Can You Take Zoloft And Zofran Together?

Thanks for reaching out to us!

This is a situation where there is a documented interaction between the two drugs you state in your question (Zoloft and Zofran), but they can, and often are, used together. However, if they are used together, the individual taking both should be monitored for side effects and adverse reactions.

What Is The Interaction?

Both Zoloft (sertraline) and Zofran (ondansetron), although used for different conditions, affect the neurotransmitter serotonin.

Combining Zoloft and Zofran increases the risk of a rare, but serious condition known as serotonin syndrome. Symptoms of serotonin syndrome include:

• Altered mental status
• Shaking
• High blood pressure
• Sweating
• Convulsions
• Dilated pupils
• Increased heart rate

Certain individuals are more at risk for this interaction than others. This includes those who take multiple drugs that affect serotonin levels and those who take high doses of serotonergic drugs.

The prescribing information for Zofran warns about using it with other drugs that affect serotonin:

Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT3 receptor antagonists [like Zofran] and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs). Monitor for the emergence of serotonin syndrome. If symptoms occur, discontinue ZOFRAN and initiate supportive treatment 

As mentioned, serotonin syndrome is rare, but serious if it occurs and typically requires immediate medical attention.

More Detail On The Interaction

The interaction occurs between Zofran and Zoloft because they both affect serotonin, but in different ways.

For a simplified description, Zofran acts as a serotonin receptor antagonist (specifically, a 5HT3 antagonist). Blocking this receptor essentially increases levels of available serotonin in the brain, which then is able to stimulate other serotonin receptors.

Zoloft is an SSRI (selective serotonin reuptake inhibitor). As the drug class name (SSRI) suggests, Zoloft inhibits the reuptake of serotonin, increasing overall levels in the brain, which allows it to repeatedly stimulate receptors.

It is not known how often serotonin syndrome occurs or what the overall risk is, but it is thought the be relatively low.

As mentioned though, there are risk factors (e.g. taking multiple serotonergic drugs at high doses, for a long period of time) to be aware of. The prescribing information for Zofran specifically notes that the highest risk individuals may be those undergoing surgery who received Zofran prior to the end of anesthesia, as there have been several case reports filed that fit this situation.

What Is The Recommendation For Taking Both Drugs?

The overall risk of serotonin syndrome occurring with the combined use of Zofran and Zoloft is thought to be low, but it is hard to know definitively.

The ideal scenario is to avoid combining multiple serotonergic drugs, but if you and your doctor decide that Zofran and Zoloft represent your best therapy option, it is important to be aware of, and monitor for symptoms of serotonin syndrome, especially when first starting treatment, or with dose increases on either drug.

Most studies investigating the risk of serotonin syndrome with Zofran only report case studies (i.e. a detailed report of the symptoms, signs, diagnosis, treatment, and follow-up of an individual patient), which is typically regarded as the lowest level of evidence.

Large-scale studies reaching definitive conclusions have not been completed.

It is important to note that some studies are very dubious that Zofran really represents an increased risk of serotonin syndrome at all. One such study states:

[Zofran] and related compounds have been demonstrated not to possess these properties [cause large increases in serotonin] to a significant degree and are not reliably documented as causing ST [serotonin toxicity]. It is therefore highly doubtful that these drugs are capable of contributing to ST [serotonin toxicity], a conclusion that can be confidently predicted from their pharmacological actions

If you do take Zofran and Zoloft together, and you notice symptoms that could be serotonin syndrome, it is important to stop both medications and seek medical attention.

Final Words

I want to reiterate that it is not uncommon to see Zofran used with other serotonergic drugs, especially since Zofran is generally used only on an 'as needed basis', and most likely won't be taken on a consistent basis with Zoloft. It is just important to be aware of the risk, and to be aware of serotonin syndrome symptoms.

I do want to say as well that nausea associated with SSRIs like Zoloft tends to be worse when it is first started, and then gets better over time, typically after a few weeks. There are other anti-nausea medications that don't affect serotonin that may help get you through this period.

It would be extremely uncommon for a provider to prescribe Zofran to be taken with every dose of Zoloft. If anything, it may be prescribed to someone to help only if necessary, for a short period of time, and certainly not with every dose.

Additionally, there may be some anti-anxiety medications that don't affect serotonin that could be an option for you. Be sure to talk to your doctor about your concerns.