Treatment of Interstitial Cystitis with SSRIs
SSRIs are not recommended for the treatment of interstitial cystitis and should be avoided. There is no evidence supporting their use for this condition, and they may potentially worsen symptoms given their effects on bladder function.
Why SSRIs Are Not Appropriate
SSRIs lack efficacy for bladder pain syndromes. The American Gastroenterological Association explicitly recommends against using SSRIs even for irritable bowel syndrome (a related visceral pain condition), citing that they did not significantly improve global symptoms or pain (RR 0.74; 95% CI 0.52-1.06), with the upper confidence interval boundary suggesting possible worsening of symptoms 1.
SSRIs increase gastrointestinal and bladder motility through increased serotonin concentration at nerve endings, which could theoretically exacerbate urinary frequency and urgency—core symptoms of interstitial cystitis 1.
SSRIs have no demonstrated impact on visceral sensation, which is a critical component of bladder pain in interstitial cystitis 1.
Recommended Treatment: Tricyclic Antidepressants (TCAs)
Amitriptyline is the evidence-based neuromodulator of choice for interstitial cystitis, not SSRIs.
Start amitriptyline at 25 mg at bedtime and gradually increase to 75 mg over 3 weeks as tolerated 2.
Amitriptyline demonstrated significant improvement in pain, daytime frequency, dyspareunia, and urinary urgency in patients with interstitial cystitis who had failed standard therapies, with 8 of 20 patients achieving virtual total remission 2.
TCAs work through multiple mechanisms including inhibition of serotonin and noradrenergic reuptake, blockade of muscarinic receptors (reducing bladder spasm), and effects on pain modulation—all beneficial for interstitial cystitis 1.
TCAs are superior to SSRIs for visceral pain conditions, with demonstrated efficacy for global symptom relief (RR 0.67; 95% CI 0.54-0.82) and pain relief in related conditions 1.
Multimodal Therapy Approach
Interstitial cystitis requires addressing multiple pathophysiologic components simultaneously:
Combine amitriptyline with antihistamines (hydroxyzine) to address mast cell activation, which is a key component of the disease cascade 3, 4.
Add oral pentosan polysulfate to help restore the dysfunctional urothelial glycosaminoglycan layer 5, 3.
Consider intravesical "rescue" therapy with lidocaine and heparin solutions for immediate symptom relief while oral medications take effect 3.
Critical Pitfall to Avoid
Do not prescribe SSRIs like fluoxetine (Prozac) for interstitial cystitis. This represents a fundamental misunderstanding of the condition's pathophysiology and available evidence. The lack of efficacy data for SSRIs in bladder pain syndromes, combined with their potential to worsen urinary symptoms through increased bladder motility, makes them an inappropriate choice 1, 5.