The primary goal in the management of interstitial cystitis (IC) is symptom relief.
Specific drugs are available, but treatment usually is nonspecific and empiric.
Patients require support, understanding and reassurance from clinicians and family
members. Usually, patients are surprised to learn about the diagnosis; therefore,
it is important clarify that IC is neither a malignancy nor a forerunner of some
systemic disorder. 1
The key to successful treatment of IC/painful bladder syndrome (PBS) is conservative
or behavioural therapy. The principles of nonpharmacologic management are patient
education, behaviour modification for urinary urgency and frequency, physical therapy
for trigger point release, stress reduction, and dietary manipulation. The fight
against IC can be intensified by dietary modifications as a first-line therapy.
Around 50% of the IC patients are able to recognise acidic fluids or foods that
exacerbate symptoms or cause flare-ups. Common acidic foods include alcohol containing
beverages, carbonated drinks, caffeine, spicy foods, tomatoes and vinegar. Management
of mental and emotional stress is important to control the disease, although it
remains unclear whether stress is a precipitant or consequence of IC/PBS. 2, 3
Multimodal Oral Pharmacologic Approach
The pharmacologic therapy for IC/PBS aims to restore bladder surface integrity,
modulate neuronal dysfunction and reduce any coexisting inflammation. A multimodal
pharmacologic approach is required to achieve these goals by targeting specific
points in the postulated cycle of the disease process [Figure 1]. 2
Pentosan Polysulphate sodium: The only approved drug
The only oral drug currently approved by the US Food and Drug Administration (FDA)
for the treatment of IC is pentosan polysulphate sodium (PPS). It provides the bladder
with a compound structurally similar to bladder surface glycosaminoglycan (GAG)
layer. Though its mechanism of action largely remains unclear, it promotes restoration
of the defective layer, thereby, preventing further urothelial insult. The approved
dose of PPS is 100 mg three times per day. Although its action seems to be beneficial
to most of the patients, some of them respond slowly to treatment, with symptom
relief noted after several months. Treatment with PPS should continue for at least
6 months.2,4 Common adverse effects associated with PPS therapy include diarrhoea,
dyspepsia, reversible alopecia, headache, rash, dizziness, abdominal pain and uncommon
liver function abnormalities (1% to 4%).1
Suppression of mast cell degranulation with antihistamines
There appears to be a role of oral antihistamine hydroxyzine in the management of
IC. It is recommended to suppress mast cell degranulation, a constant feature of
the pathologic inflammatory response. Hydroxyzine is a unique antihistamine as it
brings about this specific suppression. Studies have suggested that hydroxyzine
is efficacious in patients with biopsy-proven bladder mastocytosis or mast cell
activation and history of allergies.4 Its dosing starts at 25 mg at bedtime, and
may increase to 50 to 100 mg/d during the allergy season.2,5
The beneficial effects of tricyclic antidepressants in IC include central and peripheral
anticholinergic actions, blocking reuptake of serotonin and norepinephrine, and
antihistaminic properties.3 Amitriptyline is an oral tricyclic antidepressant that
has been used in patients with IC/PBS for regulation of bladder pain and urgency
by modulating neuronal dysfunction. In addition, it also has antihistaminic properties.
As per clinical studies, amitriptyline at a dose of 25 to 75 mg/d taken at bed time
provides mild to moderate central pain modulation in majority of patients with IC/PBS.
It has been found to be safe and effective in patients with IC/PBS for up to 4 months.
Many other drugs, apart from those mentioned above, are used to alleviate the symptoms
of IC. These include sedatives to calm the patient and drugs inhibiting nociception.
Some of the commonly used drugs are doxepin and imipramine. These drugs are administered
at doses between 25mg to 75 mg at bedtime. Initial doses of these drugs could be
low, and these can be gradually titrated up until symptom relief is obtained or
until side effects become bothersome. H2-receptor antagonist cimetidine is also
effective at a dosage of 300 mg BD. Although no definite studies on efficacy of
aspirin or a nonsteroidal anti-inflammatory drug exist, some patients feel better
after taking them. This could be due to release of prostaglandins and leukotrienes
by mast cell degranulation. Bladder analgesics such as phenazopyridine or oxybutynin
chloride, and calcium channel blockers such as nifedipine or gabapentin are some
of the other drugs that are found to be beneficial for symptomatic use in patients
with IC. 1
Modalities for Treatment of Interstitial Cystitis 1
Oral drugs used in the treatment of IC/PBS are generally effective, although a few
have shown mixed results. The lack of consistent results from studies could be due
to confusion surrounding the diagnosis of IC/PBS. It could also be due to the previously
restrictive diagnostic criteria, which used to isolate patients with very severe,
possibly refractory, disease that may not respond to conservative therapy. Though
no evidence is available to support combination of two or more drugs in the management
of IC, many clinicians combine oral medications in order to enhanced treatment response.
Some patients may show response to one or two drug therapy, but a considerable number
of patients may require all treatment modalities simultaneously. 1,2,4
The advantage of intravesicular drug therapy is that it provides high local drug
concentrations in the bladder. Systemic adverse effects are avoided and problem
of low levels of urinary excretion with orally administered agents is also eliminated.
Dimethyl sulphoxide is the most common FDA-approved agent used for intravesical
therapy. It is sometimes combined with heparin, steroids, bicarbonate and a local
anaesthetic for intravesical administration.1 Bacillus Calmette-Guerin (BCG) has
also been tested in a double-blind, placebo- controlled study in patient with IC.
The results showed a 60% favourable response rate with a 27% placebo response. In
the long term, 89% of patients continued to have symptom improvement, 24 to 33 months
after initial treatment. 3
Commonly Used Drugs in the Management of IC
A recent development in the management of IC is simultaneous use of oral and intravesicular
pentosan ploysulphate. A recently conducted study compared the safety and efficacy
of combination of intravesical and oral PPS and only oral PPS in the treatment of
IC. The combined approach appeared to be a safe and effective therapeutic option
and reduce severity of IC symptoms, thereby, improving the quality of life and well-being.