Clinical Review

When treating interstitial cystitis, address all sources of pain

OBG Manag. 2010 July;22(7):44-49

References

1. Perez-Marrero R, Emerson LE, Feltis JT. A controlled study of dimethyl sulfoxide in interstitial cystitis. J Urol. 1988;140(1):36-39.

2. Parsons CL, Benson G, Childs SJ, Hanno P, Sant GR, Webster G. A quantitatively controlled method to study prospectively interstitial cystitis and demonstrate the efficacy of pentosanpolysulfate. J Urol. 1993;150(3):845-848.

3. Mulholland SG, Hanno P, Parsons CL, Sant GR, Staskin DR. Pentosan polysulfate sodium for therapy of interstitial cystitis. A double-blind placebo-controlled clinical study. Urology. 1990;35(6):552-558.

4. Hanno PM. Analysis of long-term Elmiron therapy for interstitial cystitis. Urology. 1997;49(5A suppl):93-99.

5. Teichman JM, Nielsen-Omeis BJ. Potassium leak test predicts outcome in interstitial cystitis. J Urol. 1999;161(6):1791-1796.

6. Jepsen JV, Sall M, Rhodes PR, Schmidt D, Messing E, Bruskewitz RC. Long-term experience with pentosanpolysulfate in interstitial cystitis. Urology. 1998;51(3):381-387.

7. Bade JJ, Laseur M, Nieuwenburg A, van der Weele LT, Mensink HJ. A placebo-controlled study of intravesical pentosanpolysulphate for the treatment of interstitial cystitis. Br J Urol. 1997;79(2):168-171.

8. 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(2):533-536.

9. Weiss JM. Pelvic floor myofascial trigger points: manual therapy for interstitial cystitis and the urgency-frequency syndrome. J Urol. 2001;166(6):2226-2231.

10. FitzGerald MP, Anderson RU, Potts J, et al. Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes. J Urol. 2009;182(2):570-580.

11. Parsons CL. Successful downregulation of bladder sensory nerves with combination of heparin and alkalinized lidocaine in patients with interstitial cystitis. Urology. 2005;65(1):45-48.

12. Henry R, Patterson L, Avery N, et al. Absorption of alkalized intravesical lidocaine in normal and inflamed bladders: a simple method for improving bladder anesthesia. J Urol. 2001;165(6 Pt 1):1900-1903.

13. Theoharides TC, Sant GR. Hydroxyzine therapy for interstitial cystitis. Urology. 1997;49(supple 5A):108-110.

14. Sant GR, Propert KJ, Hanno PM, et al. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. J Urol. 2003;170(3):810-815.

15. Sasaki K, Smith CP, Chuang YC, Lee JY, Kim JC, Chancellor MB. Oral gabapentin (neurontin) treatment of refractory genitourinary tract pain. Tech Urol. 2001;7(1):47-49.

16. Lentz GM, Bavendam T, Stenchever MA, Miller JL, Smalldridge J. Hormonal manipulation in women with chronic, cyclic irritable bladder symptoms and pelvic pain. Am J Obstet Gynecol. 2002;186(6):1268-1273.

The one published randomized, clinical trial of DMSO showed marked improvement in symptoms in 53% of patients treated every 2 weeks for a total of eight treatments, compared with 18% of patients treated with placebo (number needed to treat [NNT], 2.8).¹

Oral PPS may ease symptoms—after several months of use

Pentosan polysulfate sodium (PPS) is a semi-synthetically produced heparin-like macro-molecular carbohydrate derivative, which chemically and structurally resembles glycosaminoglycans. In 1996, PPS became the first oral drug approved for the treatment of IC. It is sold under the brand name Elmiron. Its efficacy is thought to derive from its glycosaminoglycan-like characteristics, which act to restore integrity of the urothelial barrier. The recommended dosage is 100 mg three times daily. PPS is cleared in the urine.

Randomized, controlled trials of the efficacy of PPS have produced mixed results; at 3 months, however, it appears to produce a 25% to 50% response rate, compared with a placebo response rate of 13% to 23%, yielding a NNT of about 4.^2,3 Pelvic pain diminished in as many as 45% of patients, compared with about 18% in the placebo group.

Because of its mode of action, therapeutic response is delayed. The patient generally does not respond before about 3 months of treatment, but it can be as long as 12 months.⁴ In general, a 6-month trial should be completed before concluding that the patient is unresponsive to PPS. A positive PST may be predictive of response to PPS.⁵

PPS has low toxicity and few side effects. In rare cases, the transaminase level may rise. Headache, nausea, diarrhea, dizziness, skin rash, peripheral edema, and hair loss are the most common side effects, but they occur in fewer than 10% of patients.⁶ In randomized trials of PPS, in fact, adverse effects often occurred at a higher rate in the placebo group.³ No serious interactions between oral PPS and other medications have been reported.

Some data suggest that PPS may be effective when it is administered intravesically.⁷ This may be an option for patients who experience side effects after oral administration.

Among tricyclics, amitriptyline is most effective

Tricyclic antidepressants have proved to be effective in the treatment of IC, particularly amitriptyline, the most commonly prescribed tricyclic for the disease. Amitriptyline has multiple modes of action. Its anticholinergic effects reduce urinary frequency, and its sedating effects improve sleep and help decrease nocturia. Tricyclics effectively treat neuropathic pain—a mode of action that is probably important in IC.

The efficacy of amitriptyline has been confirmed in at least one randomized, double-blinded, placebo-controlled trial of 50 patients with IC.⁸ Mean symptom scores decreased by 31% among patients treated with amitriptyline, compared with 13% in the placebo-treated group. Pain scores diminished by 43% in the amitriptyline group, compared with a 2% increase in the placebo group. Among patients treated with amitriptyline, 53% rated their satisfaction “good” or “excellent,” compared with 4% in the placebo group, yielding a NNT of 2. Anticholinergic side effects, especially dry mouth, were reported by 92% of patients treated with amitriptyline, compared with 21% of those treated with placebo. Final dosages of amitriptyline in this study were:

25 mg in 29% of patients
50 mg in 37.5%
75 mg in 21%
100 mg in 12.5%.

Patients self-titrated, based on efficacy and side effects.

This clinical trial confirms the clinical impression that amitriptyline is effective and relatively well tolerated, and that dosages lower than those used for the treatment of depression are adequate for treatment of IC.

Physical therapy may be effective in intractable cases

The pelvic floor muscles can become a source of persistent pain even if bladder inflammation and up-regulation are aggressively treated. Treatment of any pelvic floor muscle dysfunction and hypertonus is an important component of management in patients who have IC. Physical therapy techniques that involve manual or soft-tissue manipulation can be used to improve symptoms moderately or markedly in as many as 83% of patients who have failed a more traditional approach to IC.⁹ A published clinical trial suggests that physical therapy is effective in the treatment of IC/PBS.¹⁰

Intravesical heparin has no effect on coagulation

Heparin is thought to repair the glycosaminoglycan layer of the bladder, or at least to coat and protect bladder epithelium. It can be used intravesically with minimal concern for anticoagulation. Because heparin is insignificantly absorbed into the circulation from the bladder, a partial thromboplastin time assay is not needed.

Heparin is usually instilled in combination with other medications—either dimethylsulfoxide or local anesthetic agents.

No randomized trials of intravesical heparin treatment hve been performed.