Interstitial Cystitis: Drug Therapy

Therapeutic targets

  • Symptomatic therapy – primarily analgesia (pain relief).
  • Restoration of the damaged GAG layer/bladder protective layer (GAG = glycosaminoglycans) of the mucosa of the bladder wall.
  • Relaxation of detrusor cells (Musculus detrusor vesicae/smooth muscle cells in the bladder wall).
  • Influencing the activity of mast cells
  • Immunomodulation (influencing the immune system).
  • Prevention of infections

Therapy recommendations

  • Analgesia (pain relief) according to WHO staging scheme (to alter peripheral nociception/perception of pain):
    • Non-opioid analgesic (acetaminophen, first-line agent).
    • Low-potency opioid analgesic (e.g., tramadol) + non-opioid analgesic.
    • High-potency opioid analgesic (eg, morphine) + non-opioid analgesic.
  • Restoration of the damaged GAG layer.
    • oral therapy
      • Sodium pentosan polysulfate* (PPS) (elmiron): 3 x 100 mg/day [only drug approved in Europe for the treatment of interstitial cystitis].
        • Improvement at 300-900 mg/day
        • Minimum duration of therapy of 3-6 months recommended (onset of effect usually after 3 to 6 months).
    • Topical (local) therapy – less side effects.
      • Instillations (bladder irrigation) – Following initital therapy should be 2-4 applications per month (maintenance therapy 1 time per month).
    • If necessary, also intravesical therapy with hyaluronic acid / hyaluronan – should also repair the GAG layer of the bladder mucosa.
    • If the potassium chloride test is positive, regeneration of the GAG layer can be considered using chondroitin.
  • Relaxation of detrusor cells – botulinum toxin injections or anticholinergics (they reduce detrusor pressure and thus urge symptoms).
  • Antidepressants – this is not about the antidepressant effect, but relief of pain and urge symptoms, which can be achieved by antidepressants; in addition, antidepressants have anxiolytic (anxiety-relieving), sedative (calming) effects and lead to mast cell suppression; about 50% respond to treatment
    • Amitriptyline: 10-90 mg/day (max 150 mg/day).
    • Nortriptyline: 10-90 mg/day (max 150 mg/day).
    • Opipramol: 50 mg/day (max. 300 mg/day).
    • Note: on-and-off dosing (start with 10 mg/day).
  • Alpha-2 receptor antagonists (eg, mirtazapine) are an alternative to the above antidepressants without anticholinergic side effects.
  • Alpha-blockers (e.g., tamsulosin) cause relaxation of urethral, bladder neck, and prostate smooth muscle.
  • Muscle relaxants (e.g., tizianidine): tizianidine is a centrally acting myotonolytic (muscle relaxant) that leads to centrally mediated modification of pain
  • If necessary, also microbiological therapy: this can regulate dysfunction of the mucous membranes and the immune system.
  • If necessary, also micronutrient therapy to compensate for micronutrient deficiencies.
  • Immunosuppression
    • Cyclosporine A (“off-label-use”).
      • Anti-inflammatory (anti-inflammatory).
      • Response rate for Hunner-type interstitial cystitis up to 68% and for non-Hunner type 30%.
      • Close monitoring because of side effects
      • Combination with sodium pentosan polysulfate (PPS) superior to PPS alone.
  • Preventing infections – In patients with interstitial cystitis, the GAG layer is damaged, making it easier for bacteria to attach and cause bladder infections. For infection prophylaxis, we recommend:
    • Angocin – nasturtium and horseradish root.
    • D-mannose powder
    • Goldenrod extract
    • Cranberry juice
    • Vitamin C – high dose
  • There is limited evidence for the following medicines:
    • Prostaglandin E1 – cytoprotective (cell-protective), H1 receptor blockade, “off-label-use”; high rate of side effects, pregnancy-influencing.
    • L-Argininenitric oxide synthetase inhibitor; reduction of mast cell degeneration and muscle relaxation.
    • Steroids – immunosuppressants; not suitable for long-term therapy.
    • Antihistamines – anxiolytic (anti-anxiety), sedative (calming); histamine receptor blockers.

* To date, it has not been conclusively determined whether the risk of pigmentary maculopathy ((disease of the macula; damage to the macula/site of sharpest vision on the center of the retina; potentially irreversible side effect) should be considered.