GENERAL APPROACH TO TREATMENT

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• AUA 2011 Guidelines for interstitial cystitis/bladder pain syndrome
  The American Urological Association (AUA) announced its first guideline for the condition the AUA now refers to as interstitial cystitis/bladder pain syndrome (IC/BPS).

• What is the most effective treatment of interstitial cystitis?
  Onwude JL. BMJ 2008 Nov 27;337:a2325. doi: 10.1136/bmj.a2325 
  • a review

• Pharmacologic management of painful bladder syndrome/interstitial cystitis: a systematic review.
  Dimitrakov J, Kroenke K, Steer WD, et al. Arch Intern Med 2007;167:1922-9

• Rational approaches to the treatment of patients with interstitial cystitis. 
  Moldwin RM, Evans RJ, Stanford EJ, Rosenberg MT. Urology 2007;69(4 Suppl):73-81.

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​ORAL TREATMENT | Double-blind randomized placebo-controlled studies

 

• Safety and Efficacy of the Use of Intravesical and Oral Pentosan Polysulfate Sodium for Interstitial Cystitis: A Randomized Double-Blind Clinical Trial. 
  Davis EL, El Khoudary SR, Talbott EO, et al. J Urol 2007 Nov 12; [Epub ahead of print]

• A prospective, randomized, placebo controlled, double-blind study of amitriptyline for the treatment of interstitial cystitis. 
  van Ophoven A, Pokupic S, Heinecke A, et al. J Urol 2004;172:533-6
  • the authors conclude that amitriptyline therapy for 4 months is safe and effective for treating IC 
  • a statistically significant change in the symptom score and statistically significant improvement of pain and urgency intensity compared with placebo were observed
  • anticholinergic side effects constitute the major drawback of amitriptyline treatment for IC

• see also: 
  Efficacy of tricyclic antidepressant is associated with beta2-adrenoceptor genotype in patients with interstitial cystitis. 
  Nishijima S, Sugaya K, Yamada T, et al. Biomed Res 2006;27:163-7 
  • the efficay of imipramine was studied in 55 IC patients and 113 controls in relation to the polymorphism of the beta2-adrenoreceptor (ADRB2)
  • the results suggest that the Arg16Gly polymorphism of ADRB2 is related to down-regulation of ADRB2 expression in the detrusor muscle and that the response of IC to tricyclic antidepressant therapy depends on the Arg16Gly polymorphism.

• Randomized, double-blind, dose-ranging study of pentosan polysulfate sodium for interstitial cystitis. 
  Nickel JC, Barkin J, Forrest J, et al. Urology 2005;65:654-8
  • three dosages (300, 600, and 900 mg) of PPS in a randomized, double-blind, double-dummy, parallel-group, multicenter, 32-week study were studied in 380 IC patients
  • at study end, 27.5%, 56.9%, and 15.7% reported mild, moderate, and severe symptoms, respectively
  • for all three dosages of PPS, a clinically significant but similar response was demonstrated; the duration of therapy appears to be more important than the dosage

• Pilot study of sequential oral antibiotics for the treatment of interstitial cystitis. 
  Warren JW, Horne LM, Hebel JR, et al. J Urol 2000;163:1685-8
  • 50 patients with IC were randomized to receive 18 weeks of placebo or antibiotics, including rifampin plus a sequence of doxycycline, erythromycin, metronidazole, clindamycin, amoxicillin and ciprofloxacin for 3 weeks each. 
  • 12 of 25 patients (48%) in the antibiotic and 6 of 25 (24%) in the placebo group reported overall improvement (p = 0.14), while 10 and 5, respectively, noticed improvement in pain and urgency (p = 0.22). 
  • in the antibiotic group 20 participants (80%) had adverse effects compared with 10 (40%) in the placebo group (p = 0.009). 
  • the authors conclude that their findings suggest that these antibiotics alone or in combination may sometimes be associated with decreased symptoms in some patients but they do not represent a major advance in therapy for interstitial cystitis

• A randomized double-blind placebo-controlled crossover trial of the efficacy of L-arginine in the treatment of interstitial cystitis. 
  Cartledge JJ, Davies AM, Eardley I. BJU Int 2000;85:421-6 
  • the authors conclude that oral L-arginine produces a statistically significant improvement in the IC symptom index in patients with IC, but the effect is small; this effect may not be clinically significant as there were no improvements in the other variables assessed and no significant difference between the response to L-arginine and placebo
  • from these results the use of L-arginine cannot be recommended for treating IC

• A prospective double-blind clinically controlled multicenter trial of sodium pentosanpolysulfate in the treatment of interstitial cystitis and related painful bladder disease. 
  Holm-Bentzen M, Jacobsen F, Nerstrom B, et al. J Urol 1987;138:503-7 
  • protocol A included 43 patients with clinically and pathologically anatomically verified interstitial cystitis (28 or more mast cells per mm.2) 
  • protocol B included 72 patients with a painful bladder and unspecific histological findings 
  • patients were randomized to receive either sodium pentosanpolysulfate (200 mg. twice daily) or placebo capsules for 4 months 
  • before and after the trial the patients were evaluated with symptom grading, urodynamics and cystoscopy with distension and deep bladder biopsies 
  • the results showed no difference between the pre-trial and post-trial values in the sodium pentosanpolysulfate and placebo groups in both protocols in regard to symptoms, urodynamic parameters, cystoscopic appearance and mast cell counts. 
  • a significant increase in the cystoscopically determined bladder capacity in the sodium pentosanpolysulfate group in protocol A was found 
  • the authors conclude that no statistically or clinically significant effect of sodium pentosanpolysulfate was found compared to placebo in patients with painful bladder disease

 

Open studies and non-placebo-controlled studies

 

• Treatment of refractory interstitial cystitis/painful bladder syndrome with CystoProtek - an oral multi-agent natural supplement.
  Theoharides TC, Kempuraj D, Vakali S, Sant GR. Can J Urol 2008;15:4410-4
  • the authors conclude from this open-label, uncontrolled study with 250 refractory (male and female) IC/PBS patients that prospective randomized trials of such dietary supplements are warranted and that food supplements targeting the bladder GAGs may be a useful addition to the treatment arsenal

• Time to Initiation of Pentosan Polysulfate Sodium Treatment After Interstitial Cystitis Diagnosis: Effect on Symptom Improvement.
  Nickel JC, Kaufman DM, Zhang HF, et al. Urology 2008;71:57-61 
  • this is a retrospective analysis in patients in patients who had been treated with PPS 300 mg/day for 32 weeks in a multi-center, randomized, double-blind, parallel-group clinical trial 
  • initiation of PPS treatment within 6 months of establishing the diagnosis of IC may be associated with greater improvement in patient symptoms and symptom bother than treatment initiation 24 months or more after IC diagnosis

• The dual serotonin and noradrenaline reuptake inhibitor duloxetine for the treatment of interstitial cystitis: results of an observatinal study.
  van Ophoven A, Hertle L. J Urol 2007;177:552-5
  • in this observational study, duloxetine was given for two months to 48 women with IC according to the NIDDK criteria 
  • 5 patients (10.4%) responded and 17 (35.4%) dropped out due to nausea as a side effect
  • patients who responded reported onset of improvement but not until they had reached the target dose of 2x 40 mg per day
  • the authors conclude that duloxetine did not result in significant improvement of symptoms in patients with IC

• Cyclosporine A and pentosan polysulfate sodium for the treatment of interstitial cystitis: a randomized comparative study.
  Sairanen J, Tammela TL, Leppilahti M, et al. J Urol 2005;174:2235-8
  • in this prospective randomized - but not double blind - study, it was found that the clinical response rate was 75% for cyclosporine A compared to 19% for pentosan.

• Long-term results of amitriptyline treatment for interstitial cystitis.van Ophoven A, Hertle L. J Urol 2005;174:1837-40 
  • the authors conclude that long-term administration of amitriptyline is a safe and effective treatment for IC, provided that the drug is used judiciously to minimize adverse effects

• Safety and efficacy of concurrent application of oral pentosan polysulfate and subcutaneous low-dose heparin for patients with interstitial cystitis.
  van Ophoven A, Heinecke A, Hertle L. Urology 2005;66:707-11
  • the authors conclude that the concurrent administration of low-dose heparin and oral PPS appears to be a safe and efficacious treatment modality.

• Randomized, double-blind, dose-ranging study of pentosan polysulfate sodium for interstitial cystitis. 
  Nickel JC, Barkin J, Forrest J, et al. (Elmiron Study Group). Urology 2005;65:654-8
  • for all three dosages of oral PPS (300, 600, and 900 mg), a clinically significant but similar response was demonstrated
  • the duration of therapy appears to be more important than the dosage
  • a limitation of this study is the lack of a placebo group

• Efficacy of prednisone for severe refractory ulcerative interstitial cystitis.
  Soucy F, Grégoire M. J Urol 2005;173:841-3

• Long-term outcome of patients with interstitial cystitis treated with low dose cyclosporine A.
  Sairanen J, Forsell T, Ruutu M. J Urol 2004;171:2138-41. 
  • the initial cyclosporine dose: 3 mg/kg divided into 2 daily dosages; this was an open trial, a randomized trial is now being performed

• A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis
  Sant GR, Propert KJ, Hanno PM, et al. J Urol 2003;170:810-5

• The cysteinyl leukotriene D4 receptor antagonist montelukast for the treatment of interstitial cystitis. 
  Bouchelouche K, Nordling J, Hald T, Bouchelouche P. J Urol 2001;166:1734-7 
  • montelukast treatment resulted in significant improvement in urinary frequency and pain 
  • its efficacy for decreasing urinary frequency and pain imply a role of leukotriene receptor antagonists for managing interstitial cystitis but further placebo controlled clinical studies are needed

• Cimetidine in painful bladder syndrome: a histopathological study. 
  Dasgupta P, Sharma SD, Womack C, et al. BJU Int 2001;88:183-6

• Cimetidine in the treatment of interstitial cystitis. 
  Seshadri P, Emerson L, Morales A. Urology 1994;44:614-6

 

Case Reports

 

• Is interstitial cystitis an allergic disorder?: A case of interstitial cystitis treated successfully with anti-IgE.
  Lee J, Doggweiler-Wiygul R, Kim S, et al. Int J Urol 2006;13:631-4

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INTRAVESICAL TREATMENT

 

• Treatment of interstitial cystitis with Cystistat: a hyaluronic acid product. 
  Kallestrup EB, Jorgensen SS, Nordling J, Hald T. Scand J Urol Nephrol 2005;39:143-7 
  • in this prospective, unblinded, uncontrolled pilot study, 20 patients with IC/PBS received weekly bladder instillations of hyaluronic acid for 1 month and monthly instillations for a further 2 months
  • patients were then offered further monthly instillations and all were subsequently evaluated after 3 years 
  • patient outcomes assessed were urinary frequency, use of analgesics and pain 
  • the authors conclude that hyaluronic acid safely reduced the pain and, to lesser degree, the urinary frequency associated with IC

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Case Reports

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• [Intravesical instillation of resiniferatoxin for the patients with interstitial cystitis] [article in Japanese] 
  Takahashi S, Yanase M, Inoue R, et al. Hinyokika Kiyo 2006;52:911-3 
  • resiniferatoxin (RTX) treatment was given to 3 patients with incomplete improvement after hydrodistention; all 3 patients were free of bladder pain posttreatment and had slight improvement of the maximum voided volume
  • the authors conclude that although RTX treatment required general anaesthesia against severe bladder pain it is effective for selected IC patients

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Reviews

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• Resiniferatoxin in the treatment of interstitial cystitis: a systematic review.
  Mourtzoukou EG, Iavazzo C, Falagas ME. Int Urogynecol J Pelvic Floor Dysfunct 2008 Jun 19 [Epub ahead of print] 
  • the authors conclude that the effectiveness of resiniferatoxin in the treatment of interstitial cystitis remains unknown

• Pharmacologic management of painful bladder syndrome/interstitial cystitis: a systematic review.
  Dimitrakov J, Kroenke K, Steer WD, et al. Arch Intern Med 20078;167:1922-9

• Intravesical treatments for painful bladder syndrome/ interstitial cystitis. 
  Dawson T, Jamison J. Cochrane Database Syst Rev 2007 Oct 17;(4):CD006113
  • the authors conclude that the evidence base for treating PBS/IC using intravesical preparations is limited
  • the quality of trial reports was mixed and in some cases this precluded any meaningful data extraction 
  • BCG and oxybutin are reasonably well-tolerated and evidence is most promising for these 
  • resiniferatoxin showed no evidence of effect for most outcomes and caused pain, which reduced treatment compliance 
  • there is little evidence for the other treatments included in this review

• Hyaluronic Acid: An Effective Alternative Treatment of Interstitial Cystitis, Recurrent Urinary Tract Infections, and Hemorrhagic Cystitis? 
  Iavazzo C, Athanasiou S, Pitsouni E, Falagas ME. Eur Urol. 2007 Mar 20; [Epub ahead of print] 
  • a literature review on treatment of interstitial cystitis, hemorrhagic cystitis, and recurrent urinary tract infections with hyaluronic acid; the authors conclude that the available clinical data regarding the effectiveness of hyaluronic acid as a potential treatment of cystitis patients are limited and that there is a need for randomized controlled trials
  see also: editorial comment

• Recent developments of intravesical therapy of painful bladder syndrome/interstitial cystitis: a review. 
  Toft BR, Nordling J. Curr Opin Urol 2006;16:268-72

• Efficacy of interstitial cystitis treatments: a review. 
  Karsenty G, AlTaweel W, Hajebrahimi S, Corcos J. EAU-EBU Update Series 2006;4:47-61 
  • in this article, the degree of evidence regarding the clinical efficacy of available interstitial cystitis treatment options is reviewed
  • only three therapies are supported by a high level of evidence: oral cimetidine and amitriptyline and the intravesical dimethylsulfoxide (DMSO)

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NEUROMODULATION TREATMENT

• Reprogramming Requirements After Sacral Nerve Stimulator Implantation: Correlation With Preoperative Indication. 
  Maxwell KM, Clemens JQ, Mazzenga L, Kielb SJ. J Urol 2007 Dec 11 [Epub ahead of print]

• Bilateral s3 stimulator in patients with interstitial cystitis. 
  Steinberg AC, Oyama IA, Whitmore KE. Urology 2007;69:441-3
  • this retrospective study demonstrated that 15 patients diagnosed with interstitial cystitis with the symptoms of frequency, urgency, and pain had a significant decrease in frequency and nocturia with bilateral stimulator placement

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SURGICAL TREATMENT (UNDER CONSTRUCTION)

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OTHER TREATMENT

Hyperbaric oxygen

• Safety and efficacy of hyperbaric oxygen therapy for the treatment of interstitial cystitis: a randomized, sham controlled, double-blind trial. 
  van Ophoven A, Rossbach G, Pajonk F, Hertle L. J Urol 2006;176:1442-6 
  • the authors conclude that 3 out of 14 patients improved on hyperbaric oxygen therapy, and 0 out of 7 on "placebo"; the treatment with hyperbaric oxygenation appeared to be a safe

 

Hydrodistension

• Prolonged hydrodistention of the bladder for symptomatic treatment of interstitial cystitis: efficacy at 6 months and 1 year. 
  Glemain P, Riviere C, Lenormand L, et al. Eur Urol 2002;41:79-84
  • the authors conclude that prolonged hydrodistension showed a good but transient efficacy in the least developed or least severe forms of IC 

 

OVERVIEW OF RANDOMIZED-CONTROLLED TRIALS WITH BENEFICIAL EFFECT

​

Oral treatment

• A prospective, randomized, placebo controlled, double-blind study of amitriptyline for the treatment of interstitial cystitis. 
  van Ophoven A, Pokupic S, Heinecke A, et al. J Urol 2004;172:533-6
  • the authors conclude that amitriptyline therapy for 4 months is safe and effective for treating IC 
  • a statistically significant change in the symptom score and statistically significant improvement of pain and urgency intensity compared with placebo were observed
  • anticholinergic side effects constitute the major drawback of amitriptyline treatment for IC

• see also: 
  Efficacy of tricyclic antidepressant is associated with beta2-adrenoceptor genotype in patients with interstitial cystitis. 
  Nishijima S, Sugaya K, Yamada T, et al. Biomed Res 2006;27:163-7 
  • the efficay of imipramine was studied in 55 IC patients and 113 controls in relation to the polymorphism of the beta2-adrenoreceptor (ADRB2)
  • the results suggest that the Arg16Gly polymorphism of ADRB2 is related to down-regulation of ADRB2 expression in the detrusor muscle and that the response of IC to tricyclic antidepressant therapy depends on the Arg16Gly polymorphism.

• Randomized, double-blind, dose-ranging study of pentosan polysulfate sodium for interstitial cystitis. 
  Nickel JC, Barkin J, Forrest J, et al. Urology 2005;65:654-8
  • three dosages (300, 600, and 900 mg) of PPS in a randomized, double-blind, double-dummy, parallel-group, multicenter, 32-week study were studied in 380 IC patients
  • at study end, 27.5%, 56.9%, and 15.7% reported mild, moderate, and severe symptoms, respectively
  • for all three dosages of PPS, a clinically significant but similar response was demonstrated; the duration of therapy appears to be more important than the dosage

 

Intravesical treatment

• Time to Initiation of Pentosan Polysulfate Sodium Treatment After Interstitial Cystitis Diagnosis: Effect on Symptom Improvement.
  Nickel JC, Kaufman DM, Zhang HF, et al. Urology 2008;71:57-61 
  • this is a retrospective analysis in patients in patients who had been treated with PPS 300 mg/day for 32 weeks in a multi-center, randomized, double-blind, parallel-group clinical trial 
  • initiation of PPS treatment within 6 months of establishing the diagnosis of IC may be associated with greater improvement in patient symptoms and symptom bother than treatment initiation 24 months or more after IC diagnosis

• Safety and Efficacy of the Use of Intravesical and Oral Pentosan Polysulfate Sodium for Interstitial Cystitis: A Randomized Double-Blind Clinical Trial. 
  Davis EL, El Khoudary SR, Talbott EO, et al. J Urol 2007 Nov 12; [Epub ahead of print]
  • 41 females diagnosed with IC were randomized to receive a combination of intravesical pentosan polysulfate sodium plus oral pentosan polysulfate sodium or intravesical placebo plus oral pentosan polysulfate sodium for 6 weeks; all subjects continued to receive oral pentosan polysulfate sodium for another 12 weeks
  • at week 18 the treatment group showed statistically significant improvement in all quality of life scores, while the placebo group showed significant improvement in only 3 quality of life scores compared to the baseline