What medications are used to treat interstitial cystitis/bladder pain syndrome (IC/BPS)?

Medications for Interstitial Cystitis/Bladder Pain Syndrome

Treatment should begin with oral medications including amitriptyline, cimetidine, hydroxyzine, or pentosan polysulfate, combined with intravesical therapies such as dimethyl sulfoxide (DMSO), heparin, or lidocaine, using a multimodal approach rather than sequential monotherapy. 1

Treatment Framework

The 2022 AUA guidelines fundamentally changed the approach to IC/BPS treatment by eliminating the traditional first-through-sixth-line tier system. Instead, treatments are now categorized into behavioral/non-pharmacologic, oral medicines, bladder instillations, procedures, and major surgery, emphasizing that treatment must be tailored to individual patient characteristics and phenotypes. 1

Oral Medications

Amitriptyline (Evidence Strength: Grade B)

• Superior to placebo for improving IC/BPS symptoms but adverse events are common including sedation, drowsiness, and nausea. 1
• Start at 10 mg and titrate gradually to 75-100 mg if tolerated. 1
• Despite side effects that can compromise quality of life, these are not life-threatening. 1

Pentosan Polysulfate (Evidence Strength: Grade B)

• The only FDA-approved oral agent for IC/BPS and the most extensively studied medication. 1
• Evidence is contradictory—some trials show no difference from placebo while others demonstrate improvement. 1
• Critical warning: Patients must be counseled about potential macular damage and vision-related injuries before starting or continuing treatment. 1
• The FDA approved a new warning label in June 2020 requiring detailed ophthalmologic history before treatment, baseline retinal examination for patients with preexisting eye conditions, and retinal examination within six months of starting therapy with periodic monitoring. 1
• Maculopathy prevalence is related to cumulative PPS exposure and may be irreversible. 1

Cimetidine (Evidence Strength: Grade B)

• Shows clinically significant improvement in IC/BPS symptoms, pain, and nocturia with no adverse events reported. 1

Hydroxyzine (Evidence Strength: Grade C)

• Demonstrates clinically significant improvement compared to placebo. 1
• Patients with systemic allergies may be more likely to respond. 1
• Common but generally not serious adverse events include short-term sedation and weakness. 1

Intravesical Therapies

Dimethyl Sulfoxide (DMSO)

• FDA-approved specifically for symptomatic relief of interstitial cystitis. 2
• Patients may experience a garlic-like taste within minutes of instillation lasting several hours, with breath and skin odor persisting up to 72 hours. 2
• Some discomfort on administration is common but typically becomes less prominent with repeated treatments. 2
• Eye evaluations including slit lamp examinations should be performed prior to and periodically during treatment due to animal studies showing eye changes with large doses. 2

Heparin and Lidocaine

• May be administered as intravesical treatments with minor adverse events and unpredictable individual efficacy. 1

Pain Management Considerations

Pain management alone does not constitute sufficient treatment for IC/BPS—a multimodal approach combining pharmacologic agents with other therapies is most effective. 1

• Non-opioid alternatives should be used preferentially for pain management. 1
• Due to the global opioid crisis, chronic opioids should be used judiciously and only after informed shared decision-making with periodic follow-ups to assess efficacy, adverse events, compliance, and potential for abuse or misuse. 1
• Patients must also be treated for underlying bladder-related symptoms, not just pain. 1

Advanced Pharmacologic Options

Intradetrusor Botulinum Toxin A (Evidence Strength: Grade C)

• May be administered if other treatments have not provided adequate symptom control. 1
• The 100 U dose is appropriate based on substantial evidence showing reduced morbidity compared to higher doses. 1
• Patients must be willing to accept the possibility that intermittent self-catheterization may be necessary post-treatment. 1
• Should be administered by experienced practitioners and is relatively contraindicated for patients with impaired bladder emptying. 1

Cyclosporine A (Evidence Strength: Grade C)

• May be considered if other treatments have failed. 1, 3

Critical Treatment Principles

Concurrent, multimodal therapies may be offered rather than sequential monotherapy. 1 This represents a fundamental shift from earlier guidelines that recommended trying one treatment at a time.

Treatments that should NOT be offered include long-term oral antibiotic administration and intravesical BCG. 3

None of the pain medications discussed are specifically indicated for IC/BPS—they are used off-label based on their effectiveness in other chronic pain conditions. 1