NyQuil Bottle image with text - NyQuil with melatonin


There are a variety of Nyquil products currently available over-the-counter, but most contain the following active ingredients:

  • Acetaminophen
  • Dextromethorphan
  • Doxylamine

Acetaminophen is for pain management, dextromethorphan is for cough suppression, and doxylamine is an antihistamine used for sleep, runny nose, sneezing, itching, and watery eyes.

Doxylamine is the ingredient in NyQuil that causes sedation as it is a first-generation antihistamine (similar to Benadryl).

Melatonin is naturally produced in our bodies to help regulate the sleep-wake cycle but is also commonly used over the counter supplement to help treat insomnia.

Online interaction checkers will often list NyQuil products and melatonin as having an interaction with one another due to their additive effects.

This is because both doxylamine and melatonin produce sedation and have mild CNS (central nervous system) depressant properties. Due to this, it is recommended using these products together with caution.


There haven't been any studies that have specifically evaluated the risk of using NyQuil and melatonin together, but based on their known effects, taking both could potentially lead to additive sedation, sleep-related disturbances, CNS and respiratory depression.[1]

If taking these two together, it is important to report any unusual sleep-related behaviors and one of the products may need to be discontinued.

There may be situations where both are recommended, like if you are using melatonin to help treat 'jet lag' (i.e. trying to get your sleep-wake cycle back on your normal schedule) but you should talk to your doctor first before combining.[2]

How Antihistamines Work

Antihistamines bind to histamine receptors that are found in the nose, lungs, eyes, and skin without activating the histamine response. By binding and changing the shape of the histamine receptor, antihistamines inhibit histamine from binding and creating its response.[3]

First-generation antihistamines, like doxylamine, are not selective for any particular tissue and are therefore more likely to cause drowsiness. Both doxylamine and diphenhydramine (Benadryl) are used as an over-the-counter sleep aid in addition to its other uses.

Over time, the body becomes tolerant to the sedative effects of antihistamines and these generally should not be relied upon as a sleep aid for long term use.

How Melatonin Works

Melatonin is naturally produced by the pineal gland and is known to be vital in the circadian rhythm and sleep cycle.[4]

Melatonin production is thought to be stimulated by dark and inhibited by light. It is thought that melatonin helps reset the body to its normal rhythm, especially in patients experiencing jet-lag or who work the night shift.

In the hospital setting, melatonin is sometimes used in the intensive care unit to help promote normal circadian rhythms, reduce delirium and the need for sedatives.


Taking NyQuil products, which contain the sedating antihistamine doxylamine, with melatonin can increase sedation and have additive CNS depressant effects.

  1. ^ Mechanisms by which pharmacologic agents may contribute to fatigue. PubMed
  2. ^ Melatonin for the prevention and treatment of jet lag. PubMed
  3. ^ Elsevier ClinicalKey: Doxylamine Monograph. ClinicalKey
  4. ^ Elsevier ClinicalKey: Melatonin Monograph. ClinicalKey