The generalist’s guide to interstitial cystitis

Urge suppression

Another helpful strategy is having the patient increase the time between voids using distraction techniques and by contracting the pelvic floor muscles and overriding the first urge to void.

Oral medications

Pentosan polysulfate sodium is a glycosaminoglycan with an affinity for mucosal membranes. It is approved by the Food and Drug Administration (FDA) for the treatment of interstitial cystitis. The mechanism by which it reduces pain and urinary frequency is unclear, but it may replace the deficient glycosaminoglycan layer in the bladder epithelium.

Pain relief occurs in approximately 40% to 60% of patients after 3 months of therapy (100 mg orally 3 times daily).¹⁵

The patient should clearly understand that beneficial effects may not occur for 3 to 6 months, and that patience is necessary to give the drug an adequate trial. The response is maintained over the long term, and the drug should be used indefinitely. Pentosan polysulfate sodium is well tolerated, although gastrointestinal side effects and reversible alopecia occur in 4% of patients.

Performing a cystoscopy under anesthesia with hydrodistension is not always necessary prior to starting pentosan polysulfate, as long as the patient is not at risk for bladder neoplasms. However, prior to starting the drug the minimal evaluation should include a voiding diary and either the PUF questionnaire or the potassium sensitivity test.

Antihistamines. If the patient has a history of allergies, or mast cells were confirmed on bladder biopsy, an antihistamine such as hydroxyzine should be given along with pentosan polysulfate sodium. Hydroxyzine has an inhibitory effect on bladder mast cells, as well as anticholinergic and analgesic properties, which improve typical symptoms of interstitial cystitis.

Initiate hydroxyzine at a dose of 10 to 25 mg at bedtime for 1 week, gradually increasing to 50 to 75 mg. Side effects include drowsiness, which is beneficial for women who have nocturia. Other effects are dry mouth and a bitter taste.

Amitriptyline hydrochloride also has analgesic, antihistaminic, anticholinergic, and sedative effects. Amitriptyline is a noradrenaline and serotonin reuptake inhibitor that blocks nociception in the central nervous system.

Compared with placebo, amitriptyline significantly improved symptom scores, pain, and urgency intensity. In a study by van Ophoven and colleagues,¹⁶ 50 patients (44 women, 6 men) were randomly assigned to amitriptyline at self-titrating doses or placebo. O’Leary-Sant symptom scores, pain, and urgency intensity improved significantly in the amitriptyline group, compared with placebo.

Anticholinergic side effects (eg, dry mouth, constipation), weight gain, and sedation occur in 20% to 80% of patients. In an open-label study of amitriptyline for interstitial cystitis,¹⁷ long-term efficacy (mean of 17 months) revealed a 64% response rate (60 of 94 patients) using the global response assessment questionnaire.

Start amitriptyline at a dose of 10 to 25 mg at bedtime, gradually increasing to 75 mg as tolerated. Sedation becomes a limiting factor in the higher doses. Other tricyclic antidepressants have not been studied to any significant extent in treating interstitial cystitis. When used as part of a multimodal treatment in addition to pentosan polysulfate sodium, amitriptyline may be tapered off once remission is attained. No studies have compared treatment response using pentosan polysulfate sodium with and without amitriptyline.

Calcium channel blockers (nifedipine) and drugs for neuropathic pain (gabapentin) are being investigated.

Anticholinergic and antispasmodic agents are typically ineffective in women with interstitial cystitis. In fact, if a patient has no improvement in her symptoms after these drugs are tried, interstitial cystitis should be strongly considered.

Oral L-arginine (1,500–3,000 mg per day, divided doses) improved symptoms in a small study by increasing nitric oxide synthase activity.¹⁸

NSAIDs are used adjunctively and may help reduce pain.

Intravesical therapy

Patients unable to tolerate oral medications may benefit from intravesical therapy. It can also be used as an adjunct to oral therapy. Intravesical therapy delivers drugs directly to the bladder wall with a low incidence of side effects. Risks include a potential for UTI via catheterization, as well as transient chemical cystitis, which exacerbates symptoms. A variety of therapeutic “cocktails” are used.

Dimethyl sulfoxide (DMSO) is the only other drug, besides pentosan polysulfate, approved by the FDA for treatment of interstitial cystitis. DMSO has antiinflammatory, analgesic, and muscle-relaxant effects, and inhibits mast-cell activity. DMSO induces remission in 50% to 70% of patients for up to 24 months.¹⁹

Lidocaine jelly is injected intraurethrally, followed by instillation of 50 cc of DMSO (alone or with heparin, sodium bicarbonate, and Solu-Cortef). This solution is held in the bladder for 20 to 30 minutes before voiding.

DMSO is secreted through the lungs and skin and has a garlic-like odor. Treatments are administered every 1 to 2 weeks for a total of 4 to 8 treatments. If the condition relapses, DMSO can be reinstituted on a long-term basis. Motivated patients can be taught to administer this treatment themselves.