What are the gold standard treatments for interstitial cystitis?

Gold Standard Treatments for Interstitial Cystitis/Bladder Pain Syndrome

The gold standard approach begins with behavioral modifications and self-care practices for all patients, followed by oral amitriptyline or pentosan polysulfate as second-line therapy, with intravesical treatments reserved for inadequate responders—this stepwise escalation is mandated by the 2022 American Urological Association guidelines. 1

First-Line: Behavioral Modifications (Required for All Patients)

All patients must start with conservative measures before any pharmacologic intervention. 1, 2

Dietary Management

• Eliminate known bladder irritants including coffee, citrus products, and spicy foods 3, 2
• Implement an elimination diet to identify personal trigger foods that worsen symptoms 1, 3
• Alter urine concentration through strategic fluid management—either restrict fluids to concentrate urine less frequently or increase hydration to dilute irritants 1, 3

Physical Interventions

• Apply local heat or cold over the bladder or perineum for symptomatic pain relief 1, 3
• Perform pelvic floor muscle relaxation exercises only—never strengthening exercises, as these worsen symptoms 1, 2
• Consider bladder training with urge suppression techniques 1, 3

Stress Management

• Implement stress management practices such as meditation and imagery to manage stress-induced symptom exacerbations 1, 3

Over-the-Counter Options

• Consider quercetin, calcium glycerophosphates, or phenazopyridine for symptom relief 3, 4

Second-Line: Oral Medications

When behavioral modifications prove insufficient after an adequate trial, advance to oral pharmacotherapy. 2

Amitriptyline (Grade B Evidence)

• Start at 10 mg daily and titrate up to 100 mg per day as tolerated 1, 3
• Superior to placebo for symptom improvement with Grade B evidence strength 1, 3
• Common adverse effects include sedation, drowsiness, and nausea—these are not life-threatening but can compromise quality of life 1
• Begin at low doses to minimize side effects 1

Pentosan Polysulfate Sodium (FDA-Approved)

• The only FDA-approved oral medication for IC/BPS at 100 mg three times daily 3, 2, 5
• In clinical trials, 38% of patients showed >50% improvement in bladder pain versus 18% with placebo (p=0.005) 5
• Mandatory ophthalmologic monitoring is required due to risk of macular damage and ocular toxicity—this is a critical safety consideration 2, 6
• Maximum benefit may not occur until 3-6 months of treatment 5

Alternative Second-Line Oral Options

• Hydroxyzine and cimetidine are equally appropriate second-line options with no hierarchy among oral medications 6, 7
• These have Grade B or C evidence with minor adverse events 6

Second-Line: Intravesical Therapies

Intravesical treatments can be used concurrently with or following oral medications. 2

Dimethyl Sulfoxide (DMSO)

• Instill 50 mL directly into the bladder for 15 minutes, repeated every two weeks until maximum symptomatic relief is obtained 3, 8
• Apply analgesic lubricant gel (lidocaine jelly) to the urethra prior to catheter insertion to avoid spasm 8
• Patients will experience a garlic-like taste within minutes that may last several hours, with breath and skin odor persisting up to 72 hours 8
• For severe cases with very sensitive bladders, initial treatments should be done under anesthesia 8

Heparin

• Repairs the damaged glycosaminoglycan (GAG) layer of the bladder 3, 2
• Provides clinically significant symptom improvement 3, 2

Lidocaine

• Provides rapid onset temporary relief of bladder pain 3, 2
• Can be combined with other intravesical agents 7

Third-Line: Cystoscopy with Hydrodistension

• Perform cystoscopy when second-line treatments fail to determine anatomic bladder capacity and identify fibrosis-related capacity reduction 2, 6
• Avoid high-pressure (>80-100 cm H2O) and long-duration (>10 minutes) hydrodistension due to increased risk of bladder rupture and sepsis without consistent increase in benefit 1, 2

Fourth-Line: Treatment of Hunner Lesions (If Present)

• If Hunner lesions are identified on cystoscopy, perform fulguration (with laser or electrocautery) and/or injection of triamcinolone 3, 2
• Hunner lesions become easier to identify after distention when cracking and mucosal bleeding become evident 3
• This provides significant symptom relief for this specific IC/BPS subtype 3, 2

Fifth-Line: Advanced Interventions for Refractory Cases

Reserve these only for patients who have failed all other treatments. 2, 6

Sacral Neuromodulation

• Consider if other treatments have not provided adequate symptom control 3, 6
• Has Grade C evidence with limited sample sizes and lack of durable follow-up 2
• Not FDA-approved for IC/BPS 2

Cyclosporine A

• Administer orally for refractory cases 3, 6
• Has Grade C evidence and is not FDA-approved for IC/BPS 2

Intradetrusor Botulinum Toxin A

• May be beneficial but patients must accept the possibility of needing intermittent self-catheterization 3, 6
• Has Grade C evidence and is not FDA-approved for IC/BPS 2

Pain Management Throughout All Treatment Phases

Multimodal pain management approaches should be initiated and maintained throughout treatment, with non-opioid alternatives strongly preferred due to the chronic nature of the condition. 1, 3, 2

• Pain management alone does not constitute sufficient treatment—underlying bladder symptoms must also be addressed 1, 3
• Due to the global opioid crisis, use chronic opioids judiciously and only after informed shared decision-making with periodic follow-ups to assess efficacy, adverse events, compliance, and potential for abuse 1
• If pain management is inadequate, refer to pain specialists 3

Treatments That Should NOT Be Offered

• Long-term oral antibiotics (no benefit for non-infectious condition) 2
• Intravesical BCG (lack of efficacy) 2
• Intravesical resiniferatoxin (two high-quality RCTs showed no difference from placebo with adverse event rates of 52-89%) 1
• High-pressure, long-duration hydrodistension (increased serious adverse events including bladder rupture) 1, 2
• Systemic long-term glucocorticoids (serious adverse events including new diabetes onset, pneumonia with septic shock, increased blood pressure outweigh benefits) 1

Critical Documentation and Patient Education

• Document baseline symptoms using validated tools such as the Interstitial Cystitis Symptom Index (ICSI) or Genitourinary Pain Index (GUPI) to measure treatment effects 3, 6
• Educate patients that IC/BPS is a chronic disorder requiring continual and dynamic management with typical course involving symptom exacerbations and remissions 1, 2
• Set realistic expectations: no single treatment is effective for the majority of patients, and acceptable symptom control may require trials of multiple therapeutic options (including combination therapy) 1, 2
• Treatment efficacy for any individual is unpredictable 2, 6

Common Pitfalls to Avoid

• Never prescribe pelvic floor strengthening exercises—only relaxation techniques should be used, as strengthening worsens symptoms 1, 2
• Do not use pain management as monotherapy without addressing underlying bladder symptoms 1, 3
• Ensure ophthalmologic examinations for patients on pentosan polysulfate before starting and periodically during treatment 2, 6
• Avoid starting multiple treatments simultaneously—use stepwise escalation to identify what works 1, 2
• Do not abandon behavioral modifications when starting pharmacotherapy—maintain multimodal approach throughout 1, 2