Does doxycycline interact with Zoloft? (3 side effects)

In this article, we will discuss whether doxycycline interacts with Zoloft – a selective serotonin reuptake inhibitor (SSRI). We will also discuss some research studies and how one can ensure the safe and effective use of these medications together. 

Does doxycycline interact with Zoloft?

No, doxycycline does not necessarily interact with Zoloft. However, these medications may cause some additive side effects when used together. Zoloft (sertraline) is one of the most commonly prescribed antidepressants (1). 

It’s common for people to experience seasonal infections while being treated with an antidepressant and may require an antibiotic to manage the symptoms. Doxycycline does not pharmacologically interact with Zoloft or affect the metabolism of this medication (2). 

So, you can take these two together but only if prescribed by your healthcare provider. This is because both Zoloft and doxycycline are prescription medications and should not be taken unless prescribed by a qualified healthcare provider.

What are the potential risks of taking doxycycline with Zoloft?

The potential risks of taking doxycycline with Zoloft are: (3,4)

Gastrointestinal (GI) side effects:

GI side effects are linked to both doxycycline and Zoloft and taking these medications together may cause more pronounced side effects. Doxycycline, being an antibiotic, targets bacterial growth. 

It not only affects bad bacteria but also diminishes the growth of good gut bacteria, which can have many physiological benefits. This can trigger GI side effects. Zoloft, on the other hand, is known for GI side effects, which may be more prominent during the early course of your treatment. 

So, taking the two together might increase the intensity of these side effects, which may include:

  • Nausea
  • Vomiting
  • Diarrhoea 
  • Abdominal pain
  • Acid reflux
  • Indigestion 
  • Bloating 

Headaches and back pain

These side effects may be caused by a combination of doxycycline and Zoloft and have been reported in hospital settings. However, these side effects are more commonly associated with higher doses and long-term use of these medications.

Additional side effects

In addition to headaches and back pain, the combination of doxycycline and Zoloft may also lead to:

  • Dizziness
  • Fatigue
  • Mouth sores
  • Palpitations 

What does research suggest?

There is limited research on the potential interaction between Zoloft and doxycycline, and such cases have not been frequently reported. However, people are different and can respond differently to medications. 

One case study was presented with toxic hepatitis after the administration of doxycycline, sertraline, and two other medications (5). Although this complication might not be directly linked to the use of Zoloft and doxycycline together, the combination can add stress to the liver, exacerbating any pre-existing hepatic symptoms.

How to ensure the safe use of doxycycline with Zoloft?

The following points are important for the safe use of doxycycline:

  • Take both doxycycline and Zoloft exactly as your doctor prescribed. Stick to the prescribed doses and follow the recommended timing.
  • Do not try to take extra doses.
  • Avoid alcohol while you’re on these medications. It can affect both your depression and the infection in your body.
  • Let your doctor know about all the medications you’re taking, including over-the-counter ones. Some drugs don’t work well together.
  • If you have other health conditions, tell your doctor. 
  • Keep an eye out for anything unusual. If you notice new symptoms or side effects, inform your provider.

What to do if taking doxycycline with Zoloft causes side effects?

If you’re taking doxycycline with sertraline and start feeling unusual, please reach out to your provider. Both of these medications can cause disturbing GI side effects in some people, so they should be paired cautiously if you’re someone who is generally susceptible to GI issues, like people with an ulcer. 

When taken for a long time, these medications can cause several other side effects, which might be too concerning for some people. However, antibiotics are usually taken for a short span of time, as opposed to Zoloft, which is taken for months. 

So, it’s best to let your doctor know about the side effects you are experiencing. This helps your provider determine whether the current choice of medication is right for you or if your treatment plan or doses need to be changed.

The safety of taking Zoloft with antibiotics

In my experience as a pharmacist, I have come across many patients who took sertraline with antibiotics. Some people might experience GI side effects, for which I always recommend taking probiotics and maintaining a good diet. 

When you take probiotics and opt for gastro-protective foods, these side effects do get better, if not go away completely. However, individuals are different and have different underlying factors affecting their health. 

It is also important to note that not all antibiotics can be taken with Zoloft – such as clarithromycin can increase the risk of serotonin syndrome if taken with sertraline. So, it’s important to stick to your doctor’s recommended antibiotic and not take these medications more often than recommended.


  1. Singh HK, Saadabadi A. Sertraline. 2023 Feb 13. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 31613469. Available from:
  1. Patel RS, Parmar M. Doxycycline Hyclate. 2023 May 22. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 32310348. 
  1. National Library of Medicine. Sertraline: MedlinePlus Drug Information [Internet]. Bethesda (MD): U.S. National Library of Medicine. Available from:
  1. National Library of Medicine. Doxycycline: MedlinePlus Drug Information [Internet]. Bethesda (MD): U.S. National Library of Medicine. Available from: 
  1. García-Aparicio J, Herrero-Herrero JI. Hepatitis tóxica tras tratamiento secuencial con cotrimoxazol, levofloxacino, doxiciclina y sertralina en paciente con infección respiratoria [Toxic hepatitis following sequential treatment with cotrimoxazol, levofloxacin, doxycycline and sertraline in a patient with a respiratory infection]. Farm Hosp. 2010 May-Jun;34(3):152-4. Spanish. doi: 10.1016/j.farma.2009.10.005. Epub 2010 Jan 12. PMID: 20471573. 

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