Are Cough/Congestion Medications Safe To Take With Zoloft?
In our latest question and answer, our pharmacist discusses which cough and decongestant medications are safe to take with Zoloft.

Question
What kind of cough and congestion medicine can I take with Zoloft?

Answered by Dr. Brian Staiger, PharmD
Medical Content Reviewed By HelloPharmacist
Staff
Last updated Apr 23, 2025
Key points
- Zoloft (sertraline) should be used cautiously with dextromethorphan, a commonly used drug in many over-the-counter cough products.
- Zoloft is generally considered safe to use with decongestants, like Sudafed, but should be used cautiously in those with certain heart conditions.
- Mucinex (guaifenesin), an expectorant, is safe to take with Zoloft.
Answer
Hello and thanks for reaching out to us! This is a great question. It's always a good idea to look into potential drug interactions when combining over-the-counter (OTC) meds with your prescriptions.
As it concerns Zoloft (sertraline), there are a few drugs that are commonly used to treat cough and congestion that you need to use cautiously. Let's start first with OTC cough medications.
Cough Medication With Zoloft: Use Caution
There are several different OTC cough medications available, including cough drops (e.g. Halls, Sucrets, Fisherman's Friend, etc...), herbal/natural products (e.g. honey-containing liquids), and products like Delsym, Robitussin & Mucinex.
There is one drug you want to be on the lookout for if you are taking Zoloft, and that is dextromethorphan, a commonly used cough suppressant found in numerous products (e.g. Mucinex DM, Delsym, NyQuil Severe, etc...). Unless otherwise directed by your doctor, you generally want to avoid taking Zoloft and dextromethorphan together.
Zoloft, an SSRI (selective serotonin reuptake inhibitor) is thought to work at least partially by increasing serotonin levels in the brain. Dextromethorphan has been reported to also affect serotonin levels, and the use of both together increases the risk of a rare, but serious, condition known as serotonin syndrome.
Serotonin syndrome is characterized by the rapid development of hyperthermia, high blood pressure, and mental status changes. Although rare, it is serious and requires medical attention.
There is some controversy regarding just how dangerous the combination of dextromethorphan and SSRIs, like Zoloft, is, with some studies suggesting the risk is extremely small, and really only present when higher than recommended doses of dextromethorphan are used.
Nevertheless, there are numerous case reports linking serotonin syndrome with dextromethorphan use, so it's important to be aware of this interaction. Generally, if there are other options available to you to help with your cough, those would be recommended first. Cough drops and products containing honey are safe to use.
For some individuals, dextromethorphan may be the best clinical option to help with cough, and it certainly has been used in combination with Zoloft safely. You should just make your doctor aware before using both.
As a final note here, although not specifically a cough medication, Mucinex, which contains the expectorant guaifenesin, is safe to take with Zoloft.
Nasal Decongestants With Zoloft: Use Caution
Nasal decongestants, both nasal and oral, are generally safe to take with Zoloft.
Nasal decongestants include:
- Afrin (oxymetazoline)
- Neo-Synephrine (phenylephrine)
- Sudafed (pseudoephedrine)
- Sudafed PE (phenylephrine)
The only real concern with using nasal decongestants with Zoloft is if you have certain pre-existing heart conditions, like QT prolongation (a type of arrhythmia). Both drugs can increase your risk of arrhythmias and exacerbate related pre-existing conditions. Otherwise, most sources do not report any specific drug interaction between decongestants and Zoloft.
Final Words
Thanks again for reaching out to us! If you have any other questions about specific cough or decongestant medications, please let us know. We're more than happy to provide some guidance for you.
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Dr. Brian Staiger, PharmD
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