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Trazodone vs. Benadryl for Sleep—Which One Is Right for You?

Trazodone vs. Benadryl for Sleep—Which One Is Right for You?

In the quest for a good night’s sleep, you may find yourself weighing between different sleep aids. Trazodone and Benadryl are among many potentially helpful options. While both can be effective, they have different properties and are contraindicated for some patients.

This trazodone vs. Benadryl for sleep comparison explains their mechanisms of action, potential side effects, and recommendations for safe use. 

How Does Trazodone Work?

Trazodone is an antidepressant. The medication’s active component is trazodone hydrochloride, which is classified as a serotonin receptor antagonist and reuptake inhibitor. It was approved by the U.S. Federal Drug Administration (FDA) in 1981, and it’s not a controlled substance.

Trazodone works by inhibiting the serotonin reuptake by the brain’s nerves, increasing this neurotransmitter’s levels in the nerve synapse. The drug also reduces the levels of other neurotransmitters that trigger wakefulness, such as:

  • Acetylcholine
  • Noradrenaline
  • Histamine
  • Dopamine

By regulating the release of these neurotransmitters, trazodone promotes feelings of relaxation and drowsiness, contributing to sleep. Recent clinical trials show that patients who took the drug experienced improved sleep efficiency, ratio, and continuity.

The drug is available in six doses:

  1. 10 mg
  2. 20 mg
  3. 50 mg
  4. 100 mg
  5. 150 mg
  6. 300 mg

When using trazodone for sleep problems, you should take it at least an hour before bed so that it kicks in on time.

Who Can Take Trazodone?

Trazodone is generally a safe drug, but it’s not suitable for everyone. Check out the table below for details on who can and can’t use the drug:

Who Should Use Trazodone?

Who Shouldn’t Use Trazodone?

  • Adults (18+)

  • Individuals with major depressive disorder

  • Patients with sleep problems

  • Individuals allergic to trazodone or its components

  • People treated with methylene blue injection

  • Patients who’ve taken MAO inhibitors in the past 14 days

  • Individuals with a recent heart attack or other heart problems

  • Patients with epilepsy or undergoing electroconvulsive treatment 

  • Children 

What Are the Side Effects of Trazodone?

Trazodone carries the risk of side effects, including:

  • Dry mouth
  • Drowsiness
  • Lightheadedness
  • Blurred vision
  • Unusual tiredness or weakness
  • Sweating

Rare adverse reactions to trazodone may include:

  • Skin rash
  • Unusual excitement
  • “Tingling” sensations
  • Confusion about time, place, or identity
  • Muscle tremors
  • Fainting
  • Slow or rapid heartbeat
  • Swelling
  • Shortness of breath

These lists aren’t exhaustive—consult your healthcare provider for more details on the potential side effects of trazodone.

Source: Kampus Production

How Does Benadryl Work?

Benadryl is an antihistamine, with diphenhydramine being its active component. The drug is classified as histamine-H1 antagonist. It was approved for medical use in the U.S. in 1946 and isn’t listed in the DEA’s schedule of controlled substances.

Benadryl blocks histamine-1 (H1) receptors to suppress the release of histamine, a natural hormone your body produces in response to allergies, injuries, or inflammations. The drug alleviates symptoms of allergic reactions, including:

  • Rash
  • Itch
  • Stomach cramps
  • Bronchoconstriction (narrowing of the airways)

The drug also blocks acetylcholine receptors and inhibits the reuptake of serotonin. This combined effect slows down the central nervous system’s (CNS) activity, inducing drowsiness and promoting sleep.

Benadryl has two doses:

  1. 25 mg
  2. 50 mg

The typical starting dose for adults with sleep issues is 50 mg, taken an hour before bedtime. You should dedicate seven hours to sleep when taking this medication to allow it to take full effect and wear off naturally.

Who Can Take Benadryl?

While Benadryl can be effective for sleep, it’s not meant for everyone. You can find a list of who should and shouldn’t take the medication in the table below:

Who Should Use Benadryl?

Who Shouldn’t Use Benadryl?

  • Adults (18+)

  • Children over six years old (they should only use Benadryl as an antihistamine and not for insomnia)

  • Individuals with symptoms of an allergy or cold

  • People experiencing motion sickness

  • Patients with early-stage Parkinsonian syndrome

  • Individuals allergic to diphenhydramine

  • Patients with liver or kidney problems, gastrointestinal blockage, bladder obstruction, or heart disease

  • People with asthma, glaucoma, or thyroid disorder

  • Older adults with a history of urinary retention, constipation, and confusion

What Are the Side Effects of Benadryl?

Benadryl carries the risk of undesired reactions. The most common ones are:

  • Dizziness
  • Dry mouth
  • Blurred vision
  • Daytime drowsiness
  • Constipation

Rare but more concerning side effects of Benadryl include:

  • Tremors
  • Convulsions
  • Paresthesia
  • Vertigo
  • Incoordination
  • Chest tightness

Mild side effects typically diminish after a few days. Contact your doctor immediately if you experience any concerning or persistent unwanted reactions while on Benadryl.

Trazodone vs. Benadryl—Which Is More Effective for Sleep?

Both trazodone and Benadryl can be effective for sleep, but results vary between patients based on their medical history and specific sleep problems. 

Medications alone may not provide a lasting solution for insomnia, so you should visit a specialist to get comprehensive treatment. But with the acute shortage of doctors specializing in sleep medicine in the U.S., getting an appointment with an expert isn’t a walk in the park. 

The good news is that with the rapid rise of telemedicine platforms, you no longer have to endure the grueling wait. Kick, an online performance medicine clinic, lets you consult specialists from the comfort of your home.

Source: Andrea Piacquadio

Kick—Better Sleep, Better Performance

Designed by a Stanford sleep expert, Dr. Alex Dimitriu, Kick’s sleep program combines pharmaceutical and non-pharmaceutical methods to help you get holistic treatment. When you join the program, our expert will:

  • Analyze your medical information and prescribe two trial medications based on your profile
  • Schedule regular consultations to monitor your progress
  • Offer tips on developing healthy sleep hygiene
  • Personalize the treatment further if necessary

Kick’s personalized approach has proven highly effective, as evidenced by glowing reviews on Trustpilot by our patients.

How To Join Kick

To revitalize your sleep with Kick, follow these easy steps:

  1. Go to the signup page to start your brief sleep visit
  2. Fill out the medical questionnaire to help us understand your health status and sleep history
  3. Choose between home or local pharmacy delivery for receiving your medication

Our team will design a tailored plan within 24 hours, helping you begin treatment immediately. If our experts decide that you’re not the best candidate for Kick, you won’t pay for the initial consultation, according to our Doctor Guarantee.

Source: PNW Production

Benadryl vs. Trazodone—Potential Interactions With Other Substances

Trazodone and Benadryl may interact with other medications, as outlined in the table below:

Medication Category


Interaction With Trazodone

Interaction With Benadryl



Can raise the risk of respiratory depression or interfere with the potency of anticonvulsants

Can contribute to the risk of seizures



Can add to the risk of serotonin syndrome

Can enhance the risk of excessive sleepiness


Zyrtec (cetirizine), doxylamine, hydroxyzine

The potential for interaction with most antihistamines is low, but taking trazodone with doxylamine or hydroxyzine can raise the risk of unwanted reactions

Can add to the risk of side effects



Can raise the risks of low blood pressure and beta-blocker overdose

Can contribute to low blood pressure

CNS depressants


Can enhance the risk of dizziness, drowsiness, and serotonin syndrome

Can contribute to drowsiness

Dietary supplements

St. John’s wort

St. John’s wort can contribute to sedation

St John’s wort can enhance the risk of dizziness



Can add to the risk of dizziness and drowsiness

Can enhance the sedative effects

Muscle relaxants

Cyclobenzaprine, Robaxin, metaxalone

Can add to the sedative effects

Can raise the risk of severe sedation

Non-steroidal anti-inflammatory drugs (NSAIDs)

Ibuprofen, Diclofenac, Naproxen

Can raise the risk of bleeding

The potential for interaction is low, but risks can’t be disregarded

Sleep or anxiety medications and supplements

Belsomra, Dayvigo, Doxepin, melatonin, mirtazapine

Can enhance the sedative effects

Can raise the risk of severe drowsiness

Trazodone and Benadryl for Sleep—Alternatives

Source: Yan Krukau

If the risks of using trazodone and Benadryl outweigh the benefits, your doctor may recommend other sleep aids. Check out the table below for details on when your healthcare may recommend each alternative:


When Your Doctor May Recommend It

Common Side Effects


You have irregular sleep-wake cycles

  • Headache

  • Dizziness

  • Nausea


You have sleep onset or sleep maintenance issues

  • Daytime drowsiness

  • Dizziness

  • Fatigue


You have primary insomnia

  • Drowsiness

  • Headache 

  • Unusual dreams


You have sleep issues caused by muscle tension or injury

  • Drowsiness

  • Dry mouth

  • Headache


You have occasional sleeplessness due to the symptoms of allergic reactions

  • Drowsiness 

  • Dizziness

  • Dry mouth


You experience sleeplessness due to pain

  • Nausea

  • Constipation

  • Dizziness


You have insomnia caused by anxiety or major depressive disorder

  • Drowsiness

  • Dry mouth

  • Weight gain


You have occasional sleep issues, especially due to restless leg syndrome (RLS)

  • Drowsiness

  • Dizziness

  • Dry mouth


You have sleepless nights due to mood conditions

  • Drowsiness

  • Dry mouth

  • Dizziness


You have sleep problems caused by anxiety or depression

  • Dizziness

  • Drowsiness

  • Dry mouth


You have occasional sleep issues

  • Dry mouth

  • Confusion

  • Constipation


You have insomnia due to anxiety

  • Headache

  • Irritability

  • Difficulty concentrating


You have sleepless nights due to anxiety or migraines

  • Dizziness

  • Difficulty breathing

  • Chesty cough


You have sleep problems caused by anxiety

  • Drowsiness

  • Blurred vision

  • Dry mouth


You have insomnia due to anxiety or major depressive disorder

  • Dry mouth

  • Nausea

  • Dizziness

These are general recommendations—your prescription may vary depending on your medical history and specific sleep problems. To avoid unwanted reactions or interactions, you should only switch between these medications under the guidance of your doctor.

For more information on these drugs, consult your healthcare provider.

Featured image source: Kebs Visuals