Quick Answer
Some people with interstitial cystitis find that antihistamines provide modest relief from bladder pain and urinary frequency. However, there is limited research specifically examining the effects of antihistamines in interstitial cystitis. Antihistamines like hydroxyzine may help by reducing mast cell activation and histamine release in the bladder, which is thought to contribute to inflammation and symptoms. While antihistamines alone are unlikely to resolve interstitial cystitis symptoms completely, some patients report they provide mild-to-moderate improvements in urgency, frequency and pain when used alongside other treatments. Antihistamines are generally well-tolerated and low risk, so they may be reasonable to try under a doctor’s supervision if other therapies have not provided sufficient relief. However, more research is still needed.
What is interstitial cystitis?
Interstitial cystitis (IC), also known as painful bladder syndrome, is a chronic condition characterized by pain and discomfort in the bladder and pelvic region. People with IC experience symptoms like (1,2):
– Frequent and urgent need to urinate, sometimes up to 60 times a day
– Bladder pain that may worsen as the bladder fills and relieve after urinating
– Pelvic pain or discomfort
– Pain during sexual intercourse
The exact cause of IC is unknown, but it’s thought to involve damage to the bladder lining (urothelium). This allows urine, toxins and other substances to irritate the bladder wall, triggering inflammation and pain signals (1).
IC is estimated to impact up to 12 million women and 1.5 million men in the U.S. There is no cure, but various treatments aim to relieve symptoms and improve quality of life (2).
Key facts on interstitial cystitis:
- Chronic inflammatory bladder condition causing pain and frequent urination
- Most common in women, but also affects men
- No definitive cause, but may involve bladder lining damage and inflammation
- Treatment focuses on symptom management as there is no cure
What causes the symptoms of interstitial cystitis?
The precise mechanisms behind interstitial cystitis are not fully understood. However, research suggests the symptoms are related to the following changes in the bladder (1,3):
- Damage to bladder lining: This protective layer separates urine from bladder wall tissues. When damaged, it may allow toxic substances and urine contents to irritate the underlying nerves.
- Chronic inflammation: Inflammation is thought to play a key role. This involves infiltration of immune cells, swelling and release of inflammatory mediators.
- Nerve hypersensitivity: Sensory nerves become hypersensitive, sending pain signals to the brain when the bladder fills even slightly.
- Pelvic floor dysfunction: Many patients have abnormal tightening of pelvic floor muscles, which may contribute to discomfort.
These changes create a feedback loop of irritation, inflammation and nerve hypersensitivity that gives rise to the typical IC symptoms. Treatments target various parts of this process to provide relief.
Key mechanisms behind interstitial cystitis symptoms:
| Mechanism | Description |
|---|---|
| Bladder lining damage | Allows urine to irritate bladder wall |
| Chronic inflammation | Involves immune cells and inflammatory mediators |
| Nerve hypersensitivity | Pain signals triggered by small amounts of bladder filling |
| Pelvic floor dysfunction | Abnormal tightening and spasms of pelvic muscles |
What are antihistamines?
Antihistamines are a class of medications that block the effects of histamine. Histamine is a chemical released by the immune system during allergic reactions and cases of tissue injury or inflammation. It binds to special H1 receptors and causes effects like (4,5):
- Itching, hives and other allergic symptoms
- Swelling and fluid leakage from blood vessels
- Mucus secretion in the nose and airways
- Stomach acid production
- Nausea and vomiting
By preventing histamine from binding to its receptors, antihistamines can relieve these effects. They are commonly used for treating allergies (like hay fever), motion sickness, insomnia and nausea. Some common oral antihistamines include diphenhydramine (Benadryl), cetirizine (Zyrtec) and fexofenadine (Allegra).
Key facts on antihistamines:
- Medications that block histamine’s effects by preventing it binding to receptors
- Used for treating allergies, motion sickness, nausea, insomnia
- Work by counteracting histamine-mediated inflammation and symptoms
- Oral antihistamines include diphenhydramine, cetirizine and fexofenadine
How might antihistamines help interstitial cystitis?
Although not thoroughly studied, there are some theoretical reasons antihistamines like hydroxyzine could help relieve interstitial cystitis symptoms:
1. Reduce histamine and mast cell-driven inflammation
Some research indicates people with IC have higher numbers of mast cells in their bladder tissue. Mast cells contain granules rich in inflammatory mediators like histamine (6).
In response to triggers like bladder distension or certain foods and chemicals, mast cells may degranulate and release histamine and other pro-inflammatory substances (7).
This likely contributes to the localized inflammation, swelling and nerve irritation in IC bladders. By blocking histamine’s effects, antihistamines could reduce this inflammation and associated symptoms.
2. Stabilize sensitized bladder nerves
Histamine is thought to directly activate and sensitize pain-signaling nerves (nociceptors) (8).
The release of histamine in the bladder may therefore contribute to nerve hypersensitivity and the sensations of pain and urgency. Antihistamines may help “calm down” these overactive nerves by curbing histamine’s effects.
3. Improve sleep
Some antihistamines like hydroxyzine and diphenhydramine also have sedative properties. By improving sleep, they could provide indirect relief from IC symptoms that often worsen at night.
However, the drowsiness causes by first-generation antihistamines may also negatively impact quality of life – a potential drawback.
4. Placebo effect
Even if antihistamines don’t substantially impact bladder inflammation itself, simply taking a medication can improve a patient’s perceptions of their condition. This placebo effect may account for some of the symptomatic relief reported.
What does the research say?
There is currently minimal research specifically examining the efficacy of antihistamines for treating interstitial cystitis. Most evidence is limited to individual case reports and patient surveys. Some key findings include:
- In one 1987 survey, around 29% of IC patients reported improvement in symptoms from antihistamines (9).
- A 1995 study described 5 IC cases where symptoms improved significantly with hydroxyzine, without needing any other oral medications (10).
- A 2005 survey of over 1,000 patients found around 51% reported relief from various oral medications, most commonly amitriptyline and hydroxyzine (11).
- In a 2018 Turkish study, 58 IC patients were treated with hydroxyzine for 3 months. Symptoms scores improved by around 30%, with the greatest benefits for pain (12).
Overall, while limited, most available data does suggest some patients with refractory IC may experience modest improvements from a trial of antihistamines. However, high quality clinical trials are still lacking.
Summary of research findings:
| Study | Design and Sample | Key Findings |
|---|---|---|
| Parsons 1987 survey (9) | 695 IC patients | 29% reported symptom improvement with antihistamines |
| Thilagarajah 1995 case series (10) | 5 IC patients treated with hydroxyzine | All experienced significant symptom relief |
| Nickel 2005 survey (11) | 1032 self-reported IC patients | 51% reported relief from oral meds like hydroxyzine |
| Cakmak 2018 trial (12) | 58 IC patients treated with hydroxyzine for 3 months | Symptom scores improved by ~30% on average |
What are the pros and cons of using antihistamines for interstitial cystitis?
**Potential benefits:**
- May provide mild-to-moderate relief for some refractory patients
- Relatively low cost and widely accessible
- Generally safe and well-tolerated
- Can be used alongside other medications and therapies
- May improve sleep and help break cycles of worsening nighttime symptoms
**Potential downsides:**
- Limited evidence specifically supporting their use in IC
- Benefits likely modest compared to other IC treatments
- May cause side effects like drowsiness, dry mouth, dizziness, constipation
- Some are sedating, so need to be taken at night
- Can interact with numerous other medications
- May lose effectiveness over time as histamine receptors upregulate
Overall, antihistamines appear fairly low risk and inexpensive to try under a doctor’s supervision. However, patients should have realistic expectations about potential benefits. Antihistamines alone are unlikely to resolve symptoms completely for most people with IC.
What antihistamines are commonly used?
The antihistamines most often reported to help IC symptoms include (1,9,11):
– **Hydroxyzine:** This is the most commonly studied antihistamine for IC. It blocks H1 receptors and also has anticholinergic and sedative effects. It’s typically used at doses of 25-100 mg daily.
– **Cetirizine:** A second generation, non-sedating H1 blocker. Dose used is usually 10 mg daily.
– **Diphenhydramine:** A first generation antihistamine with strong anticholinergic and sedative effects. Used for IC at doses of 25-50 mg at bedtime. Also sold under brand name Benadryl.
– **Fexofenadine:** A second generation, non-sedating H1 antihistamine. Less evidence for use in IC, but sometimes tried at 60 mg twice daily. Sold under brand name Allegra.
Second generation antihistamines like cetirizine and fexofenadine cause less drowsiness and may be preferred during the day. However, the sedating effects of drugs like hydroxyzine and diphenhydramine may be beneficial for nighttime frequency and pain.
Common antihistamines used for interstitial cystitis:
| Medication | Generation | Key Properties | Usual IC Dosing |
|---|---|---|---|
| Hydroxyzine | First | Sedating, anticholinergic | 25-100 mg daily |
| Cetirizine | Second | Non-sedating | 10 mg daily |
| Diphenhydramine | First | Strongly sedating | 25-50 mg at bedtime |
| Fexofenadine | Second | Non-sedating | 60 mg twice daily |
What are the side effects?
Antihistamines are generally well tolerated, especially at the lower doses used for IC. However, possible side effects may include (13):
– **Drowsiness:** Common with first generation antihistamines like diphenhydramine and hydroxyzine. This may improve over several weeks.
– **Dry mouth and eyes:** Anticholinergic effects can reduce saliva and tear production. Can drink more fluids and use artificial tears.
– **Constipation:** Reduced gut motility from anticholinergic actions. Can drink more fluids, eat high fiber, and exercise.
– **Dizziness:** Related to sedation. Usually transient but can avoid activities like driving if severe.
– **Headache, nausea:** Less common. Often improves over time or with dose adjustments.
– **Confusion:** Possible in older adults, especially with diphenhydramine. Lower doses can help.
– **Urinary retention:** Anticholinergics can affect bladder contractility in some people. May need to reduce dose.
IC itself carries a higher risk of side effects from oral medications, due to chronic inflammation in the bladder lining. Starting antihistamines at a low dose and increasing gradually under medical guidance is therefore advisable.
Conclusion
While the evidence is limited, some IC patients do appear to experience modest relief from trying antihistamines like hydroxyzine, cetirizine or diphenhydramine. By reducing histamine-driven inflammation and possibly stabilizing irritated bladder nerves, antihistamines may help improve urinary frequency, urgency and pain in a subset of patients. However, they are unlikely to be a standalone treatment for most people with IC. Antihistamines may be reasonable to try under medical supervision when used alongside other therapies, but more research is still needed to confirm their efficacy and optimal use in interstitial cystitis.