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Grapefruit can cause negative effects when mixed with certain antidepressants, such as sertraline (Zoloft)

CLAIM
Eating grapefruit while using antidepressants can cause overdose, other complications
DETAILS
Accurate: Grapefruit can cause drug toxicity when mixed with certain drugs, such as the antidepressant sertraline (sold under the brand name Zoloft).
Lack of context: The claim that grapefruit should be avoided entirely overlooks the fact that there isn’t evidence that it causes toxicity when mixed with certain other commonly prescribed antidepressants, such as fluoxetine (Prozac).
KEY TAKE AWAY
Grapefruit can interfere with certain medications because it contains compounds called furanocoumarins, which inhibit the activity of enzymes in the liver, specifically CYP3A4. This enzyme is responsible for metabolizing many drugs, and when it’s inhibited, the amount of a drug in the bloodstream can increase to dangerous levels. This can lead to a higher risk of side effects or toxicity, making it important for people on certain medications to avoid grapefruit and its juice.

FULL CLAIM: “You CANNOT eat grapefruit if you're on antidepressants. It could cause an overdose, amongst other complications.”

REVIEW


A Facebook post from 13 January 2025 claimed that eating grapefruit while taking antidepressants “could cause an overdose, amongst other complications”. The post was shared more than 2,000 times.

As we will explain below, there is an element of truth to this claim. Grapefruit, when mixed with certain medications, can cause the level of the drug in the bloodstream to increase dangerously and in turn lead to drug overdose or toxicity.

Why does grapefruit interact with certain medications in a harmful way?

Grapefruit contains furanocoumarins, a compound found in certain types of citrus fruits. Other citrus fruits containing furanocoumarins include pomelos, Seville oranges, and limes.

Furanocoumarins inhibit the activity of cytochrome P450 3A4 (CYP3A4), an enzyme mainly present in the liver and the intestine. CYP3A4 is responsible for the metabolism of prescription drugs in the body[1]. Drug metabolism allows for these compounds to be more easily excreted from the body. The U.S. Food and Drug Administration (FDA) explains:

“Many drugs are broken down (metabolized) with the help of a vital enzyme called CYP3A4 in the small intestine. Grapefruit juice can block the action of intestinal CYP3A4, so instead of being metabolized, more of the drug enters the blood and stays in the body longer. The result: too much drug in your body.

The amount of the CYP3A4 enzyme in the intestine varies from person to person. Some people have a lot of this enzyme and others just a little. So grapefruit juice may affect people differently even when they take the same drug.”


Figure 1 – How drug overdose in the body can occur due to grapefruit and medication interaction. Source: FDA.

Harvard Health adds:

“When grapefruit juice blocks [CYP3A4], it’s easier for the medication to pass from your gut to your bloodstream. Blood levels will rise faster and higher than normal, and in some cases the abnormally high levels can be dangerous.”

The FDA and Harvard Health further shared that psychiatric medications may experience what is sometimes referred to as the “grapefruit effect” when they’re mixed with grapefruit. Among the medications they list include benzodiazepines such as diazepam (Valium) and clonazepam (Klonopin), other medications for insomnia and anxiety like buspirone (BuSpar) and zolpidem (Ambien), and the antidepressant sertraline (Zoloft).

Should people taking antidepressants avoid grapefruit juice?

Antidepressants are medications prescribed to treat depression and other mood disorders, and they come in several classes, each working in different ways. Among the most commonly prescribed are selective serotonin reuptake inhibitors (SSRIs), which increase the levels of the neurotransmitter serotonin in the brain to improve mood and reduce anxiety.

Health agencies including Poison Control in the U.S. and the National Health Service (NHS) in the U.K. noted that mixing grapefruit with the SSRI sertraline (often sold under the brand name Zoloft) may cause an increased risk of side effects, toxicity, or serotonin syndrome.

A few very small studies in humans also found that grapefruit inhibited the metabolism of sertraline and increased the amount of sertraline in the blood[2,3].

We conducted a search# on PubMed, a repository of published biomedical research hosted by the U.S. National Library of Medicine, to determine whether an association of toxicity exists between grapefruit and other commonly prescribed antidepressants, such as fluoxetine (Prozac), bupropion (Wellbutrin), citalopram (Celexa), and escitalopram (Lexapro). The FDA notes that medications like statins for high cholesterol or certain types of blood pressure medication may interact with grapefruit, but we found no evidence of this association with the antidepressants in our search.

Conclusion

The “grapefruit effect” affects the activity of the CYP3A4 enzyme in the liver, which inhibits the metabolism of certain drugs and can lead to elevated drug levels in the bloodstream. In the case of certain antidepressants, such as sertraline, this may lead to harmful outcomes like serotonin syndrome. To reduce these risks, health agencies recommend avoiding grapefruit when taking sertraline.

 

NOTES

# The following PubMed queries were used in our search:

(grapefruit[Title/Abstract]) AND (sertraline[Title/Abstract])

(grapefruit[Title/Abstract]) AND (fluoxetine[Title/Abstract])

(grapefruit[Title/Abstract]) AND (bupropion[Title/Abstract])

(grapefruit[Title/Abstract]) AND (citalopram[Title/Abstract])

(grapefruit[Title/Abstract]) AND (escitalopram[Title/Abstract])

 

REFERENCES

Published on: 27 Jan 2025 | Editor:

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