Grapefruit Interactions With Bipolar Drugs

Sliced grapefruit and glass of grapefruit juice on wood
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Grapefruit juice may seem like the ideal drink for a good, old-fashioned American breakfast, but when it comes to washing down your bipolar medications, think again. Unlike some types of citrus fruit, grapefruit can interfere with the metabolization of certain drugs, inadvertently increasing 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 is complicated by the otherwise healthy effects of grapefruit.

Impact

A number of psychotropic drugs, including those used treat anxiety, depression, and psychosis, are among the 80 agents grapefruit juice is known to interfere with. Forty-three of those drugs had serious adverse effects.

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 by 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 as much as 400%. Or, as demonstrated in this 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. Alternately, you can avoid grapefruit altogether and substitute with (non-Seville) orange juice. 

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 also 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, there are 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)

Always read the packet insert in its entirety 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." 

A Word From Verywell

Each year, an increasing number of drugs are identified as having a possible interaction with grapefruit. In the end, you can usually still enjoy the grapefruit if taken wisely and enjoy the benefits of its combination of vitamin C, fiber, potassium, lycopene, and choline. Speak with your doctor if in doubt.

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  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

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