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Interstitial cystitis/bladder pain syndrome: Management

Interstitial cystitis/bladder pain syndrome: Management
Literature review current through: Jan 2024.
This topic last updated: Dec 12, 2023.

INTRODUCTION — Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition involving chronic bladder pain or discomfort that can have a profound detrimental impact on quality of life [1,2].

Challenges in developing a treatment plan stem from a lack of clear understanding of the etiology of the disorder, symptom variation across patients, and a paucity of high-quality data regarding the efficacy and safety of IC/BPS treatments (eg, few randomized trials, variation in the definition of the condition and outcome measures) [3].

The management of IC/BPS is reviewed here. The pathogenesis, clinical features, and diagnosis of this condition are discussed separately. (See "Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis".)

In this topic, when discussing study results, we will use the terms "woman/en" or "patient(s)" as they are used in the studies presented. We encourage the reader to consider the specific counseling and treatment needs of transgender and gender-expansive individuals.

OVERVIEW OF CLINICAL APPROACH — Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain syndrome of uncertain etiology. There is no curative treatment, and the goal of management is to provide symptom relief in order to achieve an adequate quality of life. There are many therapeutic approaches for IC/BPS, none of which have been proven to be helpful for all patients [4,5].

Our approach to treatment is based on individual patient characteristics, including symptom severity and progression, prior effective or ineffective treatments, and patient preference, in alignment with the American Urological Association clinical practice guidelines for the treatment of IC/BPS [6-8]. There is a paucity of high-quality data to support one treatment over another. Therefore, treatment plans are developed using shared decision-making to take patient preferences into account.

INDICATIONS FOR INITIAL REFERRAL TO A UROLOGIST — This topic applies to patients determined to have a diagnosis of IC/BPS, which is discussed elsewhere. (See "Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis".)

Although the initial management of most patients may be performed by a primary care clinician, certain patients with IC/BPS such as those with concurrent bladder dysfunction (urinary incontinence, incomplete bladder emptying), or structural bladder issues (eg, due to prior pelvic surgery) should be evaluated by a urologist prior to treatment.

INTERVENTIONS FOR ALL PATIENTS

Patient education — We provide education as the first step in the management of patients with IC/BPS including information about the diagnostic criteria, variability of symptoms, and chronic nature of the condition [6]. We review normal bladder function and encourage patients to identify activities, foods, or behaviors that may exacerbate symptoms. (See 'Self-care and lifestyle modification' below.)

Many patients have gone through a long diagnostic process during which they have encountered clinicians who were unfamiliar with IC/BPS and may have regarded the symptoms with uncertainty and skepticism. Arriving at a diagnosis of IC/BPS often provides considerable relief and validation for these patients.

We counsel patients about reasonable expectations regarding treatment course and outcomes. Patients are advised that adequate symptom relief is achievable but that this may require multiple trials of different types of therapies.

Evaluate for comorbid conditions — We evaluate all patients for acute and chronic conditions which may exacerbate IC/BPS symptoms, and we treat as appropriate.

Acute conditions include genitourinary disorders such as urinary tract infection or vulvovaginitis. We do not use antibiotics empirically. Specifically, we do not treat with antibiotics in the absence of a diagnosis of urinary tract infection.

Chronic disorders include vulvodynia, endometriosis or other etiologies of chronic pelvic pain or dysmenorrhea, inflammatory bowel disease, diverticulitis, irritable bowel syndrome, and fibromyalgia, all of which can result in increased bladder sensitivity [9]. Collaboration with other clinicians who have expertise in these conditions is usually necessary. (See "Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis", section on 'Associated conditions'.)

Evaluate psychosocial needs — Psychosocial support is an integral part of treatment of any chronic pain disorder, including IC/BPS. We assess all patients for depression, anxiety, and stress and offer appropriate treatment strategies.

Some IC/BPS patients benefit from training in stress reduction and relaxation techniques [4,10,11]. Greater levels of stress have been shown to increase IC/BPS symptoms [12,13], and maladaptive coping strategies have been demonstrated to have an adverse effect on symptoms [14]. (See "Complementary and alternative treatments for anxiety symptoms and disorders: Physical, cognitive, and spiritual interventions".)

Disorders such as depression and anxiety are common in patients with chronic pain and may impede treatment success [15,16]. Referral to a psychotherapist with expertise in working with patients with chronic pain should be considered if there is suspicion that depression or anxiety is present. Approaches such as cognitive behavioral therapy [17] that have been found to be helpful in other chronic pain conditions may be appropriate. (See "Approach to the management of chronic non-cancer pain in adults", section on 'Nonpharmacologic therapies'.)

We encourage interested patients to be in touch with local pain support groups or with national support groups, such as the Interstitial Cystitis Association or the Interstitial Cystitis Network.

Self-care and lifestyle modification — Self-care practices and lifestyle modification are discussed with all patients and implemented if feasible. In some patients, these measures may be effective alone, although in our experience, the majority of patients will require additional therapy. Such strategies include [6]:

Application of local heat or cold over the bladder or perineum.

Avoidance of activities or food or beverages that exacerbate symptoms (eg, caffeine, alcohol, artificial sweeteners, hot pepper, and vitamin C-containing foods) [18]. Providing a list that indicates foods to limit or avoid is helpful for patients [19]. These foods may be avoided until symptoms resolve, at which time they may be reintroduced. The Interstitial Cystitis Association provides online diet advice for patients [20]. Research about the impact of food on IC/BPS is very limited; however, in a trial of 30 patients, those who followed a specially developed diet experienced improvement in symptoms at three months and one year compared with those who followed a usual diet [21].

Avoidance of exercises, recreational activities, sexual activities, or body positions that seem to worsen the bladder symptoms. A symptom diary may be useful for some patients to self-identify such factors.

Fluid management – A fluid and voiding diary (form 1) can provide information to guide recommendations for fluid management; such recommendations should be individualized for each patient. Patients who experience worsening of symptoms with concentrated urine may find increasing fluid intake helpful. Others who experience pain with bladder filling may find that moderate fluid restriction provides some relief. However, patients should be instructed to avoid extremes of fluid intake. In most patients, it is not necessary to drink more than 2 L of fluid per day. Those who restrict fluids should strive to maintain a pale yellow color to their urine.

Bladder training with urge suppression. (See "Female urinary incontinence: Treatment", section on 'Bladder training'.)

The effectiveness of a behavior modification program was supported by data from the control group of a trial comparing amitriptyline with a program of education, symptom management (muscle stretching, application of heat/cold, avoidance of pain triggers), fluid management, diet modification, and bladder training among 271 patients with IC/BPS [22]. At 12 weeks, 55 percent of the treatment group and 45 percent of the control group reported moderate or marked improvement in symptoms.

PHYSICAL THERAPY FOR PATIENTS WITH PELVIC FLOOR MUSCLE TENDERNESS — Many patients with interstitial cystitis/bladder pain syndrome (IC/BPS) have pelvic floor muscle tenderness on examination [23]. We use physical therapy for these patients, especially if palpation of the muscles reproduces their pain symptoms [24,25]. We suggest a 12-week course of physical therapy alone, or in combination with other treatments.

Pelvic physical therapy includes treatment of the pelvic muscle tender points, trigger points, connective tissue restrictions, and muscular abnormalities of the soft tissues. Pelvic floor strengthening exercises (eg, Kegel exercises) should be avoided, as they may exacerbate the pelvic pain symptoms [7]. This type of treatment is provided by a physical therapist with specialized training in pelvic soft tissue manual manipulation and rehabilitation. Physical therapists in the United States who focus on pelvic physical therapy for women can be found through the American Physical Therapy Association. (See "Myofascial pelvic pain syndrome in females: Pelvic floor physical therapy for management".)

In a trial among 81 women with IC/BPS who demonstrated pelvic floor muscle tenderness, a higher proportion of those randomized to pelvic floor myofascial physical therapy reported moderate or marked symptom improvement compared with those who received traditional full-body therapeutic massage (59 versus 29 percent, respectively) [26].

PHARMACOLOGIC THERAPY

Principles — Although some patients have adequate symptom resolution with nonpharmacologic interventions as described above, many will also require pharmacologic therapy. For patients who have occasional symptom flares, such pharmacologic therapy can be limited to analgesics. (See 'Adjuvant/rescue analgesia' below.)

However, for patients in whom flares are frequent, or in whom symptoms are more severe, we initiate oral medications as initial pharmacotherapy. The decision of when to initiate oral therapy must be individualized, taking into account the severity of symptoms, the frequency of flares, patient preference, and the potential adverse effects of continued reliance on analgesic use. In certain patients, it may be appropriate to combine medications, especially if some symptom improvement is noted after an initial medication trial. However, clinicians should be aware of polypharmacy risks and should consider discontinuing medications that have not provided clear improvement.

Amitriptyline as first-line therapy — We use amitriptyline as initial pharmacologic therapy of interstitial cystitis/bladder pain syndrome (IC/BPS). However, there are few comparative studies of oral medications for IC/BPS and the choice of agent depends upon the risk of adverse effects and patient preference. Tricyclic antidepressants such as amitriptyline are an attractive option as they are believed to have analgesic properties and may also relieve the depressive symptoms associated with chronic pain. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Tricyclic antidepressants'.)

Dosing and adverse effectsAmitriptyline appears to be most effective at higher doses, although these doses can be limited by adverse effects. The typical dosing regimen starts with 10 mg at bedtime, escalating at weekly intervals to 25, 50, and 75 mg (or to the maximum tolerated dose). Adverse effects include anticholinergic effects (eg, dry mouth, urinary retention, constipation), sedation, weight gain, orthostatic hypotension, and cardiac conduction abnormalities. If effective, results can be observed within one month after initiation of therapy. (See "Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects", section on 'Amitriptyline'.)

ContraindicationsAmitriptyline should not be given concomitantly with monoamine oxidase inhibitors, since this may cause serotonin syndrome. It should not be given with cisapride due to increased risks of cardiac arrhythmia, nor should it be used during the acute recovery phase following myocardial infarction. Coadministration with drugs that inhibit cytochrome P450 (eg, selective serotonin inhibitors, cimetidine, many anticonvulsants) should be avoided as they may increase serum levels and result in toxicity. (See "Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects", section on 'Side effects'.)

Supporting data and dose-effect – The efficacy of amitriptyline is best demonstrated at higher doses (ie, 50 mg daily). In one trial (n = 50) a higher proportion of patients treated with amitriptyline (25 to 100 mg daily) had a >30 percent decrease in a symptom score compared with those given placebo treatment (42 versus 13 percent) [27]. In another trial (n = 271) which reported results based on dose, a higher proportion of patients treated with 10 to 75 mg of amitriptyline therapy had improvement in symptoms compared with those on placebo (55 versus 45 percent), although a greater degree of improvement compared with placebo was seen in the subgroup of patients (n = 106) who were able to tolerate doses of at least 50 mg daily (77 versus 53 percent) [22].

Pentosan polysulfate sodium as alternative — Pentosan polysulfate sodium (PPS; commercial name Elmiron) is the only oral medication approved by the US Food and Drug Administration (FDA) for treatment of IC/BPS; however, concerns regarding risk of progressive macular eye disease limit its widespread use. It is believed to reconstitute the protective glycosaminoglycan layer over the urothelium thought to be deficient in IC/BPS.

Efficacy and dose – In a meta-analysis of six trials, treatment with PPS resulted in a 12 percent improvement, in both overall symptoms and pain, and a 9 percent improvement in urgency compared with placebo [28]. The typical regimen is 100 mg three times daily. PPS may not result in relief of symptoms for three to six months after initiation of treatment, so patients must be willing to accept a drug trial of at least that duration. It can also be used intravesically, although we do not do so in our practice. (See "Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis", section on 'Pathogenesis'.)

Risk of macular eye disease – There have been reports of macular eye disease in patients who have taken PPS [29-33]. The etiology is unclear, and cumulative dose appears to be a risk factor; however, the incidence is unknown. Most cases have occurred after at least three years of use, although some have occurred after shorter durations. Visual symptoms have included difficulty reading, slow adjustment to low or reduced light environments, and blurred vision. In one study of 26 eyes with PPS maculopathy and >3000 g cumulative PPS exposure, macular changes continued to progress 13 to 30 months after drug cessation [33].

Other adverse effects – Other side effects occur in approximately 10 to 20 percent of patients, are typically mild, and can include nausea and diarrhea [6]. PPS may also be associated with hair loss; although, this side effect is mild and reversible. Rarely, it has been associated with mild elevation in liver function enzymes, and therefore, it should be used with caution in patients with known hepatic dysfunction.

Warnings and guidance

United States – Given these findings, the FDA approved a new warning label for PPS in June 2020 which states the following [34]:

-A detailed ophthalmologic history should be obtained in all patients prior to starting treatment with PPS.

-For patients with pre-existing ophthalmologic conditions, a comprehensive baseline retinal examination is recommended prior to starting therapy.

-In addition, a retinal examination is suggested for all patients within six months of initiating treatment and periodically while continuing treatment. If pigmentary changes in the retina develop, then risks and benefits of continuing treatment should be re-evaluated, since these changes may be irreversible.

Canada – In Canada, the use of PPS is contraindicated in persons with a history of macular pathology [35].

Antihistamines for patients with allergic disorders — For the subset of patients with both IC/BPS and allergic disorders (eg, seasonal allergies, asthma), we use an antihistamine as the initial oral medication. This approach is based upon the hypothesis that hypersensitivity may be responsible for bladder symptoms based on the finding of increased mast cells in the bladder wall. Also based upon this potential mechanism, there are a few reports of use of montelukast as treatment for IC/BPS, although further data are needed and we do not use it in our practice [36,37]. (See "Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis", section on 'Pathogenesis'.)

Hydroxyzine is the most commonly used antihistamine for the treatment of IC/BPS. The typical dose is 25 to 50 mg at bedtime. It is usually well tolerated but may cause sedation or dizziness. Patients usually see a response within a few days. The sedative qualities may be helpful in patients who complain of insomnia due to nocturia.

There are no high-quality data to support treatment of IC/BPS with hydroxyzine. In one trial (61 patients) a trend towards greater response was seen in patients treated with hydroxyzine compared with placebo (31 versus 20 percent); however, larger trials are needed to confirm this effect [38].

Adjuvant/rescue analgesia — We use analgesics primarily as adjuvant therapy (see 'Principles' above). As such, analgesics may be used at any point in treatment with the goal of minimizing pain and maximizing function [6,7]. In some patients with IC/BPS, as with other chronic pain conditions, long-term use of oral analgesics may be necessary. Such patients may benefit from referral to a specialist in pain management. (See "Approach to the management of chronic non-cancer pain in adults".)

In our practice, we typically use nonsteroidal anti-inflammatory drugs (NSAIDs; eg, ibuprofen at standard over-the-counter dosing) and other over-the-counter medications, such as acetaminophen, as oral pain medications. Tramadol and other narcotics are other options, although we do not use these often in our practice due to concerns of dependency.

In addition, we use oral urinary analgesics for short-term relief of urinary symptoms, either alone or in combination with NSAIDS.

Phenazopyridine is intended only for use for up to two days, in conjunction with antibiotics, when treating urinary tract infection [39]. Data to inform duration of treatment specific to patients with IC/BPS are lacking. According to the manufacturers, it is contraindicated in patients with a glomerular filtration rate (GFR) <50 mL/min; however, some UpToDate contributors would consider usage for one to three days for patients with estimated GFR >45 mL/min. Long-term use of this drug is avoided as it has been associated with methemoglobinemia and other complications such as renal or liver dysfunction [40-43].

Methenamine may be used short term in the absence of contraindications such as renal impairment and severe hepatic impairment, and it should be avoided in patients with gout, according to the manufacturers.

In patients who are experiencing an acute episode of severe bladder pain, we use intravesical instillation of lidocaine with heparin and/or sodium bicarbonate. This treatment requires bladder catheterization and should be reserved for patients who have not found relief with urinary analgesics or oral pain medications or with other IC/BPS treatments. Lidocaine can be combined with other intravesical therapies. (See 'Intravesical therapies' below.)

Other oral medications

Neuropathic pain agents – We have found that certain patients may experience symptom improvement with pregabalin (Lyrica) or gabapentin (Neurontin). However, there are no published studies for the use of these meds for IC/BPS.

Cimetidine – Although cimetidine has been used as a treatment for IC/BPS, there are limited data to support its use, and we have not found it to be effective in our clinical experience [44].

Sildenafil – Similarly, the data to support the use of sildenafil are limited, and we do not use it in our clinical practice as we have not found it to be effective [45].

ASSESSING RESPONSE TO INITIAL THERAPY — We assess patient response to therapy at follow-up visits, the timing of which is determined by the symptom severity and time to effect of the treatment chosen. However, in general, we see patients for a follow-up visit two or three months after initiation of treatment. If the symptoms have persisted, we will consider office cystoscopy to assess for the presence of Hunner lesions. (See 'Treatment of Hunner lesions' below.)

We utilize the Genitourinary Pain Index (GUPI) at both the initial and follow-up visits to help determine treatment response [46]. The GUPI is a self-administered index that has versions for men and women. While there is no standard threshold for determining treatment success or failure, a reduction of seven points is highly correlated with treatment response [46].

Patients often require several treatment trials of different modalities before achieving substantial symptom improvement. However, the diagnosis of IC/BPS should be reconsidered if no improvement occurs after several trials of differing therapies. In such cases, referral to a urologist is appropriate.

PATIENTS WITH REFRACTORY SYMPTOMS — We typically use bladder hydrodistention or intravesical therapies only if initial trials of oral agents are not successful in reducing symptoms, or if the patient demonstrates a rapid progression of symptoms.

Although patient preference is an important determinant in the choice between hydrodistention and intravesical instillation therapies, we typically perform bladder hydrodistention therapy before intravesical therapies as it can provide additional diagnostic information (eg, presence of Hunner lesions, bladder capacity) and, if effective, typically requires fewer treatments.

Bladder hydrodistention — Bladder hydrodistention is a procedure in which a cystoscope is used to fill the bladder with water in order to stretch the bladder wall. It has traditionally been used for diagnostic purposes but has also been considered therapeutic because some patients have prolonged relief of symptoms after the procedure. The beneficial effect is possibly due to the disruption of sensory nerves within the bladder wall [47]. It may be performed in any patient with interstitial cystitis/bladder pain syndrome (IC/BPS), and treatment of Hunner lesions (if present) can typically be performed during the same procedure. (See "Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis", section on 'Identification of characteristic bladder lesions'.)

The technique has not been standardized, but hydrodistention is usually performed under general anesthesia or with deep sedation, using a distention pressure of 60 to 80 cm H2O for a duration of less than 10 minutes. The use of higher pressures or longer distention times has been associated with bladder wall necrosis and/or bladder rupture [48,49].

The disadvantages of hydrodistention are that some patients experience a temporary worsening of their symptoms following the procedure and any beneficial effect is usually short lived (<6 months) [50-52]. Repetitive therapeutic hydrodistention is reserved for patients who obtain significant and prolonged (>6 months) relief.

In a systematic review of studies evaluating hydrodistention for treatment of IC/BPS, the best symptomatic response was a subjective improvement in 57 percent of patients [53].

Treatment of Hunner lesions — A subset of IC/BPS patients demonstrate Hunner lesions on cystoscopy. (See "Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis", section on 'Identification of characteristic bladder lesions'.)

We treat Hunner lesions in patients in whom they are found. Options include resection, electrical cauterization, or injection with a corticosteroid. All of these approaches have been found to be helpful, although periodic retreatment is usually required [54-56]. The duration of treatment effect is variable but can sometimes last 12 months or longer.

Intravesical therapies — Intravesical therapy is used to instill medications directly into the bladder using a urinary catheter. We typically use this treatment for symptom flares.

Regimen – The usual regimen is one instillation per week for six weeks, although the treatments can be done more frequently. Some patients choose to do the weekly instillations at home as chronic maintenance therapy.

Instillation medications – Evidence-based consensus on the optimal drug combination for intravesical instillation is lacking. A variety of medications are used, often in combination [8,57,58]:

Local anesthetics (eg, lidocaine, bupivacaine)

Glycosaminoglycans (GAGs; eg, heparin, hyaluronic acid)

Sodium bicarbonate

Steroids (eg, solumedrol)

Dimethylsulfoxide (DMSO)

Antibiotics (eg, gentamicin)

We typically use a combination of:

2% lidocaine (or 0.5% bupivacaine) – 20 mL

Heparin 10,000 units/10 mL – 10 mL

Solumedrol 125 mg/2 mL – 2 mL

Sodium bicarbonate 8.4% or 7.5% – 20 mL

Gentamicin (80 mg/2 mL; to reduce risk of post-instillation urinary tract infection) – 2 mL

Potential adverse effects of bladder instillations include urinary tract infection, dysuria, urethral irritation, and increased bladder pain.

Drug-specific data include:

Glycosaminoglycans (GAGs) – Intravesical instillation of GAGs has produced some symptom relief in patients with IC/BPS [59]. The rationale for instillation therapy is that it delivers high concentrations of the GAG agent to the target tissue (bladder lining) with a low risk of systemic adverse effects [60]. In a meta-analysis of five trials and 14 studies of various intravesical treatments among patients with IC/BPS, high molecular weight hyaluronan (commercial name Cystistat) had the largest effect size for symptom reduction and response rate [61]. However, study limitations include a small number of trials, lack of placebo-controlled trials directly comparing agents, use of different treatment frequencies and durations, and heterogeneous inclusion criteria.

Dimethylsulfoxide (DMSO) – The mechanism of action of DMSO is thought to be multifactorial, including anti-inflammatory, analgesic, smooth muscle relaxation, and mast cell inhibition effects [62]. The efficacy of DMSO was supported by two small randomized trials [63,64].

OTHER THERAPIES — These therapies are reserved for patients with symptoms that significantly affect quality of life, who have failed other measures, and who are aware of and willing to accept the risk of adverse effects. They should be administered only by clinicians who have experience with use of these approaches in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) and with management of the adverse effects that may occur. At this time, there are insufficient data to determine which of these treatments is preferable. Typically, this decision is made based on patient preferences after discussion of the potential adverse effects.

Intradetrusor botulinum toxin — The use of intradetrusor injection of botulinum toxin (BoNT) for treatment of IC/BPS may be combined with hydrodistention [65-74]. While BoNT may alleviate symptoms of IC/BPS, there is a risk of urinary retention, which may be particularly problematic for a patient with a painful bladder. Any patient considering this treatment must be willing and able to perform intermittent self-catheterization. Use of BoNT for this indication is not approved by the US Food and Drug Administration (FDA), and payment may not be covered by health insurance. (See "Botulinum toxin for treatment of lower urinary tract conditions: Indications and clinical evaluation", section on 'Pelvic pain syndromes'.)

The mechanism of the effect of BoNT therapy for IC/BPS is likely the ability of BoNT to modulate sensory neurotransmission. BoNT-A is the serotype most commonly used; it is available as onabotulinumtoxinA (Botox) and abobotulinumtoxinA (Dysport). (See "Botulinum toxin for treatment of lower urinary tract conditions: Indications and clinical evaluation", section on 'Background for botulinum toxin use'.)

In a trial of 67 patients randomized to receive suburothelial injection of BoNT-A (100 or 200 units) combined with hydrodistention, or hydrodistention alone, BoNT-A treatment resulted in a higher proportion of patients with moderate or marked improvement in symptoms at three-month follow-up (71 versus 48 percent), and this difference was maintained through 24 months [65]. Initially, 200 units of BoNT was used, but adverse reactions occurred in 9 of 15 patients (four patients had acute or chronic urinary retention, seven had severe dysuria) and the dose was decreased to 100 units. With the 100-unit dose, the number of adverse effects decreased but was still more frequent than for hydrodistention alone.

The 100-unit dose was further evaluated in another trial, in which 60 patients were randomized to receive suburothelial injections of BoNT-A 100 units (n = 40) or normal saline (n = 20). At week 8, a greater reduction of bladder pain was observed in the BoNT-A treatment group, with treatment success rates of 63 percent in the BoNT-A groups and 15 percent in the normal saline group [66].

Sacral neuromodulation — Neuromodulation is a surgical procedure that has not been well studied for the treatment of IC/BPS. An implantable device for sacral neuromodulation (SNM; eg, InterStim) is approved by the FDA for treatment of urinary urgency and frequency but not for treatment of IC/BPS.

The SNM device consists of an implanted lead that lies along a sacral nerve root (usually S3 nerve root) and is attached to an implanted pulse generator. Alternatively, the lead can be placed to stimulate the pudendal nerve. A small trial found a greater degree of improvement in symptoms with pudendal rather than sacral placement (59 versus 44 percent) [75].

Observational studies suggest symptomatic relief (eg, improvement in nighttime voiding frequencies and pain); however, the rate of reintervention is high due to device malfunction, treatment failure, or loss of benefit [75-80].

Cyclosporine A — The use of oral cyclosporine A (CyA) has been reported to decrease symptoms in some patients with IC/BPS, especially those with Hunner lesions, although the efficacy is supported by scant or low-quality data [81-83]. Use of this agent is limited by potential adverse effects, including nephrotoxicity, hypertension, immunosuppression, hair growth, gingival hyperplasia, paresthesias, abdominal pain, flushing, and muscle pain. CyA should be administered only by clinicians who have experience with its use in patients with IC/BPS and with management of the adverse effects that may occur.

The only trial (n = 64) to evaluate this therapy compared six months of treatment with oral CyA (1.5 mg/kg twice daily) to pentosan polysulfate sodium (PPS; 100 mg PPS three times daily) [84]. A greater percentage of patients receiving CyA showed improvement on a symptom scale (75 versus 19 percent) and greater reduction in urinary frequency (-6.7 versus -2.0 times per 24 hours). However, the CyA group had higher rates of overall adverse effects (94 versus 56 percent) than the PPS group. A subsequent retrospective cohort study of 51 IC/BPS patients with Hunner lesions found a CyA response rate of 84 percent, which was maintained during a three-year follow-up period [85]. In our practice, patients identified to have Hunner lesions are managed initially with local treatment (cystoscopic cautery/steroid injection). Those who demonstrate a rapid recurrence of the Hunner lesions are started on oral CyA therapy, which helps to maintain symptom control in the majority of patients [86].

URINARY DIVERSION AS LAST RESORT — Urinary diversion is the treatment of last resort for interstitial cystitis/bladder pain syndrome (IC/BPS). It is a surgical procedure that may result in substantial perioperative and ongoing morbidity. This procedure is reserved for patients who meet the following criteria:

Symptoms significantly affect quality of life

Other etiologies of symptoms have been excluded

All other IC/BPS therapies have failed

Patient values relief of symptoms more than the risks and lifestyle changes associated with the procedure

Urinary diversion involves dividing the ureters at their junction with the bladder and diverting the urine into an incontinent urostomy or a continent catheterizable urine pouch. These complex reconstructive surgeries utilize bowel segments to form the new urine reservoirs. Urinary diversion will reliably relieve symptoms of frequency and nocturia, but pelvic pain may persist even if concomitant cystectomy is performed [87,88].

Urinary diversion procedures are discussed in detail separately. (See "Urinary diversion and reconstruction following cystectomy".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are the best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword (s) of interest.)

Basic topics (see "Patient education: Bladder pain syndrome (interstitial cystitis) (The Basics)")

Beyond the Basics topics (see "Patient education: Diagnosis of interstitial cystitis/bladder pain syndrome (Beyond the Basics)" and "Patient education: Treatment of interstitial cystitis/bladder pain syndrome (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Definition and overview – Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain syndrome of uncertain etiology. There is no uniformly curative treatment, and the primary goal of management is to provide symptom relief in order to achieve an adequate quality of life. Our approach to treatment is based on individual patient characteristics, including symptom severity and progression, prior effective or ineffective treatments, and patient preference. (See 'Overview of clinical approach' above.)

Management in primary care setting – The initial management of most IC/BPS patients may be performed by a primary care clinician; however, patients who have concurrent bladder dysfunction (urinary incontinence, incomplete bladder emptying) or structural bladder issues (eg, due to prior pelvic surgery) should be evaluated by a urologist prior to treatment. (See 'Indications for initial referral to a urologist' above.)

Patients often require several treatment trials of different modalities before achieving substantial symptom improvement.

The diagnosis of IC/BPS should be reconsidered if no improvement occurs after several trials of differing therapies. In such cases, referral to a urologist is appropriate. Cystoscopy can then be performed to assess for Hunner lesions. (See 'Assessing response to initial therapy' above.)

Initial treatment modalities – Initial measures for all patients with IC/BPS include patient education about the condition, treatment of comorbid conditions (eg, urinary tract infection, other chronic pain conditions), psychosocial support, self-care, and lifestyle modifications. (See 'Interventions for all patients' above.)

Use of analgesics – Analgesics may be used in IC/BPS patients at any point in treatment with the goal of minimizing pain and maximizing function. Pain medications are used for short-term relief for flares of bladder pain rather than as primary therapy. (See 'Principles' above and 'Adjuvant/rescue analgesia' above.)

-Mild to moderate pain – For patients with mild to moderate pain, we suggest nonsteroidal anti-inflammatory drugs (NSAIDs; eg, ibuprofen) or acetaminophen as an oral pain medication (Grade 2C). Tramadol and other narcotics are alternatives but may cause dependency. Urinary analgesics (eg, Phenazopyridine, Methenamine) can also be used, but only for 1 to 2 days; certain comorbidities are contraindications for these drugs.

-Severe pain – For patients with severe pain, we suggest intravesical instillation of lidocaine with heparin and/or sodium bicarbonate (Grade 2C).

Pelvic floor muscle therapy – For patients who exhibit pelvic floor muscle tenderness on examination, especially if palpation of the muscles reproduces their pain symptoms, we suggest pelvic floor physical therapy (Grade 2C). Physical therapy can be used alone or in combination with other treatments and has shown efficacy in a least one trial. (See 'Physical therapy for patients with pelvic floor muscle tenderness' above.)

Medical management of pain – For most patients with IC/BPS, we suggest amitriptyline as the initial oral medication (Grade 2C). Pentosan polysulfate sodium (PPS) is an alternative when amitriptyline is not effective or causes bothersome adverse effects. However, PPS should be used with caution due to its association with irreversible retinal abnormalities (eg, macular eye disease). Patients who are prescribed PPS require periodic ophthalmology examinations. (See 'Pharmacologic therapy' above.)

For the subset of patients with both IC/BPS and allergic disorders, we use an antihistamine as the initial oral medication. None of these agents have been compared with each other. Amitriptyline has somewhat more robust evidence of efficacy compared with placebo than PPS; antihistamines have not been well studied in IC/BPS. (See 'Pharmacologic therapy' above.)

We assess patient response to therapy at follow-up visits, usually two or three months after initiation of treatment. We utilize the Genitourinary Pain Index (GUPI) at both the initial and follow-up visits to help determine treatment response. (See 'Assessing response to initial therapy' above.)

Role of cystoscopy – Cystoscopy should be performed if initial treatments are not effective. This procedure evaluates for bladder pathology and also can identify Hunner lesions. These lesions can be treated with local methods (cautery, steroid injection) or with systemic cyclosporine A (CyA). (See 'Other therapies' above.)

Treatment of patient with refractory symptoms

Therapies for patients whose symptoms are refractory to initial therapy include bladder hydrodistention (with treatment of bladder wall Hunner lesions if present) or intravesical therapies. (See 'Patients with refractory symptoms' above.)

For patients with symptoms that significantly affect quality of life and who have failed other measures, possible therapies include intradetrusor botulinum toxin A or sacral neuromodulation. (See 'Other therapies' above.)

Urinary diversion is the treatment of last resort for IC/BPS. It is a surgical procedure that may result in severe perioperative and ongoing morbidity. (See 'Urinary diversion as last resort' above.)

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