Cold Medications To Avoid While Taking Zoloft

In our latest question and answer, the pharmacist discusses which cold medications you can take and which you should avoid while taking the antidepressant Zoloft (sertraline).​

3 min read Updated Jun 2026 Read by 47,552 people
Cold Medications To Avoid While Taking Zoloft
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Jen asked

I take 25mg of Zoloft (sertraline) and have come down with a cold. Is it safe to take an over-the-counter cold/flu nighttime syrup? I’m a female in my mid 30’s and have been on this med for about 4 months.

Aug 31, 2022
The quick answer
  • Avoid NSAIDs like ibuprofen and naproxen while taking Zoloft because they can increase the risk of stomach bleeding, especially when combined with this medication. Dextromethorphan, a common cough suppressant, should be avoided with Zoloft due to the rare but serious risk of serotonin syndrome. Safe alternatives for cold symptoms include acetaminophen for pain and fever, antihistamines for congestion and runny nose, and guaifenesin to help clear mucus.
A quick summary of Dr. Brian Staiger, PharmD's full answer below, condensed by AI from that answer only (not from any outside source). The pharmacist's answer is the source of record.

Thanks so much for reaching out to us! Zoloft (sertraline) is an antidepressant classified as an SSRI (selective serotonin reuptake inhibitor) and is one of the most commonly used drugs to treat depression and associated illnesses. Due to the widespread use of antidepressants, questions regarding drug interactions come up often.

Everyone gets sick from time to time, be it from the flu, the common cold, or a variety of other infections. Treating the symptoms of these illnesses can sometimes be difficult if you are on prescription medication such as Zoloft. It is important to always check for potential drug interactions before using a product over the counter.

In regard to Zoloft (sertraline), there are some over-the-counter medications that you either want to avoid or take caution with and use only based on the direction of your doctor:

Use Caution With Zoloft

NSAIDs (e.g. Ibuprofen, Naproxen, Aspirin)

The combined use of selective serotonin reuptake inhibitors like Zoloft and NSAIDs can increase the risk of an upper GI bleed. This is especially true if you have had a history of GI bleeds or ulcerations in the past.

NSAIDs are used in combination with many over-the-counter cold products so be sure to read product labels! This precaution also includes bismuth subsalicylate, one of the ingredients in Pepto-Bismol.

Dextromethorphan (Delsym)

Caution should be taken when using Zoloft and dextromethorphan together. Dextromethorphan can increase serotonin levels in the body and has the potential of causing serotonin syndrome when used with other medications that affect serotonin.

Serotonin syndrome is characterized by the rapid development of hyperthermia, high blood pressure, and mental status changes.​​​ Although rare, it is extremely serious. Sometimes the combination of dextromethorphan and SSRIs can be used but should only be considered after speaking with your physician.

Pseudoephedrine (Sudafed)

Sudafed products can be used on occasion but must be used cautiously if you have a history of arrhythmia (e.g. QT prolongation) or other heart issues as the combination of SSRI medication and Sudafed can exacerbate these conditions.

OTC Medications Generally Considered Safe

  • Antihistamines: Antihistamines (e.g. Claritin, Zyrtec) are generally considered OK and safe to use. They can help with a variety of cold symptoms such as a runny nose and itchy, watery eyes. They can also help on occasion with congestion and coughing due to post-nasal drip as they can have a slight drying effect.
  • Acetaminophen: Tylenol (acetaminophen) is in most cases a better option for a pain reliever/fever reducer than NSAID medications.
  • Guaifenesin: Mucinex (guaifenesin) is generally considered OK to use. It can help thin out excess mucus and relieve chest congestion.​​
  • Zinc/Vitamin C: Zoloft is compatible with other cold remedies such as Zinc lozenges and vitamin C.

Be Sure To Look At Product Labels

It is important to look at the active ingredient list for any product you are considering purchasing. There are a variety of combination products that contain multiple ingredients, so you need to be aware of all the included ingredients in these products. In addition, there are many 'brand name extension' products that can contain ingredients you may not be aware of.

A 'brand name extension product' uses a commonly recognized brand name but contains multiple ingredients for different indications. For example, 'Mucinex Fast Max' contains more than just Mucinex. It also contains dextromethorphan and phenylephrine.

Final Words

There are a variety of safe and effective options over the counter available to you for the treatment of cough/cold symptoms. Just be sure to pick the appropriate product for your situation and read the ingredients!

References & sources
  1. Clinically significant drug interactions with newer antidepressants — PubMed
  2. Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update — PubMed
  3. Dextromethorphan-induced serotonin syndrome — PubMed
  4. Sertraline Monograph — PubChem
Glossary — Terms in This Answer
SSRI
A type of antidepressant medication that works by increasing serotonin levels in the brain by preventing its reuptake.
NSAIDs
Over-the-counter pain relievers and anti-inflammatory drugs such as ibuprofen and naproxen.
GI bleed
Bleeding in the stomach or intestines that can be a serious side effect when certain medications are combined.
Dextromethorphan
A cough suppressant found in many over-the-counter cold medicines that can interact with serotonin-affecting medications.
Serotonin syndrome
A serious medical condition caused by dangerously high serotonin levels, characterized by fever, high blood pressure, and mental changes.
Arrhythmia
An irregular heartbeat that can be worsened by certain medication combinations.
Antihistamines
Medications that reduce allergy and cold symptoms by blocking the body's histamine response.
Guaifenesin
An expectorant medication that helps thin mucus and relieve chest congestion.
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Dr. Brian Staiger, PharmD
About the pharmacist

Dr. Brian Staiger, PharmD

Clinical Pharmacy

Doctor of Pharmacy, board certified clinical pharmacist (BCPS), American Herbalist Guild, Medication Therapy Management certified

Brian Staiger, PharmD, BCPS, is a licensed pharmacist with more than 13 years of experience across retail pharmacy, clinical pharmacy, medication safety, pharmacy program development, and healthcare administration. He is the founder of HelloPharmacist.com, where he helps patients...

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