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Key takeaways
Trazodone and Benadryl are both sedating and can cause extreme and potentially dangerous drowsiness if taken together.
If you take both, stay in a safe environment and have someone you trust on hand to monitor you for any concerning symptoms.
If you’ve historically used one or both of these medications, consider alternative medications and lifestyle strategies for sleep issues, allergy relief, or both.
Picture this: You’ve lived with insomnia for years, finally finding some much-needed rest with the help of trazodone, an antidepressant prescribed off-label as a sleep aid. But now allergy season has arrived, and the only medicine that consistently provides relief is Benadryl (diphenhydramine). Can you take Benadryl if you’re already taking trazodone, either for insomnia or for depression? Read on to find out, plus discover some alternative strategies for sleep and allergy relief.
Can you take Benadryl with trazodone?
“There are isolated occasions where a person might find themselves considering taking both Benadryl and trazodone, but it is not recommended,” says Carrie Kreps, Pharm.D., the director of clinical services at Pharmacy Care Associates, an independent specialty retail pharmacy in Montgomery, Alabama. “Both agents can be very sedating, and the combination could be quite problematic.” In other words, both Benadryl and trazodone make you drowsy, so taking them together is likely to amplify this side effect and the potential risks that can accompany it.
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Potential dangers and side effects when combining Benadryl and trazodone
Taking Benadryl and trazodone together can be dangerous for anyone, but certain people have an increased risk of adverse effects. “Older adults, people with breathing issues or neurological conditions, or those using other sedating medications or alcohol are at even higher risk,” says Kara Wada, MD, an allergist-immunologist and lifestyle medicine provider.
These are the most notable drug interactions.
1. Severe drowsiness
The most dangerous side effect of combining trazodone and Benadryl is sedation. “Both medications enhance central nervous system depression, reduce alertness, and slow reaction time,” Dr. Wada explains. “Diphenhydramine crosses the blood-brain barrier and causes sedation through antihistamine effects.” Trazodone works by changing serotonin levels in the brain, which can cause sleepiness.
2. Increased risk of falls or accidents
“Any medication that causes drowsiness on its own increases the risk of falls and accidents because of reduced alertness,” Dr. Kreps says. Put two of them together, such as Benadryl and trazodone, and this risk only increases further. Dr. Kreps adds that Benadryl is anticholinergic, which means it blocks the activity of the neurotransmitter acetylcholine. Some of the most common side effects of anticholinergic drugs include blurred vision, confusion, and reduced muscle strength, all of which can contribute to a higher likelihood of falls.
3. Impaired cognitive function
While low doses of trazodone don’t tend to impair cognitive function or cause brain fog, Dr. Kreps says that Benadryl is known to have a “hangover effect,” especially in people older than 65. “This is where the residual effects of the drug linger through the morning and midday the next day, reducing attention span and resulting in a foggy-headed sensation,” she explains. Add in the drowsiness factor from the trazodone, and it could be difficult to focus.
What’s more, a study published in JAMA Internal Medicine found a link between exposure to anticholinergic drugs and an increased risk of dementia, suggesting that using Benadryl on a regular basis in the long-term may also contribute to cognitive issues.
RELATED: Does Benadryl raise your blood pressure?
What to do if you’ve accidentally taken trazodone with Benadryl
If you accidentally take Benadryl and trazodone together, or you find yourself in a situation where you need both close together, Dr. Wada says the most important thing to do is to stay in a safe environment. “You should not drive or operate machinery and skip any other substances that may be sedative, like alcohol,” she adds. If you do take both at the same time, Drs. Kreps and Wada suggest having someone you trust keep an eye on you to monitor for symptoms like difficulty staying awake (if it’s daytime), slowed or shallow breathing, confusion, or unusual behavior. “If concerning symptoms develop, seek emergency care or contact Poison Control,” Dr. Wada says.
If you must take both, Dr. Kreps recommends trying to separate the two drugs by about six hours. “A possible scenario might look like this: A patient who takes trazodone nightly for insomnia gets stung by a bee, and they are highly allergic,” Dr. Kreps posits. “If a dose of Benadryl has historically been effective for the bee sting, I would suggest either skipping the bedtime dose of trazodone for that night or at least separating the two medications by six hours.” Ask your prescribing healthcare provider for guidance specific to you and any preexisting health conditions you have that might affect the timing of these medications.
Safer alternatives and strategies for sleep or allergy relief
While trazodone is often prescribed for insomnia, Dr. Kreps notes that it was not originally intended to treat sleep issues. Trazodone is FDA approved to treat major depressive disorders only and is used off-label for insomnia. Even though it tends to be well-tolerated and effective, there are plenty of lifestyle strategies that may help improve your sleep without worrying about the potential side effects of trazodone. Dr. Kreps and Dr. Wada suggest trying the following:
- Setting a consistent sleep/wake schedule
- Getting natural light exposure in the morning and avoiding blue light from screens for one to two hours before bed
- Limiting caffeine intake in the afternoon and evening
- Limiting alcohol before bed
- Using relaxation techniques such as mindfulness or meditation
- Trying cognitive behavioral therapy for insomnia (CBT-I)
- Taking over-the-counter supplements such as magnesium glycinate, magnesium threonate, or melatonin
- Asking your provider about alternatives to treat insomnia, such as hydroxyzine, an antihistamine that could improve allergies and sleep
RELATED: Hydroxyzine vs. Benadryl
There are also many other medications and lifestyle strategies that can provide allergy relief without the potential side effects of Benadryl. “Benadryl can be helpful for acute (urgent) allergic reactions, but I do not like this product to treat seasonal or environmental allergies on a routine basis,” Dr. Kreps says. Instead, Drs. Kreps and Wada suggest considering the following alternative medications:
- Newer generation antihistamines, such as Claritin (loratadine), Zyrtec (cetirizine), and Allegra (fexofenadine)
- Intranasal steroids, such as Flonase (fluticasone)
- Intranasal antihistamines, such as Astepro (azelastine)
- Mast cell stabilizer nose spray or eye drops, such as NasalCrom (cromolyn) or ketotifen
- Eye drops for ocular symptoms, such as Pataday (olopatadine)
- Nasal saline rinses
- Xylitol nasal spray
- Allergy immunotherapy, such as shots, drops, or lymph node injections
You can also use the following lifestyle modifications:
- Running HEPA air purifiers, especially in the bedroom
- Showering and/or changing clothes after being outdoors
- Identifying and avoiding key triggers
The bottom line
Experts agree that you should avoid taking trazodone and Benadryl together whenever possible. These two medications can cause extreme drowsiness and sedation, which can be dangerous and require monitoring. If you have been prescribed trazodone for insomnia or depression and anticipate situations in which you have traditionally relied on Benadryl, it’s important to seek medical advice from a healthcare professional to determine the safest course of action should one of these situations arise.
Frequently asked questions about trazodone and Benadryl
Can I take trazodone and Benadryl together for sleep?
You shouldn’t take trazodone and Benadryl together for sleep. Benadryl and trazodone cause drowsiness on their own, so taking them together is likely to increase drowsiness and the potential risks that come with it.
What can I take instead of Benadryl for itching?
Newer-generation antihistamines, such as Claritin (loratadine), Zyrtec (cetirizine), and Allegra (fexofenadine), are less likely than Benadryl to cause drowsiness and can help relieve itching from allergic reactions, hives, and insect bites. Your healthcare provider can provide specific guidance while considering any other medications you may be taking.
What can I take instead of trazodone for sleep?
Lifestyle adjustments like setting a consistent sleep schedule, avoiding blue light from screens for one to two hours before bed, and limiting caffeine and alcohol intake can improve sleep. You can also ask your healthcare provider about medications such as hydroxyzine, an antihistamine that can improve sleep and relieve allergy symptoms. Ambien, a well-known sleep aid, should not be combined with Benadryl.
- Anticholinergic drugs, Cleveland Clinic (2024)
- Anticholinergic drug exposure and the risk of dementia: A nested case-control study, JAMA Internal Medicine (2019)
- Trazodone, National Library of Medicine (2024)