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Nonantimuscarinic treatment for overactive bladder: a systematic review

Olivera CK, Meriwether K, El-Nashar S, Grimes CL, Chen CC, Orejuela F, Antosh D, Gleason J, Kim-Fine S, Wheeler T, McFadden B, Balk EM, Murphy M; Systematic Review Group for the Society of Gynecological Surgeons

American Journal of Obstetrics and Gynecology, Volume 215, Issue 1, July 2016, Pages 34 – 57

Commented by Prof. Karl-Erik Andersson

Is non-antimuscarinic treatment for overactive bladder effective in nocturia?

It is well documented that among lower urinary tract symptoms (LUTS), particularly in the elderly population, nocturia is often the most frequent and bothersome symptom (Bosch and, 2010; Cornu et al., 1012; Hofmeester et al., 2014). Nocturia is one of the symptoms included in the overactive bladder (OAB) syndrome, and treatments directed against OAB, such as antimuscarinics, could be expected to have some effect on nocturia. However, a main cause of nocturia is nocturnal polyuria and it may be difficult to demonstrate a clinically significant effect on nocturnal voiding of drugs that do not specifically affect this condition, but are meant for urgency and detrusor overactivity (Dmochowski and Wein, 2012).  Consequently, there is limited evidence that antimuscarinics in general are efficient for the specific management of nocturia in the context of OAB, and even if positive effects have been reported for some of the drugs, e.g., imidafenacin, which was reported to decrease both the number of urinations and to reduce nocturnal urine production (Homma et al., 2013), antimuscarinics often lack marked efficacy. It is likely that at least in part, the lack of efficacy is related to the heterogeneous group of patients being treated and a failure to exclude those with nocturnal polyuria (Cornu et al., 2012). 

In women, a recent systematic review confirmed that antimuscarinics used in OAB treatment often reduce voids by less than 2 episodes a day and only rarely result in complete resolution of symptoms, have a poor compliance, low patient satisfaction, and bothersome side effects (Reynolds et al., 2015).  However, there are many non-antimuscarinic alternatives for treatment of OAB, and it may be questioned if any of these treatments have any advantages over antimuscarinics in the treatment of nocturia?

Olivera et al. (2016) performed a systematic review to determine the efficacy and safety of non-antimuscarinic treatments for women with OAB.  They included adults (>18 years old) with OAB symptoms of urgency, frequency, nocturia, urgency urinary incontinence (UUI), diagnoses of refractory OAB, refractory UUI, OAB syndrome, and accepted any study (retrospective, prospective, cohort, randomized, controlled trials, case series, case control, cross-sectional, crossover) in which there were 2 arms and a number greater than 100, if at least 1 of the arms was a non-antimuscarinic therapy for overactive bladder. There were 156 articles screened and 99 of these met all criteria for inclusion in the systematic review. The final interventions and comparators were (1) behavioral therapy (including weight loss, fluid management, diet modification, bladder training, and pelvic floor muscle training, alternative medical therapy (most commonly acupuncture), (3) biofeedback, (4) botulinum toxinA formulations, (5) mirabegron, (6) magnetic stimulation, (7) vaginal electrical stimulation, (8) sacral neuromodulation, and (9) posterior tibial nerve therapy.

 After analysing the different alternatives, Olivera et al. (2016) concluded that non-antimuscarinic treatments may be equivalent to or, in some cases, preferable to typical antimuscarinic medications in the treatment of OAB symptoms, including nocturia. However, none of the treatments seemed to be specifically effective for treatment of nocturia, even if they offered advantages over antimuscarinics with respect to adverse effects.

Several randomized trials have demonstrated that posterior tibial nerve stimulation have effects on OAB symptoms, including nocturia, equal to or better those of antimuscrinics, but with minimal side effects (Peters et al., 2009: Leong et al., 2013; Vecchioli-Scaldazza et al., 2013; Moossdorff-Steinhauser and  Berghmans, 2013). This does not imply that posterior tibial nerve stimulation is a specific treatment of nocturia, but supports that nocturia within the frame of OAB can be successfully treated with other alternatives than antimuscarinics. Among the non-antimuscarinic treatment alternatives, Olivera et al. (2016) concluded that OAB patients probably will receive the most benefit from reversible treatments with minimal side effects that are proven to have good efficacy in short time frames. This may be best demonstrated by physiotherapy (optimally with biofeedback) and posterior tibial nerve stimulation.

Abstract
 

The purpose of the study was to determine the efficacy and safety of nonantimuscarinic treatments for overactive bladder. Medline, Cochrane, and other databases (inception to April 2, 2014) were used. We included any study design in which there were 2 arms and an n > 100, if at least 1 of the arms was a nonantimuscarinic therapy or any comparative trial, regardless of number, if at least 2 arms were nonantimuscarinic therapies for overactive bladder. Eleven reviewers double-screened citations and extracted eligible studies for study: population, intervention, outcome, effects on outcome categories, and quality. The body of evidence for categories of interventions were summarized and assessed for strength. Ninety-nine comparative studies met inclusion criteria. Interventions effective to improve subjective overactive bladder symptoms include exercise with heat and steam generating sheets (1 study), diaphragmatic (1 study), deep abdominal (1 study), and pelvic floor muscle training exercises (2 studies). Pelvic floor exercises are more effective in subjective and objective outcomes with biofeedback or verbal feedback. Weight loss with diet and exercise, caffeine reduction, 25-50% reduction in fluid intake, and pelvic floor muscle exercises with verbal instruction and or biofeedback were all efficacious. Botulinum toxin A improves urge incontinence episodes, urgency, frequency, quality of life, nocturia, and urodynamic testing parameters. Acupuncture improves quality of life and urodynamic testing parameters. Extracorporeal magnetic stimulation improves urodynamic parameters. Mirabegron improves daily incontinence episodes, nocturia, number of daily voids, and urine volume per void, whereas solabegron improves daily incontinence episodes. Short-term posterior tibial nerve stimulation is more efficacious than pelvic floor muscle training exercises and behavioral therapy for improving: urgency, urinary incontinence episodes, daily voids, volume per void, and overall quality of life. Sacral neuromodulation is more efficacious than antimuscarinic treatment for subjective improvement of overactive bladder and quality of life. Transvaginal electrical stimulation demonstrates subjective improvement in overactive bladder symptoms and urodynamic parameters. Multiple therapies, including physical therapy, behavioral therapy, botulinum toxin A, acupuncture, magnetic stimulation, mirabegron, posterior tibial nerve stimulation, sacral neuromodulation, and transvaginal electrical stimulation, are efficacious in the treatment of overactive bladder. 

References

  1. Bosch JL, Weiss JP. The prevalence and causes of nocturia. J Urol. 2010 Aug;184(2):440-6.
  2. Cornu JN, Abrams P, Chapple CR, Dmochowski RR, Lemack GE, Michel MC, Tubaro A, Madersbacher S. A contemporary assessment of nocturia: definition, epidemiology, pathophysiology, and management--a systematic review and meta-analysis. Eur Urol. 2012 Nov;62(5):877-90.
  3. Hofmeester I, Kollen BJ, Steffens MG, Bosch JL, Drake MJ, Weiss JP, Blanker MH.
  4. The association between nocturia and nocturnal polyuria in clinical and epidemiological studies: a systematic review and meta-analyses. J Urol. 2014 Apr;191(4):1028-33.
  5. DmochowskicR, Wein AJ. Lower Urinary Tract Pharmacotherapy for Nocturia. Chapter 8 in: Nocturia , Causes, Consequences and Clinical Approaches, pp127-134, Springer 2012
  6. Yokoyama O, Homma Y, Yamaguchi O. Imidafenacin, an antimuscarinic agent, improves nocturia and reduces nocturnal urine volume. Urology. 2013 Sep;82(3):515-20
  7. Reynolds WS, McPheeters M, Blume J, Surawicz T, Worley K, Wang L, Hartmann K. Comparative Effectiveness of Anticholinergic Therapy for Overactive Bladder in Women: A Systematic Review and Meta-analysis. Obstet Gynecol. 2015 Jun;125(6):1423-32. 
  8. Olivera CK, Meriwether K, El-Nashar S, Grimes CL, Chen CC, Orejuela F, Antosh D, Gleason J, Kim-Fine S, Wheeler T, McFadden B, Balk EM, Murphy M; Systematic Review Group for the Society of Gynecological Surgeons. Nonantimuscarinic treatment for overactive bladder: a systematic review. Am J Obstet Gynecol. 2016 Jul;215(1):34-57.
  9. Peters KM, Macdiarmid SA, Wooldridge LS, Leong FC, Shobeiri SA, Rovner ES, Siegel SW, Tate SB, Jarnagin BK, Rosenblatt PL, Feagins BA. Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: results from the overactive bladder innovative therapy trial. J Urol. 2009 Sep;182(3):1055-61.
  10. Vecchioli-Scaldazza C, Morosetti C, Berouz A, Giannubilo W, Ferrara V. Solifenacin succinate versus percutaneous tibial nerve stimulation in women with overactive bladder syndrome: results of a randomized controlled crossover study. Gynecol Obstet Invest. 2013;75(4):230-4.
  11. Leong FC, McLennan MT, Barr SA, Steele AC. Posterior tibial nerve stimulation in patients who have failed anticholinergic therapy: efficacy and time to response. Female Pelvic Med Reconstr Surg. 2011 Mar;17(2):74-5.
  12. Moossdorff-Steinhauser HF, Berghmans B. Effects of percutaneous tibial nerve stimulation on adult patients with overactive bladder syndrome: a systematic review. Neurourol Urodyn. 2013 Mar;32(3):206-14.
  13. K-E Andersson, MD, PhD
  14. Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA, and Institute of Clinical Medicine, Department of Obstetrics and Gynecology, Aarhus University, Aarhus Denmark
     

Correspondence:

Institute of Clinical Medicine, Department of Obstetrics and Gynecology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK 8200 Aarhus N, Denmark.

tel +510-717-3765

e-mail: karl-erik.andersson@med.lu.se, kea@aias.au.dk

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