What are the treatment options for interstitial cystitis refractory to histamine and amitriptyline (Elavil)?

Treatment of Interstitial Cystitis Refractory to Antihistamines and Amitriptyline

For patients with IC/BPS who have failed antihistamines and amitriptyline, advance to intravesical therapies with DMSO, heparin, and lidocaine as the next treatment tier, followed by cystoscopy with hydrodistension if intravesical treatments fail. 1, 2

Immediate Next Steps: Intravesical Therapies

The American Urological Association guidelines establish a clear treatment hierarchy where intravesical therapies represent the appropriate escalation after oral medication failure 1, 2:

DMSO (Dimethyl Sulfoxide) - FDA-Approved Option

• DMSO is the only FDA-approved intravesical treatment for IC/BPS and should be offered as a primary intravesical option 3
• Instill 50 mL of RIMSO-50 (50% DMSO solution) directly into the bladder via catheter, retain for 15 minutes, then allow spontaneous voiding 3
• Administer every 2 weeks until maximum symptomatic relief is obtained, then increase intervals between treatments 3
• Apply lidocaine jelly to the urethra before catheter insertion to prevent spasm 3
• Consider oral analgesics or belladonna/opium suppositories prior to instillation to reduce bladder spasm 3
• Critical caveat: Patients will experience a garlic-like taste within minutes that may last several hours, with breath and skin odor persisting up to 72 hours 3
• Obtain baseline and periodic slit lamp eye examinations, as animal studies showed ocular changes with prolonged high-dose DMSO 3

Heparin and Lidocaine Combination

• Intravesical heparin repairs the damaged glycosaminoglycan layer of the bladder and provides clinically significant symptom improvement 2, 4
• Lidocaine provides rapid-onset temporary relief of bladder pain 2
• These can be used concurrently with or following oral medications 2

Sodium Hyaluronate and Chondroitin Sulfate

• Consider intravesical solutions containing sodium hyaluronate or chondroitin sulfate to reduce bladder inflammation and replenish the glycosaminoglycan layer 4
• These agents showed promise in pilot trials, though large controlled studies are limited 4

Third-Line: Cystoscopy with Hydrodistension

If intravesical therapies fail after adequate trial:

• Perform cystoscopy to determine anatomic bladder capacity and identify fibrosis-related capacity reduction 2
• Avoid high-pressure (>80-100 cm H₂O) and long-duration (>10 minutes) hydrodistension due to increased risk of bladder rupture and sepsis without consistent benefit increase 1, 2
• If Hunner lesions are identified, perform fulguration and/or inject triamcinolone for significant symptom relief 2

Fourth-Line: Advanced Interventions for Truly Refractory Cases

Reserve these only after all above options have failed 1, 2:

Sacral Neuromodulation

• Has Grade C evidence with limited sample sizes and lack of durable follow-up 2
• Not FDA-approved for IC/BPS but may be considered in refractory cases 2

Cyclosporine A

• Has Grade C evidence and is not FDA-approved for IC/BPS 2
• Reserved for patients who have exhausted all other treatment options 2

Intradetrusor Botulinum Toxin A

• Has Grade C evidence and is not FDA-approved for IC/BPS 2
• Consider only after failure of all other therapies 2

Concurrent Pain Management Throughout Treatment

• Implement multimodal pain management approaches with non-opioid alternatives strongly preferred due to the chronic nature of IC/BPS and the global opioid crisis 1, 2
• Pain management alone does not constitute sufficient treatment—underlying bladder symptoms must be addressed simultaneously 1, 2
• Use judicious chronic opioids only after informed shared decision-making with periodic follow-ups to assess efficacy, adverse events, compliance, and potential for abuse 1

Interventional Pain Management Option

For patients with severe refractory pain despite the above measures:

• Pulsed radiofrequency (PRF) treatment of the superior hypogastric plexus may provide long-term pain relief (up to 2.5 years in case reports) 5
• This provides nondestructive neuromodulation to the plexus transmitting pain signals from pelvic viscera 5
• Perform diagnostic block first to predict response 5
• Apply radiofrequency pulses at 2 Hz frequency, 20 ms pulse width for 120 seconds twice per session, maintaining tissue temperature at 42°C 5

Critical Pitfalls to Avoid

• Do not offer: Long-term oral antibiotics, intravesical BCG, intravesical resiniferatoxin, high-pressure long-duration hydrodistension, or systemic long-term glucocorticoids 1, 2
• Do not prescribe pelvic floor strengthening exercises—only relaxation techniques should be used 2
• Do not abandon behavioral modifications (dietary management, stress management, heat/cold application) even when advancing to more invasive therapies 1, 2
• Treatment efficacy is unpredictable—multiple therapeutic options may need sequential trials before adequate symptom control is achieved 2

Documentation and Monitoring

• Document baseline and ongoing symptoms using validated tools such as the Interstitial Cystitis Symptom Index (ICSI, scores 0-20) to objectively measure treatment effects 6, 2
• Educate patients on the chronic nature of IC/BPS requiring long-term management 2