Grapefruit Interactions With Bipolar Drugs

Sliced grapefruit and glass of grapefruit juice on wood
Westend61 / Getty Images
Table of Contents
View All
Table of Contents

What is the most important information I should know about grapefruit interactions?

Grapefruit and grapefruit juice can affect how some bipolar medications are metabolized. Always talk to your doctor about your medications and any potential food/drug interactions you should be aware of.

Grapefruit can interfere with the metabolism of certain drugs, including bipolar medications. As a result, eating grapefruit or drinking grapefruit juice when taking these medications can inadvertently increase their concentration to potentially toxic levels.

Bipolar drugs are not the only ones affected. Also on the no-fly list are medications used to treat everything from high cholesterol and arrhythmia to allergies and HIV. Even Viagra can be impacted by grapefruit consumption.

Impact of Grapefruit Juice

A number of psychotropic drugs, including those used treat anxiety, depression, and psychosis, are among the agents grapefruit juice may interact with.

This is because grapefruit contains furanocoumarins, an organic compound that blocks an enzyme that normally breaks down certain medications. While other citrus fruits like pomelos, limes, and Seville oranges also contain furanocoumarins, they haven't been studied as closely.

When this enzyme is blocked, the drug concentration levels in the blood will be higher than expected. In some cases, the intended effect and/or side effects of the drug will be stronger—even dangerous.

Degrees and Persistence of Effect

The degree to which grapefruit can affect certain drugs can vary. For some medications, one small glass of juice can result in what would be equivalent to a double or triple dose.

For example, as much as 99% of BuSpar (buspirone) is normally metabolized before the drug enters the bloodstream. When taken with grapefruit juice, the concentration can increase by 400%. Or, as demonstrated in research, four-fold.

At the same time, the effects of grapefruit can be long-lasting, interacting with certain drugs anywhere from several hours to a few days after ingestion.

Any drug that will interact with grapefruit will have all of these defining elements:

  • It will be taken orally;
  • It will have very low to intermediate absolute bioavailability; and
  • It will be metabolized by the cytochrome P450 3A4 enzyme (CYP3A4).

Grapefruit and some of the related citrus can irreversibly inhibit that enzyme. Such drugs should not be eaten with grapefruit or any of the related citrus, or alternative medications should be prescribed.

Although it is probably purely speculative to suggest who the most vulnerable patient would likely be, people over 45 years old are the prime purchasers of grapefruit and receive the most prescriptions for drugs.

List of Affected Medications

All told, over a dozen drugs commonly used to treat symptoms of bipolar disorder that are known to be affected, in differing degrees, by grapefruit.

  • Anafranil (clomipramine)
  • BuSpar (buspirone)
  • Elavil (amitriptyline)
  • Halcion (triazolam)
  • Luvox (fluvoxamine)
  • Prozac (fluoxetine)
  • Seroquel (quetiapine)
  • Serzone (nefazodone)
  • Tegretol (carbamazepine)
  • Trazodone (desyrel)
  • Valium (diazepam)
  • Versed (midazolam)
  • Zoloft (sertraline)

Lamictal (lamotrigine) is one bipolar medication that does not appear to interact with grapefruit juice.

While clinically significant events due to grapefruit/drug interactions have been reported with some medications, more research is needed to better understand the severity and risk associated with such interactions.

Before You Mix Grapefruit With Medications

Always read the packet insert to understand which interactions can occur. Typically, you can find this in or around the fifth paragraph, where it would read: "Talk with your doctor before including grapefruit or grapefruit juice in your diet while you are taking this medicine." 

Each year, more drugs are identified as having a possible interaction with grapefruit. However, you may still be able to enjoy grapefruit or grapefruit juice if taken according to your doctor's instructions. Alternatively, you may be able to substitute other citrus fruits or drinks to obtain health benefits.

Speak with your doctor and be sure to tell them about any medications, substances, or supplements you are currently taking.

3 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Bailey DG, Dresser G, Arnold JM. Grapefruit-medication interactions: forbidden fruit or avoidable consequences?. CMAJ. 2013;185(4):309–316. doi:10.1503/cmaj.120951

  2. Lilja JJ, Kivistö KT, Backman JT, Lamberg TS, Neuvonen PJ. Grapefruit juice substantially increases plasma concentrations of buspirone. Clinical Pharmacology and Therapeutics. 1998;64(6):655-660. doi:10.1016/S0009-9236(98)90056-X

  3. Greenblatt DJ, Derendorf H. Grapefruit-medication interactionsCMAJ. 2013;185(6):507. doi:10.1503/cmaj.113-2109

By Marcia Purse
Marcia Purse is a mental health writer and bipolar disorder advocate who brings strong research skills and personal experiences to her writing.