When you take an antispasmodic like dicyclomine or hyoscine for stomach cramps or irritable bowel syndrome, you might not think about what else you’re taking. But if you’re also on an antihistamine for allergies, a sleep aid, or an antidepressant like amitriptyline, you could be setting yourself up for serious side effects. These medications don’t just work on their own-they interact. And when they do, the results aren’t just inconvenient. They can be dangerous.
What Are Anticholinergic Antispasmodics?
Anticholinergic antispasmodics block acetylcholine, a chemical in your body that tells muscles to contract. By stopping this signal, they relax spasming muscles in your gut, bladder, or airways. Common ones include dicyclomine and hyoscine (also called scopolamine). They’ve been around for decades and are still prescribed for IBS, bladder spasms, and motion sickness.
But here’s the catch: acetylcholine isn’t just in your gut. It’s everywhere-in your brain, your salivary glands, your eyes, your heart. When you block it systemically, you don’t just stop cramps. You also stop saliva production, slow down bowel movements, blur your vision, and speed up your heart. That’s why side effects like dry mouth, constipation, and blurred vision are so common. At higher doses, they can even cause confusion or memory problems, especially in older adults.
Why These Interactions Are So Risky
Anticholinergic drugs don’t just interact with other anticholinergics-they amplify each other. Think of it like turning up the volume on a bad signal. If you take dicyclomine for IBS and diphenhydramine (Benadryl) for allergies, you’re doubling down on the same mechanism. The result? Severe constipation, urinary retention, or even delirium.
A 2023 review in JAMA Internal Medicine found that patients taking two or more anticholinergic medications had a 47% higher risk of cognitive decline over two years. And it’s not just older people. A patient on Reddit shared how combining oxybutynin (for overactive bladder) with Benadryl left them confused and unable to focus for days. That’s not rare. Pharmacists in Edmonton and Toronto report seeing this pattern regularly-patients prescribed by different doctors, unaware they’re stacking anticholinergics.
The American Geriatrics Society Beers Criteria® lists several antispasmodics as potentially inappropriate for adults over 65. Why? Because their bodies process these drugs slower, and their brains are more sensitive to the side effects. One study showed that 69% of patients taking 160 mg of dicyclomine daily had adverse effects-compared to just 16% on placebo.
Medications That Can Make Things Worse
It’s not just other antispasmodics. Many common drugs have hidden anticholinergic effects. Here’s what to watch out for:
- Antidepressants: Amitriptyline, doxepin, paroxetine
- Antipsychotics: Chlorpromazine, olanzapine
- Antihistamines: Diphenhydramine (Benadryl), hydroxyzine, promethazine
- Sleep aids: Doxylamine (Unisom), some melatonin combos
- Bladder medications: Oxybutynin, tolterodine
- Anti-nausea drugs: Promethazine, prochlorperazine
One patient on Drugs.com wrote: “I started amitriptyline for nerve pain and my dicyclomine stopped working. I couldn’t go to the bathroom for five days.” That’s not an isolated case. The Anticholinergic Cognitive Burden Scale, used by doctors since 2023, rates these drugs by how strongly they block acetylcholine. Any combination that scores above 2 is considered high risk.
How to Spot a Dangerous Mix
You don’t need to memorize every drug. But you should know the red flags:
- Unexplained constipation that won’t go away
- Difficulty urinating or feeling like your bladder won’t empty
- Blurred vision, especially when reading or driving
- Feeling unusually confused, foggy, or forgetful
- Rapid heartbeat without exertion
- Dry mouth so bad you can’t swallow
If you’re taking more than one of these drugs, even over-the-counter ones, and you notice any of these, talk to your doctor or pharmacist immediately. Don’t wait. The side effects can build up slowly-you might not realize it’s the meds until it’s too late.
What’s Changing in 2025
Doctors aren’t ignoring this. Since 2022, the University of Washington’s Anticholinergic Burden Calculator has been integrated into major electronic health records. When a provider tries to prescribe dicyclomine to someone already on paroxetine and diphenhydramine, the system flashes a warning. In 12 U.S. health systems, this cut inappropriate prescribing by 43%.
Guidelines have shifted too. The American Gastroenterological Association now recommends non-anticholinergic options as first-line for IBS. That includes peppermint oil capsules, fiber supplements, and low-dose SSRIs like escitalopram, which don’t carry the same interaction risks. In Canada, prescriptions for anticholinergic antispasmodics dropped 22% between 2018 and 2022. Meanwhile, non-anticholinergic alternatives rose by 37%.
Even the packaging has changed. Since January 2023, the European Medicines Agency requires all anticholinergic antispasmodics to carry a clear warning about CNS depressants. In the U.S., the FDA has boxed warnings for use in glaucoma, myasthenia gravis, and with MAO inhibitors.
What to Do If You’re Taking These Medications
Here’s what you can do right now:
- Make a full list of everything you take-prescription, OTC, supplements, herbal remedies. Don’t leave anything out.
- Check each one on the Anticholinergic Burden Scale (available online through the University of Washington). Look for drugs marked as “strong” or “moderate.”
- Bring the list to your doctor or pharmacist. Ask: “Could any of these be interacting?”
- If you’re over 65, ask specifically about the Beers Criteria. Ask if there’s a safer alternative.
- Never stop a medication cold turkey. Some, like amitriptyline, need to be tapered.
One patient in Edmonton told her pharmacist she’d been taking dicyclomine for years and Benadryl every night for sleep. When they switched her to a non-anticholinergic sleep aid and lowered her dicyclomine dose, her confusion cleared up in two weeks. She didn’t even realize the meds were the problem.
The Future: Safer Options Are Coming
Researchers are working on antispasmodics that only act in the gut-without crossing into the brain. Two such drugs are now in Phase III trials. These could be game-changers, especially for older adults. But until they’re available, the safest approach is to use the fewest anticholinergic drugs possible.
For now, if you’re on one, be extra careful. Don’t add another without checking. And if you’re feeling off-confused, constipated, dry-mouthed-don’t assume it’s just aging. It might be your meds talking.
Can I take antispasmodics with over-the-counter sleep aids?
Most over-the-counter sleep aids, like Unisom or Benadryl, contain diphenhydramine or doxylamine-both strong anticholinergics. Combining them with dicyclomine or oxybutynin can cause severe constipation, urinary retention, confusion, or even delirium, especially in older adults. It’s not safe. Look for non-anticholinergic sleep aids like melatonin or magnesium glycinate instead.
Are antispasmodics safe for older adults?
The American Geriatrics Society Beers Criteria® lists several antispasmodics as potentially inappropriate for people over 65. Their bodies process these drugs slower, and their brains are more sensitive to the side effects. Even low doses can cause confusion, falls, or memory loss. If you’re over 65 and taking one, ask your doctor if a non-anticholinergic option like peppermint oil or a low-dose SSRI might work better.
What are the signs of anticholinergic toxicity?
Signs include dry mouth, blurred vision, rapid heartbeat, difficulty urinating, severe constipation, confusion, hallucinations, and memory problems. In extreme cases, it can lead to seizures, coma, or death. If you or someone you know is experiencing multiple of these symptoms while taking antispasmodics or other anticholinergics, seek medical help immediately.
Can I switch from dicyclomine to a safer alternative?
Yes. For IBS, non-anticholinergic options include peppermint oil capsules, fiber supplements like psyllium, low-dose SSRIs (e.g., escitalopram), and gut-directed hypnotherapy. For bladder spasms, mirabegron is a non-anticholinergic alternative. Always talk to your doctor before switching-never stop abruptly.
How do I know if my medication has anticholinergic effects?
Use the Anticholinergic Burden Scale from the University of Washington. It lists 117 common medications and rates them as strong, moderate, or weak anticholinergics. You can also ask your pharmacist to check your list. Many pharmacies now use automated tools that flag risky combinations when you pick up a prescription.