Grapefruit and its juice have been shown to interact with a number of medications, including some antidepressants. This interaction can potentially lead to elevated drug levels in the body and an increased risk of side effects and toxicity. While rare, some grapefruit-medication combinations can potentially be fatal if consumed in large quantities over an extended period of time. However, occasional or moderate intake of grapefruit with most antidepressants is unlikely to cause serious harm.
What causes the grapefruit interaction?
Grapefruit contains a compound called furanocoumarin that inhibits certain liver enzymes involved in the metabolism (breakdown) of many medications. When these enzymes are disabled, more of the drug remains in the body at higher concentrations instead of being metabolized and eliminated.
The liver enzymes most affected by grapefruit are: CYP3A4 and CYP1A2. These enzymes metabolize approximately 50% of all medications. As a result, about 50% of all drugs may have potential interactions with grapefruit.
Which antidepressants are affected?
Many antidepressants, particularly older tricyclic antidepressants and newer serotonin reuptake inhibitors, interact with grapefruit because they are metabolized by the CYP3A4 liver enzyme. The highest risk combinations include:
- Amitriptyline (Elavil)
- Clomipramine (Anafranil)
- Duloxetine (Cymbalta)
- Fluoxetine (Prozac)
- Sertraline (Zoloft)
However, more research is needed to fully establish the effects of grapefruit on many antidepressants. Consult with a health care provider or pharmacist about your specific medication.
What are the effects of the interaction?
Consuming grapefruit or grapefruit juice while taking certain antidepressants can lead to higher levels of the drug in your system. Adverse health effects may include:
- Increased risk of overdose toxicities – rapid heartbeat, tremors, agitation, confusion, seizures
- Serotonin syndrome – high fever, rapid heart rate, shivering, sweating, dilated pupils, muscle rigidity
- Gastrointestinal symptoms – nausea, vomiting, diarrhea
- Abnormal bleeding
- Rapid mood swings or fluctuations
The severity of these symptoms depends on the specific antidepressant, the amount of grapefruit consumed, and how long grapefruit has been part of the diet while on the medication.
Is the interaction potentially fatal?
There are a few reports of fatal outcomes linked to grapefruit consumption with certain medications. However, these cases often involve very large amounts of grapefruit juice consumed daily over many days or weeks.
For most people eating a normal amount of grapefruit occasionally, fatal outcomes would be extremely rare with antidepressants. However, it’s still essential to avoid consistent large servings of grapefruit if you’re on medications with known interactions.
Are there any exceptions?
A few newer antidepressants are less likely to interact with grapefruit, including:
- Bupropion (Wellbutrin)
- Mirtazapine (Remeron)
- Vilazodone (Viibryd)
- Vortioxetine (Trintellix)
However, it’s still a good idea to be cautious and consult your doctor or pharmacist when adding grapefruit to your diet while on any antidepressant.
Who is most at risk?
Those at highest risk for grapefruit medication interactions include:
- People over age 50. Liver enzymes that break down medications decline with age.
- Kidney disease or kidney transplant patients. Impaired kidney function makes it harder to clear medications from the body.
- Patients taking multiple medications. Moredrug competition for metabolism can increase the effects of grapefruit interactions.
However, anyone taking an antidepressant has some level of risk if also consuming grapefruit or its juice on a regular basis.
How much grapefruit is dangerous?
The amount of grapefruit that could potentially cause interactions varies widely based on the medication, the individual, and other factors. Some general guidelines include:
- Even a small 200mL glass of grapefruit juice may be enough to cause excessive drug levels of some antidepressants if consumed regularly.
- Eating only grapefruit segments could potentially trigger interactions for some antidepressants, especially if eaten daily.
- The risk is highest with drinking large amounts of grapefruit juice (more than 1 liter daily) over consecutive days.
Consult your doctor for specific dosage recommendations with your antidepressant. As a precaution, it may be best to limit yourself to no more than one grapefruit or 200mL of juice every 2-3 days at most if on a potentially interacting medication.
Should grapefruit be avoided completely with antidepressants?
Most experts recommend avoiding grapefruit altogether if you are taking a medication highly sensitive to interactions, such as certain antidepressants. However, if you wish to consume grapefruit occasionally, a few precautions can help minimize risks:
- Limit yourself to no more than 1/2 grapefruit or small glass of juice every 2-3 days.
- Take your antidepressant and grapefruit at least 4 hours apart. Separating the timing helps reduce effects on liver enzymes.
- Ask your doctor to monitor your medication blood levels for the first month of adding grapefruit to ensure no significant changes.
If you do experience any unusual side effects, muscle twitches, abdominal pain, or heart flutters after eating grapefruit, discontinue use and contact your healthcare provider.
Are white grapefruits safer?
Many medications interact with grapefruit due to the furanocoumarin compound. However, some evidence suggests white grapefruit varieties have lower levels of furanocoumarin compared to red/pink grapefruits.
Initial research indicates white grapefruit may be less likely to cause grapefruit drug interactions. However, more studies are needed to establish if white grapefruit can be safely consumed with antidepressants. Play it safe by treating white grapefruit similarly to other varieties when taking antidepressants.
Can grapefruit be eaten after stopping the antidepressant?
Yes, it is generally safe to consume grapefruit products once you are no longer taking a potentially interacting antidepressant under doctor’s supervision. However, keep the following in mind:
- It can take 1-2 weeks for an antidepressant to be fully eliminated from your body after stopping the medication.
- Liver enzymes need time to recover after being inhibited by the antidepressant for potentially years.
- Ask your doctor how long they recommend waiting until starting to eat grapefruit again just to be safe.
It’s best to slowly reintroduce grapefruit back into your diet after stopping an antidepressant, rather than consuming large amounts right away.
Should I avoid other citrus fruits?
Grapefruit has the most significant effects, but other citrus fruits have potential to interact with medications too. However, the compounds involved and the degree of interactions varies.
Some experts recommend erring cautiously and limiting the entire citrus family if you are on a medication sensitive to grapefruit. Speak with your healthcare provider about consumption of the following citrus fruits:
- Oranges
- Tangerines
- Lemons
- Limes
- Pomelos
While not technically citrus fruits, some other produce contains similar compounds, including mangoes, apples, lichi, and pomegranates. Discuss a diet plan with your doctor to ensure safety while taking your antidepressant.
Are grapefruit seeds and peel safe?
The furanocoumarins and other compounds that trigger grapefruit medication interactions are most concentrated in the juice and pulp. Grapefruit seeds likely have minimal effects.
The peels also have lower concentrations of furanocoumarins compared to the juice. However, compounds in the outer and inner peels may still potentially inhibit liver enzymes. Play it safe by avoiding use of zest, essence, or extract when taking antidepressant medications affected by grapefruit.
Can grapefruit interfere with other psychiatric drugs?
Yes, grapefruit can also potentially interact with other psychiatric medications that are metabolized by the CYP3A4 liver enzyme, including:
- Buspirone (BuSpar – anxiety)
- Zolpidem (Ambien – insomnia)
- Aripiprazole (Abilify – schizophrenia)
- Haloperidol (Haldol – schizophrenia)
- Risperidone (Risperdal – bipolar disorder)
Avoid eating grapefruit and drinking its juice when taking these and other sensitive psychiatric medications except under medical guidance. The interactions could potentially cause adverse effects.
Should I take extra precautions with grapefruit juice or extract supplements?
Yes, extra precautions are recommended if using concentrated grapefruit juice or extract supplements, including:
- Avoid taking antidepressants within 4-6 hours of consuming grapefruit supplements.
- Read labels carefully for ingredients and furanocoumarin concentrations.
- Start with low doses of supplements and monitor for side effects.
- Consult your doctor before taking supplements if you’re on interacting medications.
Commonly sold in capsule form, these supplements can contain high amounts of furanocoumarins that may significantly inhibit liver enzyme metabolism of antidepressants if adequate precautions aren’t taken.
Conclusion
Grapefruit contains compounds that can increase blood levels of certain antidepressants by inhibiting liver metabolism. This interaction can potentially lead to increased side effects and risks if high amounts of grapefruit are consumed regularly.
While fatal overdoses are very rare, it’s recommended to avoid or limit grapefruit intake when on a medication with known interactions. Speak to your doctor or pharmacist for dosage advice and alternatives to grapefruit with your specific antidepressant medication.
