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Diphenhydramine vs. Doxylamine: What's the Difference?

Edited by Janet White || By Harlon Moss || Published on January 13, 2024
Diphenhydramine and doxylamine are both antihistamines used as sleep aids, but they have different chemical structures and side effect profiles.

Key Differences

Diphenhydramine and doxylamine are both first-generation antihistamines commonly used to treat allergy symptoms and as sleep aids. Diphenhydramine, available over the counter, is known for its efficacy in reducing allergic reactions and inducing drowsiness. Doxylamine, also an over-the-counter medication, shares these effects but has a slightly different chemical structure.
In terms of side effects, diphenhydramine can cause drowsiness, dizziness, and dry mouth. It's often chosen for its sedative properties, making it useful as a sleep aid. Doxylamine can also cause similar side effects, but some users report more pronounced dry mouth and morning grogginess. This difference can be attributed to its slightly longer half-life.
Regarding their use as sleep aids, diphenhydramine is a common ingredient in many over-the-counter sleep products. It works by blocking histamine receptors, which helps induce sleep. Doxylamine, found in products like Unisom, also works by blocking histamine receptors, but its effectiveness and duration can vary slightly from person to person compared to diphenhydramine.
In terms of allergies, diphenhydramine is often the go-to choice for immediate relief from allergic symptoms like runny nose, itching, or hives. Doxylamine, while effective, is less commonly used for allergies and more for its sedative properties in aiding sleep.
The duration of action varies slightly between the two. Diphenhydramine typically has a shorter duration of action, requiring more frequent dosing. Doxylamine, with a longer half-life, can provide longer-lasting relief but may also result in more prolonged side effects, such as next-day drowsiness.

Comparison Chart

Chemical Structure

Different from doxylamine
Different from diphenhydramine

Primary Use

Allergies, sleep aid
Primarily as sleep aid

Side Effects

Drowsiness, dizziness, dry mouth
More pronounced dry mouth


Shorter, requires frequent dosing
Longer, more prolonged effects

Common Formulations

Many OTC allergy and sleep products
Often in sleep-specific products

Diphenhydramine and Doxylamine Definitions


Can cause side effects like drowsiness and dry mouth.
After taking diphenhydramine, he felt sleepy and had a dry mouth.


Has a longer half-life compared to diphenhydramine.
Due to its longer half-life, doxylamine provided all-night relief.


An antihistamine used to treat allergies and as a sleep aid.
She took diphenhydramine to alleviate her hay fever symptoms.


Can cause side effects like morning grogginess and dry mouth.
She experienced morning grogginess after using doxylamine.


Available over the counter in various forms, including tablets and liquids.
She bought diphenhydramine in liquid form for easier consumption.


Blocks histamine receptors, aiding in sleep induction.
Doxylamine's effectiveness in blocking histamine helped her sleep better.


A medication that blocks histamine receptors in the body.
Diphenhydramine helped reduce his allergic reaction quickly.


Found in over-the-counter sleep products like Unisom.
He purchased doxylamine-containing Unisom for his sleep issues.


Often used to treat motion sickness and insomnia.
For her long flight, she packed diphenhydramine to prevent motion sickness.


An antihistamine primarily used as a sleep aid.
He took doxylamine to help with his insomnia.


A sedating antihistamine drug, C17H21NO, used usually in the form of its hydrochloride to treat symptoms of colds and allergic conditions, motion sickness, insomnia, and parkinsonism.


(pharmaceutical drug) An antihistamine derived from pyridine that is typically used in the form of its succinate C17H22N2O·C4H6O4 to treat respiratory symptoms of the common cold and allergies, to induce sleep in the treatment of insomnia, and in combination with pyridoxine hydrochloride to control nausea and vomiting associated with pregnancy.


(pharmaceutical drug) An antihistamine and anticholinergic drug that blocks the effect of histamine at H1 receptor sites, relieving allergy symptoms. It also reduces smooth muscle contraction, increases heart rate, and sedates the user by blocking muscarinic acetylcholine receptors (mAChRs).
Diphenhydramine is a convenient and cheap antihistamine for use, but there are other drugs that do not make the user tired.


Antihistamine (trade name Benadryl) used to treat allergic reactions involving the nasal passages (hay fever) and also to treat motion sickness


How often should diphenhydramine be taken?

Depending on the need, often at night for sleep.

What is diphenhydramine primarily used for?

Treating allergies and as a sleep aid.

What are the common uses of doxylamine?

Primarily as a sleep aid.

How long does doxylamine last?

It has a longer duration due to its longer half-life.

Is doxylamine effective for allergies?

It's less commonly used for allergies.

Can diphenhydramine cause drowsiness?

Yes, it's a common side effect.

What forms does doxylamine come in?

Mainly in tablets, often in sleep aids.

Can doxylamine be used during pregnancy?

It's best to consult a doctor before using during pregnancy.

How does diphenhydramine work?

By blocking histamine receptors in the body.

Can doxylamine cause morning grogginess?

Yes, due to its longer half-life.

Is diphenhydramine available OTC?

Yes, in various forms like tablets and liquids.

Is diphenhydramine safe for children?

It should be used with caution and under medical advice for children.

Are there any non-sleep related uses for doxylamine?

It's less commonly used for non-sleep purposes.

Can diphenhydramine interact with other medications?

Yes, it can interact with other drugs; consult a healthcare provider.

Can I use doxylamine for a cold?

It's not typically used for cold symptoms.

Can diphenhydramine treat motion sickness?

Yes, it's effective against motion sickness.

What's the difference in side effects between these two?

Doxylamine may cause more pronounced dry mouth and grogginess.

What should I do if I experience severe side effects from diphenhydramine?

Seek medical attention immediately.

Can either be habit-forming?

Long-term use can lead to dependence; short-term use is recommended.

Is doxylamine suitable for long-term use?

It's generally recommended for short-term use.
About Author
Written by
Harlon Moss
Harlon is a seasoned quality moderator and accomplished content writer for Difference Wiki. An alumnus of the prestigious University of California, he earned his degree in Computer Science. Leveraging his academic background, Harlon brings a meticulous and informed perspective to his work, ensuring content accuracy and excellence.
Edited by
Janet White
Janet White has been an esteemed writer and blogger for Difference Wiki. Holding a Master's degree in Science and Medical Journalism from the prestigious Boston University, she has consistently demonstrated her expertise and passion for her field. When she's not immersed in her work, Janet relishes her time exercising, delving into a good book, and cherishing moments with friends and family.

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