Zoloft With Unisom Interaction Details

In our latest question and answer, the pharmacist discusses the safety of combining Zoloft and Unisom.


I have taken 25mg of Zoloft for 3 days at around noon, and tonight I took a Unisom sleep gels to fall asleep. Is it safe to take Unisom while on Zoloft?

Asked by Mok On Mar 11, 2023

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Mar 13, 2023
Last updated Mar 13, 2023

Key points

  • There are several different Unisom products on the market. Most contain either diphenhydramine or doxylamine, both sedating antihistamines.
  • Zoloft doesn't specifically interact with Unisom products, but there is a chance of certain additive effects, like drowsiness.

Quick Answer

Unisom is a brand name product, and there are several different formulations containing different active ingredients (e.g., Unisom SleepGels contain diphenhydramine while Unisom SleepTabs contain doxylamine). Zoloft doesn't specifically interact with either of these Unisom products but there is a risk of certain additive side effects (e.g., drowsiness, dizziness).

Detailed Answer

As mentioned, there are several different 'Unisom' products on the market.

Although there are 'drug-free' Unisom products, when Unisom is brought up in the context of a drug interaction question like this, generally what is being referred to are the Unisom products that contain one of two sedating antihistamines:

  • Diphenhydramine
  • Doxylamine

Diphenhydramine is a commonly utilized sedating antihistamine available in a number of different products, including Benadryl and Unisom SleepGels.

Doxylamine is also a sedating antihistamine and can be found in products like NyQuil and Unisom SleepTabs.

Regardless of which Unisom product you are referring to, we are looking for an interaction between a sedating antihistamine and Zoloft (sertraline). You mentioned specifically the 'SleepGels', which contain diphenhydramine (the same antihistamine that is in Benadryl).

The good news here is that there is no specific interaction between Zoloft and Unisom SleepGels. Unisom does not affect the metabolism or clinical effects of Zoloft in any way.

However, and this is important to note, some common side effects of Zoloft include drowsiness and dizziness.

Since Unisom products are sedating, there is a risk of additive side effects when taken with Zoloft (e.g., additive sedative effects).

This generally isn't much of a concern since Unisom is intended for evening dosing to help sleep at night. Regardless, risk of additive sedation is important to be aware of.

Final Words

I hope you found this helpful!

Unisom and Zoloft can certainly be used together safely, just watch out for the potential of additive sedative effects, especially if Zoloft already makes you feel tired.

Reach back out anytime!


About the Pharmacist

Dr. Brian Staiger, PharmD

Dr. Brian has been practicing pharmacy for over 13 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical, program development, and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication-related questions! Dr. Brian Staiger also has herbalist training and educational certificates in the field of medical ethnobotany. Feel free to send him an email at Hello@HelloPharmacist.com! You can also connect with Dr. Brian Staiger on LinkedIn.

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