ZzzQuil Ultra Vs. 'Regular' ZzzQuil
In our latest question and answer, the pharmacist compares two ZzzQuil products, ZzzQuil Ultra and ZzzQuil.

Question
I saw a commercial for ZzzQuil Ultra tabs and I am wondering how it is different than regular ZzzQuil. I currently use the regular ZzzQuil and it works fine, but I'd be interested to know if the Ultra is better.

Answered by Dr. Brian Staiger, PharmD
Medical Content Reviewed By HelloPharmacist
Staff
Last updated Apr 18, 2025
Key points
- ZzzQuil Ultra and 'regular' ZzzQuil contain different active ingredients.
- ZzzQuil Ultra contains doxylamine, while ZzzQuil contains diphenhydramine.
- Doxylamine and diphenhydramine are very similar antihistamines. Both are classified as 'first-generation' and are generally sedating.
- Studies show that diphenhydramine tends to work a little faster than doxylamine, but doesn't last quite as long.
Hello and thank you for your question!
Very simply, the difference between the two products (ZzzQuil Ultra and ZzzQuil) is the active ingredient:
- ZzzQuil Ultra contains doxylamine 25mg per tablet
- 'Regular' ZzzQuil contains diphenhydramine 25 mg per liquicap
Both doxylamine and diphenhydramine are sedating antihistamines, which is why they are used in these types of products to help you fall asleep.
As for the difference between the two active ingredients, I'll touch on that in the next sections.
ZzzQuil Products
There are a number of different ZzzQuil products on the market, so below, I've included a handy chart showing each, along with their active ingredient and recommended dose.
Product | Active Ingredient(s) | Recommended Usage |
---|---|---|
ZzzQuil Ultra Tablets | Doxylamine 25mg (per tablet) | Adults & children 12 yrs & over: One tablet 30 minutes before going to bed |
ZzzQuil Liquicaps | Diphenhydramine 25mg (per tablet) | Adults & children 12 yrs & over: Two LiquiCaps at bedtime |
ZzzQuil Warming Berry Liquid | Diphenhydramine 50mg/30mL | Adults & children 12 yrs & over: 30 mL at bedtime |
ZzzQuil Night Pain Liquid | Diphenhydramine 50mg/30mL Acetaminophen 1,000mg/30mL | Adults & children 12 yrs & over: 30 mL at bedtime |
ZzzQuil Night Pain GelTabs | Diphenhydramine 25mg (per tablet) Acetaminophen 500mg (per tablet) | Adults & children 12 yrs & over: Two geltabs at bedtime |
Closely Related Antihistamines
So, to reiterate, the main difference between the new ZzzQuil Ultra and the original ZzzQuil is the active ingredient (doxylamine vs. diphenhydramine).
These are both very similar antihistamines, and you've likely seen or even used them in different products.
For example, diphenhydramine is the active ingredient in Benadryl, and doxylamine is used as the active ingredient in Unisom.
How Are Antihistamines Classified?
Now, antihistamines, as a drug class, are divided/sorted in a few ways.
Sometimes they are referred to by a 'generation' (first-generation antihistamines cross the blood-brain barrier and tend to cause sedation, while second-generation antihistamines cross only to a minor degree and are generally nonsedating).
Additionally, antihistamines are divided up into chemical groups, based on their chemical structure (e.g. ethanolamines, alkylamines, piperazines).
Both doxylamine and diphenhydramine are considered first-generation antihistamines and are in the same chemical group (ethanolamines).
Comparison
There are very few studies that directly compare doxylamine and diphenhydramine to one other in regard to how well they work for helping someone fall/stay asleep.
What we do know, based on the properties of each drug, is that doxylamine, in general, lasts slightly longer than diphenhydramine does.
This is based on the known 'half-life' of each drug (i.e. how long it takes for 50% of a drug to be metabolized by the body).
While studies report slightly different values, diphenhydramine has a reported half-life between 2 and 8 hours, while the reported half-life for doxylamine is between 8 and 15 hours (most often reported to be around 10-12 hours).
Additionally, studies show that diphenhydramine absorbs a little faster into the bloodstream than doxylamine.
It takes around 1.5 hours for diphenhydramine to reach maximum blood levels while doxylamine reportedly takes around 1.5 to 2.5 hours (depending on which source you refer to). In practice, diphenhydramine tends to work faster than doxylamine does.
Final Words
Overall, these are two very similar antihistamines.
It's not uncommon that an individual may respond better to one or the other.
As a broad generalization, diphenhydramine tends to work a little faster than doxylamine, but doesn't last quite as long.
Thanks again for your question and be sure to reach out to us again in the future!
References
- H1 Antihistamines: Current Status and Future Directions, PubMed
- ZzzQuil Manufacturer Website, ZzzQuil.com
- Over-the-counter medications containing diphenhydramine and doxylamine used by older adults to improve sleep, PubMed
- Over-the-Counter Agents for the Treatment of Occasional Disturbed Sleep or Transient Insomnia: A Systematic Review of Efficacy and Safety, PubMed
- Clearance of the antihistamine doxylamine. Reduced in elderly men but not in elderly women, PubMed
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Dr. Brian Staiger, PharmD
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