr at which bladder control usually followed the Preferred Reporting Items for Systematic occurs [1]. Nocturnal polyuria (NP) is defined as passing Reviews and Meta-analysis (PRISMA) guidance and the large volumes of urine during the main sleep period that Cochrane Handbook for SRs of interventions [14,15]. The should be quantified using a bladder diary [2]; some of the protocol was registered at PROSPERO (CRD42017058997). definitions propose thresholds such as nocturnal urine The databases searched were the Embase, OVID Medline > – volume 20 33% of total 24-h urinary volume. Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Nocturia is a prevalent symptom in men and women of all Ovid MEDLINE(R) Daily and Ovid MEDLINE(R), EBM age groups. This paper will focus on women only. According to Reviews—Cochrane Central Register of Controlled Trials, and Bosch and Weiss [3], one in five or six younger people consis- EBM Reviews—Cochrane Database of Systematic Reviews from tently wake to void at least twice each night. Up to 60% of older 1946 to September 2017. Studies were limited to full-text people void two or more times nightly [3]. Age is one of the articles published in English, French, Spanish, Russian, and most important risk factors. There is some controversial evi- German language. The complete search strategy is provided dence about gender as a risk factor. There is some evidence in the Supplementary material (Literature search strategy). The about the association with metabolic syndrome, obesity, dia- detailed PICO search strategy is shown in Table 1. betes, cardiac disease, other conditions and ethnicity (African- American race) [4,5].Althoughnocturiaisnotalife-threatening 2.1. Data collection and analysis condition itself, there is a risk of increased mortality in some patients due to hip fractures caused by risk of falls when getting The study selection process is described in Fig. 1 [15]. All up to urinate [6]. Economic burden of nocturia is important, stages of selection were done with Covidence (www. frequently leading to repeated consultations, diagnostic pro- covidence.org). cedures, medications, and therapies, with costs adding up with Two review authors (D.B. and D.A.) independently assessed every patient. Sleep disturbance/bother and impact on quality the risk of bias (RoB), using the Cochrane RoB assessment tool of life are the most important reasons for consultation [7]. for randomised controlled trials (RCTs) [16]. RoB in non-RCT Concerning the optimal treatment of nocturia in women, was evaluated with an extra item to assess the risk of there is no consensus due to the multifactorial pathophysiol- confounding [17,18]. Study authors were contacted to provide ogy (common symptom in different diseases).Theunderlying missing information. Any disagreements were resolved by causes may be urological, for example, lower urinary tract discussion or by consulting a third review author (I.O.). symptoms and neurogenic voiding dysfunction, or nonuro- Meta-analysis, funnel plot interpretation, or assessment logical, such as chronic heart failure and sleep apnoea, or of heterogeneity and sensitivity analyses was planned, but hormonal in origin [8]. The optimal treatment was investi- was not feasible due to paucity of data. Furthermore, the gated previously, but evidence was limited [9–13]. Currently studies used different dosages and modes of administration available treatments include antidiuretics and antimuscari- of drugs. Quantitative synthesis was not undertaken for nics. Desmopressin is an antidiuretic, working at the level of nonrandomised studies. Instead, we used the narrative the renal collecting duct, binding to the V2 receptors present synthesis [14,19] approach to summarise the results. inthedistal collectingtubules.Itisthoughttoworkinpatients The Grading of Recommendations Assessment, with NP by decreasing diuresis. Muscarinic receptor Development and Evaluation (GRADE) approach was used antagonists or antimuscarinics, such as darifenacin, fesoter- for assessing the certainty of evidence. The following out- odine, oxybutynin, propiverine, solifenacin, tolterodine, and comes were selected for the “summary of findings” table: trospium chloride, block the activity of muscarinic acetylcho- line receptor. Some of them are more specific to the M3 1 receptor, which is most prevalent in detrusor muscle; some Number/frequency of nocturia episodes are less specific and act on all receptor subtypes (M1, M2, and 2 NPI (NP Index; nocturnal urine volume/24-h urine M3), leading to more side effects. volume [%]) There is no consensus on which treatment option is most 3 Nocturnal urinary volume effective in women with nocturia or nocturnal inconti- 4 Nocturnal urinary incontinence
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