Pharmacologic Management of Painful Bladder Syndrome/Interstitial Cystitis

Abstract

Background: More than 180 different types of therapy have been used in the treatment and management of painful bladder syndrome/interstitial cystitis (PBS/IC), yet evidence from clinical trials remains inconclusive. This study aimed to evaluate the efficacy of pharmacologic approaches to PBS/IC, to quantify the effect size from randomized controlled trials, and to begin to inform a clinical consensus of treatment efficacy for PBS/IC. Methods: We identified randomized controlled trials for the pharmacologic treatment of patients wth PBS/IC diagnosed on the basis of National Institute of Diabetes and Digestive and Kidney Diseases or operational criteria. Study limitations include considerable patient heterogeneity as well as variability in the definition of symptoms and in outcome assessment. Results: We included a total of 1470 adult patients from 21 randomized controlled trials. Only trials for pentosan polysulfate sodium had sufficient numbers to allow a pooled analysis of effect. According to a randomeffects model, the pooled estimate of the effect of pentosan polysulfate therapy suggested benefit, with a relative risk of 1.78 for patient-reported improvement in symptoms (95% confidence interval, 1.34-2.35). This result was not heterogeneous (P=.47) and was without evidence of publication bias (P=.18). Current evidence also suggests the efficacy of dimethyl sulfoxide and amitryptiline therapy. Hydroxyzine, intravesical bacille Calmette-Guérin, and resiniferatoxin therapy failed to demonstrate efficacy, but evidence was inconclusive owing to methodological limitations. Conclusions: Pentosan polysulfate may be modestly beneficial for symptoms of PBS/IC. There is insufficient evidence for other pharmacologic treatments. A consensus on standardized outcome measures is urgently needed.

Urothelial Signaling

“…When damaged, the urothelium may become permeable to urine components, which may result in local inflammation, neural sensitization, and subsequent pain, frequency, and urgency (208). Important components of the GAG layer include chondroitin sulfate, hyaluronic acid, heparin sulfate, dermatan sulfate, and keratin sulfate (135), and some agents with GAG-like properties, such as sodium hyaluronate, heparin, and pentosan polysulfate, have been admin-istered intravesically to IC/BPS patients with variable results (87,208,233). In rats, hyaluronic acid was shown to reduce NGF production and bladder overactivity in a cyclophosphamide (CYP)-induced cystitis rat model (133).…”

Developmental Influences on Medically Unexplained Symptoms

“…First, it provides a more parsimonious explanation for many findings that have been quite difficult to account for, including the unfortunate lack of beneficial effect of therapies directed at the peripheral organ of interest to a particular medical subspecialty [91, 92], the presence of multiple comorbid disorders in many patients with MUS, but not in patients with other individual organ diseases, the unpredictable order of appearance of the comorbidities, and the altered functioning of the hypothalamic-pituitary-adrenal and autonomic axes of the stress response system. Second, and more importantly, it invites investigation of new areas of therapy that may otherwise escape consideration.…”

The challenge of bladder pain syndrome

“…A large systematic review of 1470 patients from 21 randomised controlled trials reported a modest benefit, with a relative risk of 1.78, for patientreported improvement in symptoms. 11 Sodium hyaluronate and chondroitin sulfate (iAluRil) -Giberti et al reported a statistically significant improvement in interstitial cystitis symptom index score (ICSI) post-treatment in 20 patients treated with this combination therapy. 12 Alkalinised lignocaine (with bicarbonate) -A randomised controlled trial of 102 patients by Nickel et al reported 30% of patients experienced significant improvement in their symptoms after completing a five-day course of treatment.…”