Treatment

• Treatment Philosophy
  • The ultimate goal in the treatment of disease is to neutralize the factor or factors responsible for the disorder. As long as the cause is unknown, treatments will be based on empiricism. Although the symptoms of interstitial cystitis can be controlled with one of a variety of treatments in the overwhelming majority of patients, there is little evidence that treatment accomplishes anything more than influencing the symptomatic expression of the disease rather than curing the condition. In order that the best therapeutic results for an individual patient are achieved, both patient and physician must understand that there is no sure cure for IC, nor is there a single treatment that is effective in reducing symptoms for every patient. Most patients, however, can in fact benefit from one treatment or another or a combination of treatments and most can be maintained in a satisfied, although definitely not asymptomatic, state, punctuated by exacerbations and remissions.
• Initial treatment approach
  • Hydrodistention of the bladder under anesthesia, while technically a surgical treatment, is often the first therapeutic modality employed, often as a part of the diagnostic evaluation.
  • Once the diagnosis has been made, with or without hydrodistention, one must decide whether to institute therapy or employ a policy of conservative "watchful waiting". If the patient's symptoms are livable, the withholding of immediate treatment is reasonable.
    • While the concept of "livable" is certainly patient dependent, someone who gets up once or twice a night and voids every 2-3 hours during the day with minimal pain would certainly fall into this category
    • Patient education and empowerment: The Interstitial Cystitis Association is an important resource for information and support for patients as well as a clearing house for ideas and funding for researchers and clinicians.
  • There is data that timed voiding and behavioral therapy can be helpful in the short-term, especially in patients where frequency rather than pain predominates
  • Stress reduction, exercise, warm tub baths, and efforts by the patient to maintain a normal lifestyle all contribute to overall quality of life
  • Elaborate dietary restrictions are unsupported by any literature, but many patients do find their symptoms are adversely affected by specific foods and would do well to avoid them
    • Often this includes caffeine, alcohol, tomato-based foods, and beverages that might acidify the urine like cranberry juice
• Medical therapy
  • Tricyclic antidepressants
    • Amitriptyline
    • 10mg hs increasing over 5 weeks to 50mg hs
    • Maximum dose 75-100mg
    • Analgesic, antihistaminic, sedative properties
    • One-third of patients cannot tolerate due to tricyclic antidepressant side effects (especially sedation)
  • Antihistamines
    • Hydroxyzine
      • The unique piperazine H1-receptor antagonist hydroxyzine can block neuronal activation of mast cells
      • 25mg before bed increasing over 2 weeks (if sedation not a problem) to 50mg at night and 25mg in the morning
  • Sodium pentosanpolysulfate
    • A heparin analogue available in an oral formulation, 3-6% of which is excreted into the urine. It is sold under the trade name Elmiron.
    • The only oral agent approved for the treatment of the pain associated with interstitial cystitis, it is a sulfated mucopolysaccharide intended to remedy the purported defect in the epithelial permeability barrier, the glycosaminoglycan (GAG) layer, that may contribute to the pathogenesis of IC.
    • Given at a dose of 100mg three times daily, improvement is noted in about 35% of patients within 6 months. Side effects include a 4% chance of reversible hair loss, gastrointestinal upset and allergic rashes in some patients.
  • Analgesics
    • The long-term, appropriate use of pain medications forms an integral part of the treatment of a chronic pain condition like interstitial cystitis. Most patients can be helped markedly with medical pain management using pain medications commonly used for chronic neuropathic pain syndromes including antidepressants, anticonvulsants, and opioids.
• Intravesical therapy
  • Older rarely used therapies
    • Silver nitrate
    • Intravesical Clorpactin WCS 90
  • Dimethylsulfoxide (DMSO)
    • A product of the wood pulp industry and a derivative of lignin, DMSO has exceptional solvent properties and is freely miscible with water, lipids, and organic agents. Pharmacologic properties include membrane penetration, enhanced drug absorption, anti-inflammatory, analgesic, collagen dissolution, muscle relaxant, and mast cell histamine-release.
    • Approved for use in IC, it is generally given weekly for six weeks intravesically via catheter as 50cc of a 50% solution of DMSO (Rimso-50). A garlic odor is the predominant side effect. Success rates of 60-80% have been reported, though duration of effect is generally less than 6 months.
  • Exogenous glycoaminoglycans
    • Heparin
    • Sodium pentosanpolysulfate
  • BCG
    • Results of a National Institutes of Health trial instilling intravesical bacillus Calmette-Guerin on a weekly basis for 6 weeks should be available in early 2004.
  • Resiniferatoxin
    • A specific neurotoxin that desensitizes C fiber afferent neurons. Clinical trials in bladder pain, urgency/frequency are underway.
• Nerve Stimulation
  • Transcutaneous electrical nerve stimulation (TENS)
  • Acupuncture
  • Direct sacral nerve stimulation
    • Trial stimulation is performed with a percutaneous temporary electrode for a 3 to 4 day temporary stimulation period to access efficacy. The S3 nerve is most frequently used. A wire electrode is inserted into the foramen and connected to an external pulse generator (Medtronic Inc., Minneapolis, Minnesota, USA).
    • If the trial is successful, the patient can be considered for implantation of a permanent neural prosthesis. Neuromodulation has been shown to be effective in treating refractory urinary urge incontinence. Studies on therapeutic potential for interstitial cystitis are underway.
• Surgical therapy
  • Transurethral resection of a Hunner's ulcer
    • By electro-cautery or laser therapy, local destruction of a Hunner's ulcer can improve symptoms for 6-12 months in some patients.
  • Major surgical procedures for the therapy of interstitial cystitis provide options after all trials of conservative treatment have failed.
  • Supratrigonal cystectomy and the formation of an enterovesical anastomosis with bowel segments
  • Urinary diversion
    • With continent diversion
    • With ileal conduit
    • With cystectomy and orthotopic neobladder or Indiana pouch
    • Beware of development of pain in pouch or neobladder
  • 50% overall success rate of major surgery in literature as pain may persist or reoccur months or years after surgery.
• Strategy for management
  • As a rule, in the patient who does not respond to the initial diagnostic distention, and self-help protocols, oral therapy with amitriptyline or hydroxyzine is a noninvasive way to begin treatment. Patients who fail to demonstrate a satisfactory response in 6-10 weeks can be started on oral sodium pentosanpolysulfate. The antihistamine or tricyclic antidepressant can be discontinued if no response was noted, or continued if some limited efficacy was perceived. Sodium pentosanpolysulfate can be expected to be beneficial in one-third of patients. If no response is noted in 6-9 months, there is no point in continuing it.
  • Intravesical therapies are an important second-line strategy. A consultation with a pain center and consideration of analgesic treatment should be considered before a major surgical procedure is entertained.

References