Buspirone, an anti-anxiety medication, interacts with a surprisingly wide range of drugs, supplements, and foods. The most dangerous combination is with MAOIs, which can trigger a life-threatening spike in blood pressure. But several other common medications and even grapefruit juice can cause problems ranging from excessive sedation to serotonin syndrome.
MAOIs: The Most Dangerous Interaction
Buspirone should never be taken with monoamine oxidase inhibitors (MAOIs), a class of antidepressants that includes phenelzine, tranylcypromine, and isocarboxazid. The combination can cause a hypertensive crisis, a sudden and dangerous surge in blood pressure. If you’re switching from an MAOI to buspirone, a minimum 14-day washout period is required between stopping the MAOI and starting buspirone.
The antibiotic linezolid also acts as an MAOI, so the same precaution applies. If you’re prescribed linezolid for an infection while taking buspirone, your prescriber needs to know.
Serotonin-Raising Medications
Buspirone stimulates serotonin receptors, which means combining it with other drugs that raise serotonin levels can tip you into serotonin syndrome. This is a potentially serious condition that typically develops within hours of adding or increasing a serotonergic drug. About two-thirds of cases show symptoms within six hours, and 75% within 24 hours. Symptoms include agitation, confusion, fever, rapid heart rate, and involuntary muscle jerking.
Medications that raise serotonin risk when combined with buspirone include:
- SSRIs like fluoxetine (Prozac), sertraline (Zoloft), and escitalopram (Lexapro)
- SNRIs like venlafaxine (Effexor) and duloxetine (Cymbalta)
- Tricyclic antidepressants like amitriptyline and nortriptyline
- Triptans used for migraines, such as sumatriptan
- Certain pain medications, particularly tramadol and meperidine
- Dextromethorphan, the cough suppressant found in many over-the-counter cold medicines
That said, buspirone is sometimes prescribed alongside an SSRI or SNRI intentionally, under medical supervision, to augment anxiety treatment. The risk isn’t always a hard no, but it does require careful monitoring. The concern is when these combinations happen without your prescriber knowing about everything you’re taking.
Drugs That Increase Buspirone Levels
Buspirone is broken down in the liver by a specific enzyme system. Drugs that block this enzyme cause buspirone to build up in your bloodstream, intensifying both its effects and its side effects like dizziness, drowsiness, and nausea.
Common medications that slow buspirone’s breakdown include certain antifungals (ketoconazole, itraconazole), certain antibiotics (erythromycin, clarithromycin), and some HIV medications. When these drugs are used alongside buspirone, a lower dose of buspirone is typically needed to avoid problems. If you’ve already been stabilized on a buspirone dose and then start one of these medications, a dose adjustment is usually necessary.
Drugs That Make Buspirone Less Effective
The opposite problem can also occur. Some medications speed up buspirone’s breakdown so dramatically that it stops working for anxiety. Rifampin, an antibiotic used for tuberculosis, is the most notable example. It reduces buspirone concentrations so substantially that the drug’s anti-anxiety effect can essentially disappear.
Other drugs with a similar effect include the seizure medications phenytoin and carbamazepine. If you start any of these while on buspirone, your anxiety may return not because the buspirone failed but because your body is clearing it too quickly.
Grapefruit Juice
Grapefruit juice blocks the same liver enzyme that many of the drugs above affect. Drinking it while taking buspirone can raise buspirone levels in your blood, leading to stronger side effects. The simplest approach is to avoid grapefruit juice entirely while on buspirone, or at least keep your intake consistent and let your prescriber know about it.
Alcohol
The FDA label for buspirone notes that formal studies did not find buspirone worsened alcohol-related impairment in motor and mental performance. That result is unusual for an anti-anxiety medication. Still, the official guidance recommends avoiding alcohol while taking buspirone. Both substances affect the central nervous system, and individual responses vary. In practice, the combination is less risky than mixing alcohol with benzodiazepines, but caution is still warranted.
St. John’s Wort and Other Supplements
St. John’s wort, a popular herbal supplement for mood, is a double threat with buspirone. It raises serotonin levels through a mechanism similar to antidepressants, creating a risk of serotonin syndrome when combined with buspirone. A published case report in the Journal of Psychopharmacology documented serotonin syndrome from this exact combination. Because St. John’s wort is sold over the counter and often perceived as harmless, this interaction catches people off guard.
St. John’s wort also induces the liver enzyme that breaks down buspirone, which could reduce buspirone’s effectiveness at the same time it’s adding serotonin risk. It’s one of the few substances that creates problems through two separate mechanisms simultaneously.
Pregnancy and Breastfeeding
Data on buspirone during pregnancy is limited but somewhat reassuring. A pregnancy registry found no birth defects among 72 infants exposed to buspirone during pregnancy, though studies on pregnancy complications like preterm delivery have not been done.
Buspirone does pass into breast milk in small amounts. One report found no short-term issues in an 11-week-old baby whose mother was taking 10 mg per day. Another report described seizure-like activity in a 3-week-old infant, though the mother was on multiple medications and the authors considered buspirone an unlikely cause. The product label recommends avoiding buspirone during breastfeeding if possible, while acknowledging the benefits may outweigh the risks depending on the situation.
What to Tell Your Prescriber
The broadest takeaway is that buspirone interacts with a long list of prescription drugs, over-the-counter cold medications, herbal supplements, and even a common fruit juice. Before starting buspirone, make sure your prescriber has a complete picture of everything you take, including supplements and things you might not think of as “medicine.” And if you start any new medication while already on buspirone, the same applies in reverse.