Can you take Zoloft and Zofran together?

Can you take Zoloft and Zofran together?

It is not generally recommended to take Zoloft and Zofran at the same time. Zoloft (Sertraline) is one of the most commonly prescribed antidepressants, and Zofran (Ondansetron) is an antiemetic medication. 

The concomitant use of these two can increase the risk of a rare, but dangerous condition called serotonin syndrome. 

The relationship between Zoloft, Zofran, and Serotonin Syndrome 

Zoloft particularly works to increase the amount of serotonin in your brain, which is an excitatory monoamine neurotransmitter responsible for modulating mood, cognition, reward, learning, memory, and various other psychological processes (1). 

Zofran, although it has an entirely different mechanism of action and is used for different reasons, can also enhance serotonergic activity in your brain (2). 

The concomitant use of these two can dangerously increase the amount of active serotonin in your brain, which can lead to disturbing symptoms associated with serotonin syndrome. Common symptoms are (3):

  • Excessive sweating 
  • Fever with chills
  • confusion
  • Restlessness and fatigue
  • Headache, which often feels like your head is pounding
  • Changes in blood pressure and/or temperature
  • Nausea
  • Vomiting
  • Diarrhoea
  • Bradycardia
  • Tremors
  • Muscle twitching and muscle pain
  • Shivering and goosebumps

Serotonin syndrome is a rare condition and it can be triggered by a lot of medications or a combination of medications if higher doses are consumed. Zoloft, for instance, can cause serotonin syndrome if you take too much of it. However, it’s rare and there could be other factors contributing to it. 

Pharmacist’s advice 

It’s best not to combine Zoloft and Zofran. If you’re concerned about nausea or vomiting caused by Zoloft as a side effect, don’t worry. This side effect is quite common during the early course of your treatment and it eventually starts to fade away as your body adjusts to the antidepressant. 

For symptomatic relief, you can try other antiemetics which don’t affect your serotonin levels, like Bonine (Meclizine). You can ask your local pharmacist to guide you according to the availability of safe OTC antiemetics to use with Zoloft.

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MedlinePlus. Sertraline: MedlinePlus drug information [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2022 Feb 15; cited 2022 Dec 20]. Available from:


MedlinePlus. Ondansetron: MedlinePlus drug information [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2022 Feb 15; cited 2022 Dec 20]. Available from:


Simon LV, Keenaghan M. Serotonin Syndrome. 2022 Jul 19. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 29493999. Available from:

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