NyQuil vs. ZzzQuil: Is There a Difference?
Written By Kobi Nathan, Pharm.D., M.Ed., CDP, BCGP, AGSF
Sleep Disorders
February 20, 2023

Key Takeaway: ZzzQuil and NyQuil both contain sedating antihistamines. ZzzQuil contains diphenhydramine and NyQuil contains doxylamine, in addition to acetaminophen and dextromethorphan. Both medications are similar in how they work. Use of antihistamines has been linked to an increased risk of Dementia!

When deciding between Zzzquil vs. Nyquil to manage their insomnia or sleep issues, many people are confused about which one is right for them.  In this article, we will explore the main differences between both medications.

I will also highlight a specific warning about using NyQuil and ZzzQuil in older adults.

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Zzzquil and Nyquil contain different antihistamines

Both medications contain antihistamines that are sedating. However, the antihistamines are different in each formulation.

Zzzquil contains diphenhydramine, which is the active ingredient in Benadryl. NyQuill contains doxylamine succinate and two other ingredients.

How do Zzzquil and NyQuil make you sleep?

Both antihistamines help you fall asleep through their sedating effects.

The main way they do this is by blocking a brain chemical called acetylcholine.

The term healthcare providers use to describe this mechanism is “anticholinergic” effects.

Acetylcholine is a neurotransmitter, a chemical messenger. Acetylcholine is important for key bodily functions such as learning, memory, and muscle contractions.

Blocking acetylcholine in your brain can make you sleepy.

NyQuil and ZzzQuil work quickly to help you fall asleep (around 30 minutes) and stay asleep (around 4 to 6 hours).

There are no studies or investigations comparing both antihistamines directly.

Our best guess is that they are similar in potency based on our knowledge of how they work in the brain.

NyQuil has more ingredients than ZzzQuil

ZzzQuil only contains diphenhydramine and is labeled for use solely as a nighttime sleep aid.

On the other hand, NyQuil contains the following ingredients:

  • Doxylamine for sedation
  • Acetaminophen (pain and fever reducer)
  • Dextromethorphan (cough suppressant)

Side effects of NyQuil and Zzz Quil

However, because acetylcholine is important for learning and memory, blocking its effect can have unwanted side effects.

Specifically, it can cause confusion and memory loss due to the abovementioned anticholinergic effects.

This can be especially dangerous for older adults. For people living with Dementia, this can be life-threatening.

You can read about the different types of Dementia, their causes, and treatment in my detailed article here, and the dangers of anticholinergic medications here.

Both antihistamines can cloud your thinking and reflexes. So, use these medications with caution when driving or operating machinery. To avoid daytime drowsiness, try to limit them to only nighttime use.

NqQuil and ZzzQuil use in older adults

Older adults should not use any antihistamines to help them fall asleep. This is because chronic use of anticholinergic drugs in older adults is directly linked to an increased risk of falls, fractures, hospitalization, delirium, confusion, worsening of dementia, and premature death.

The evidence is clear and established, as verified by this often-cited landmark study published in JAMA Internal Medicine.

medication safety and dementia ebook

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The first question I ask my patients in my older adult clinic is if they use any over-the-counter medications containing antihistamines.

If they say yes, I tell them to round them up and throw them in the garbage when they return home.

A better option is melatonin. You can get an inexpensive single-ingredient option here or a combination formulation with magnesium and L-Tryptophan here.

Final Words

Zzzquil and Nyquil are over-the-counter medications that can be used as sleep aids.

ZzzQuil is labeled as a nighttime sleep aid and only contains one ingredient, diphenhydramine.

NyQuill contains doxylamine, an antihistamine, in addition to acetaminophen and dextromethorphan, to treat cough and cold symptoms.

I do not recommend either medication to help with sleep due to the increased risk of over-sedation, falls, fractures, hospitalization, delirium, and dementia in older adults.

A safer option is to take melatonin. My sleep doctor recommends this brand.

Another option is to take magnesium, which is very important for promoting GABA. PerformanceLab, a company I trust, has a good sleep aid that contains three different forms of magnesium:

  1. Magnesium Bisglycinate – a chelated mineral formulation bound with glycine to maximize intestinal absorption.
  2. Magnesium Taurate – Magnesium that is bound to Taurine, an amino acid that promotes GABA.
  3. Nutrigenesis® Magnesium – a clean, probiotic-cultured magnesium complexed with absorption-inducing cofactors.

You can learn more about this product here.

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