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Quick Reference Guide for Clinicians
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Diagnosis and Management of Interstitial Cystitis/Painful Bladder Syndrome

(Published May 2008)

Oral Therapy

The majority of agents used in the treatment of IC/PBS are not approved by the Food and Drug Administration (FDA) for this indication. Oral pentosan polysulfate sodium (PPS) and intravesical dimethylsulfoxide (DMSO) are the only FDA-approved agents. The majority of medications mentioned in this Quick Reference Guide have either shown efficacy in non-FDA-based clinical trials or are used in clinical practice by advisory committee members.

Approach to therapy

  • The preferred approach to first-line therapy varies among clinicians, making construction of treatment algorithms for IC/PBS a challenge.
  • Most clinicians knowledgeable about IC/PBS focus on self-care and oral therapy, adding intravesical therapy as needed.
  • Surgery is an option of last resort for patients whose symptoms are unresponsive to primary forms of treatment, and is rarely performed.

Oral agents

  • Oral therapy is a mainstay of IC/PBS management.
  • The most commonly used oral agents (with the exception of use in clinical trials) are:1
    • Amitriptyline
    • Hydroxyzine
    • Pentosan polysulfate sodium
  • Other oral agents are sometimes used for symptomatic relief.


  • Tricyclic antidepressant often used to treat IC/PBS.
  • The dose used for IC/PBS is generally much lower than that used for depression.
  • Modulates pain by decreasing reuptake of serotonin and norepinephrine in the central nervous system.2
  • May help stabilize mast cells, reducing release of pro-inflammatory substances during allergic reactions.2
  • May increase bladder capacity through beta-adrenergic receptors on the bladder.3
  • Seems to be most effective for IC/PBS patients for whom pain is a significant component of their symptom complex.
  • A randomized, placebo-controlled trial (N=50) found that treatment significantly reduced mean symptom score compared with placebo (p = 0.005).4
  • Sedation can be a limiting side effect but can promote sleep if taken in the evening.
  • Should be prescribed only by health care providers who are familiar with its side effect profile and use in IC/PBS.
  • Typical doses of amitriptyline used for IC/PBS: start at 10 mg to 25 mg qhs; if needed, the dose can be slowly increased to 75 mg qhs, as tolerated.

Hydroxyzine (Atarax®, Vistaril®)

  • Histamine H1 antagonist.
  • Inhibits mast cell degranulation, thus reducing histamine release, which has been implicated in the pathophysiology of IC/PBS.1,2
  • Open-label study found treatment reduced symptom scores by 55 percent on average in patients who have a history of allergies.5
  • A subsequent randomized controlled trial found no reduction in global assessment scores compared with placebo.6
  • May promote sleep and may act as a skeletal muscle relaxant, two actions that may help modify IC/PBS symptoms.
  • Typical doses of hydroxyzine used for IC/PBS: started at 10 mg to 25 mg qhs; if needed, the dose can be slowly increased to 75 mg qhs, as tolerated.

Pentosan polysulfate sodium (PPS; Elmiron®)

  • The only oral therapy approved by the FDA for IC/PBS (1996).
  • PPS is a heparin analogue that has 1/15th the anticoagulation activity of heparin.2
  • PPS is believed to repair the lining of the bladder, counteracting the increased permeability seen in IC/PBS.2
  • In clinical trials, PPS was found to be beneficial in a minority of patients (overall improvement of greater than 25 percent in 32 percent of PPS-treated patients compared with 16 percent for placebo).7,8
  • A long-term, open-label study found that 42 percent to 62 percent of patients treated with PPS experienced moderate or better improvement in overall symptoms when the data are analyzed without the subjects who withdrew for lack of efficacy.9
  • Can take 2 months or longer to be effective.
  • Is generally well tolerated.
  • Side effects include dyspepsia and reversible alopecia.
  • Typical doses of PPS used for IC/PBS: 100 mg TID.

Other oral agents

  • Specialists occasionally use other oral agents to treat IC/PBS symptoms.
  • Clinical trial data are not available for these agents in treatment of IC/PBS.

Other oral agents used in IC/PBS management 1,2,11,12
Some clinicians use these agents to treat IC/PBS; like many agents used for IC/PBS, they are not FDA-approved for this use
Oral Agent Comment
Alpha blockers Examples: doxazosin, terazosin
Anticonvulsants Examples: gabapentin, pregabalin, carbamazepine. Some clinicians use these agents to treat IC/PBS; like many agents used for IC/PBS, they are not FDA-approved for this use
Antihistamines other than hydroxyzine Anecdotal reports exist of symptom improvement in some patients with loratadine or diphenhydramine
H2 antagonists Example: cimetidine
Leukotriene inhibitors Example: montelukast
Muscle relaxants Can be an effective therapy for muscle spasticity syndromes like pelvic floor dysfunction
Opioids Chronic narcotic therapy is sometimes used in patients who respond poorly to other therapies; referral for pain management can be helpful for some patients
Tricyclics other than amitriptyline Examples: imipramine, nortriptyline, doxepin
Urinary anesthetics Example: phenazopyridine


  1. Hanno PM. Painful bladder syndrome (interstitial cystitis). In: Hanno PM, Wein AJ, Malkowicz SB, editors. Penn Clinical Manual of Urology. Philadelphia: Saunders; 2007. p. 217-34.
  2. Moldwin RM, Sant GR. Interstitial cystitis: a pathophysiology and treatment update. Clin Obstet Gynecol. 2002;45:p. 259-72.
  3. Hanno PM. Painful bladder syndrome/interstitial cystitis and related disorders. In: Wein AJ, editor. Campbell-Walsh Urology. 9th edition. Philadelphia: Saunders; 2007. p. 330-370.
  4. van Ophoven A, Pokupic S, Heinecke A, Hertle L. A prospective, randomized, placebo controlled, double-blind study of amitriptyline for the treatment of interstitial cystitis. J Urol. 2004;172:533-6.
  5. Theoharides TC, Sant GC. Hydroxyzine therapy for interstitial cystitis. Urology. 1997;49:108-10.
  6. Sant GR, Propert KJ, Hanno PM. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. J Urol. 2003;170(3):810-15.
  7. Parsons CL, Benson Parsons CL, Benson G, Childs SJ, Hanno PM, Sant GR, et al. A quantitatively controlled method to study prospectively interstitial cystitis and demonstrate the efficacy of pentosanpolysulfate. J Urol. 1993;150(3):845-8.
  8. Mulholland SG, Hanno PM, Parsons CL, Sant GR, Staskin DR. Pentosan polysulfate sodium for therapy of interstitial cystitis. Urology. 1990;35(6):552-8.
  9. Hanno PM. Analysis of long-term Elmiron therapy for interstitial cystitis. Urology. 1997;49(Suppl 5A):93-9.
  10. Chancellor M, Yoshimura N. Treatment of interstitial cystitis. Urology. 2004;63(Suppl A):85-92.
  11. Moldwin RM, Evans RJ, Stanford EJ, Rosenberg MT. Rational approaches to the treatment of patients with interstitial cystitis. Urology. 2007;69(Suppl 4A):73-81.
  12. Nickel JC, Berger R, Pontari M. Changing paradigms for chronic pelvic pain: a report from the Chronic Pelvic Pain/Chronic Prostatitis Scientific Workshop, October 1921, 2005, Baltimore, MD. Rev Urol. 2006;8(1):28-35.