What Should You Not Mix Buspar With? A Guide to Interactions

October 13, 2025 •

4 min read

An estimated 2.7% of U.S. adults have had generalized anxiety disorder in the past year, a condition often treated with medications like Buspar (buspirone) [1.9.1]. To ensure safety and effectiveness, it is critical to know what you should not mix Buspar with, as interactions can be serious.

Quick Summary

Buspar (buspirone) can interact negatively with various substances. Key interactions to avoid include MAOIs, which can cause dangerously high blood pressure, and other serotonergic drugs, which increase the risk of serotonin syndrome. Alcohol and grapefruit juice also pose significant risks.

Key Points

MAOI Interaction is Critical: Never mix Buspar with Monoamine Oxidase Inhibitors (MAOIs) or take them within 14 days of each other to avoid dangerously high blood pressure and serotonin syndrome [1.2.2, 1.4.3].
Avoid Alcohol: Combining alcohol with Buspar significantly increases drowsiness, dizziness, and cognitive impairment, and should be avoided [1.6.1, 1.6.3].
No Grapefruit Juice: Consuming large amounts of grapefruit or its juice can dramatically increase Buspar levels in the body, leading to more side effects [1.5.1, 1.5.2].
Risk of Serotonin Syndrome: Be cautious when combining Buspar with other serotonergic drugs like SSRIs, SNRIs, and triptans, as this increases the risk of serotonin syndrome [1.3.1, 1.7.2].
Check All Medications: Always inform your doctor about all medications, including over-the-counter drugs and herbal supplements like St. John's Wort, as they can alter Buspar's effectiveness and safety [1.3.1, 1.8.1].
Enzyme Interactions: Certain drugs (CYP3A4 inhibitors/inducers) can either raise buspirone to toxic levels or lower it to ineffective levels, requiring dose adjustments [1.8.1].
Consult Professionals: Always consult your doctor or pharmacist before starting, stopping, or changing the dosage of any medicine while taking Buspar [1.2.1].

Understanding Buspar (Buspirone)

Buspar, the brand name for the generic drug buspirone, is a prescription medication primarily used to treat generalized anxiety disorder (GAD) [1.6.2]. It belongs to a class of drugs known as anxiolytics and works by affecting neurotransmitters in the brain, specifically serotonin and dopamine receptors, to help regulate mood and alleviate anxiety symptoms like fear, tension, and irritability [1.3.5, 1.6.2]. Unlike benzodiazepines, another class of anti-anxiety medication, buspirone is not a central nervous system (CNS) depressant and is considered to have a lower potential for abuse and dependence [1.6.2, 1.6.6]. However, its effectiveness and safety are highly dependent on avoiding certain drug and food interactions.

The Most Dangerous Interaction: MAOIs

The most severe and dangerous interaction with buspirone involves a class of antidepressants called Monoamine Oxidase Inhibitors (MAOIs) [1.2.1, 1.3.3]. Combining buspirone with an MAOI, or taking it within 14 days of stopping an MAOI, is contraindicated [1.2.2, 1.4.3, 1.4.6]. This combination can lead to two life-threatening conditions:

Dangerously High Blood Pressure (Hypertensive Crisis): The interaction can cause a rapid and severe increase in blood pressure [1.4.1, 1.4.5].
Serotonin Syndrome: Both buspirone and MAOIs increase serotonin levels. When taken together, serotonin can accumulate to toxic levels, causing symptoms like agitation, confusion, rapid heart rate, muscle rigidity, and seizures [1.4.2, 1.4.4, 1.7.4].

Examples of MAOIs include isocarboxazid, phenelzine, selegiline, and tranylcypromine, as well as the antibiotic linezolid and methylene blue [1.2.2, 1.4.4].

Other Serotonergic Drugs and Serotonin Syndrome

Beyond MAOIs, mixing buspirone with other drugs that increase serotonin can also elevate the risk of serotonin syndrome [1.3.3]. While the risk may be lower than with MAOIs, caution is essential [1.4.2]. Symptoms of serotonin syndrome range from mild (shivering, diarrhea) to severe (high fever, seizures, unconsciousness) [1.7.4].

Drugs that can contribute to this risk include:

SSRIs (Selective Serotonin Reuptake Inhibitors): e.g., sertraline (Zoloft), escitalopram (Lexapro) [1.3.1, 1.8.1].
SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors): e.g., duloxetine (Cymbalta), venlafaxine (Effexor) [1.3.1, 1.8.1].
Tricyclic Antidepressants (TCAs): e.g., amitriptyline [1.3.1].
Triptan Migraine Medications: e.g., sumatriptan [1.3.1, 1.8.5].
Herbal Supplements: St. John's wort can increase the risk of serotonin syndrome and may also speed up the breakdown of buspirone, making it less effective [1.8.1].

Medications That Affect Buspirone Levels

Buspirone is broken down (metabolized) in the body by an enzyme called CYP3A4 [1.4.5, 1.8.3]. Some substances can inhibit or induce this enzyme, leading to dangerously high or ineffectively low levels of buspirone in the bloodstream.

CYP3A4 Inhibitors (Increase Buspirone Levels and Side Effects): These drugs slow the breakdown of buspirone, increasing its concentration and the risk of side effects like dizziness, drowsiness, and nausea [1.3.1, 1.8.1].

Certain Antibiotics: Erythromycin [1.3.1, 1.4.5].
Antifungals: Itraconazole, ketoconazole [1.4.5, 1.8.1].
Calcium Channel Blockers: Diltiazem, verapamil [1.3.1, 1.8.2].
Antidepressants: Nefazodone [1.3.1].
HIV Medications: Ritonavir (found in Paxlovid) [1.3.1].

CYP3A4 Inducers (Decrease Buspirone Levels and Effectiveness): These drugs speed up the breakdown of buspirone, which can make the medication less effective at treating anxiety [1.8.1].

Anticonvulsants: Carbamazepine, phenobarbital [1.8.1].
Antibiotics: Rifampin [1.4.5, 1.8.1].

Food and Substance Interactions

Grapefruit Juice Drinking grapefruit juice, especially in large amounts, can significantly increase the levels of buspirone in your body [1.5.2, 1.5.6]. Like CYP3A4 inhibitors, grapefruit blocks the enzyme that metabolizes the drug, leading to higher concentrations and a greater risk of side effects such as drowsiness and dizziness [1.5.1, 1.5.3]. It's recommended to avoid large quantities of grapefruit or grapefruit juice while taking buspirone [1.3.2, 1.6.5].

Alcohol It is strongly advised to avoid drinking alcohol while taking buspirone [1.3.2, 1.6.3]. Both alcohol and buspirone can cause drowsiness, dizziness, and impaired judgment [1.6.4, 1.6.6]. Mixing them can amplify these sedative effects, making it dangerous to drive or operate machinery [1.3.3]. Alcohol can also interfere with the liver's ability to metabolize the medication, potentially increasing its side effects and undermining its therapeutic benefits for anxiety [1.3.3, 1.6.2].

Buspar Interaction Summary Table


Substance/Drug Class	Type of Interaction	Potential Risk(s)
MAOIs (e.g., phenelzine)	Severe / Contraindicated	Dangerously high blood pressure, Serotonin Syndrome [1.2.1, 1.4.1]
Alcohol	Severe	Increased sedation, dizziness, impaired coordination, reduced medication effectiveness [1.3.3, 1.6.1]
Grapefruit Juice	Major	Increases buspirone levels in the body, raising the risk of side effects [1.5.1, 1.5.2]
Other Antidepressants (SSRIs, SNRIs)	Serious	Increased risk of Serotonin Syndrome [1.3.1, 1.8.2]
CYP3A4 Inhibitors (e.g., erythromycin, ketoconazole)	Serious	Increased buspirone levels and side effects [1.4.5, 1.8.1]
CYP3A4 Inducers (e.g., rifampin, carbamazepine)	Moderate	Decreased buspirone levels and effectiveness [1.8.1]
St. John's Wort	Moderate	May decrease buspirone effectiveness and increase risk of Serotonin Syndrome [1.8.1]

Conclusion

To ensure the safe and effective use of Buspar (buspirone), it is crucial to be aware of what you should not mix it with. The most critical interactions to avoid are with MAOIs, alcohol, and grapefruit juice due to the risks of hypertensive crisis, enhanced sedation, and serotonin syndrome. Always inform your healthcare provider and pharmacist about all prescription medications, over-the-counter drugs, and herbal supplements you are taking to prevent potentially harmful interactions [1.3.1]. Consistent communication with your doctor is the best way to manage your treatment and mitigate risks.

For more information from an authoritative source, you can visit the DailyMed page for Buspirone Hydrochloride. [1.4.5]

Frequently Asked Questions

The most dangerous drugs to mix with Buspar are Monoamine Oxidase Inhibitors (MAOIs). This combination is contraindicated and can cause a life-threatening increase in blood pressure or serotonin syndrome. You should not take Buspar within 14 days of using an MAOI [1.2.2, 1.4.1].

No, it is recommended to avoid drinking alcohol while taking Buspar. The combination can increase side effects like dizziness, drowsiness, and impaired coordination, making activities like driving unsafe [1.3.3, 1.6.1].

Grapefruit and grapefruit juice inhibit the enzyme (CYP3A4) that breaks down Buspar in your body. This can lead to significantly higher levels of the medication, increasing your risk of side effects like dizziness and drowsiness [1.5.1, 1.5.6].

Taking Buspar with SSRI antidepressants like Zoloft (sertraline) or Lexapro (escitalopram) can increase the risk of a rare but serious condition called serotonin syndrome. While they are sometimes prescribed together, it requires careful monitoring by a doctor for symptoms like agitation, confusion, or rapid heart rate [1.3.1, 1.4.2].

Signs of a serious interaction, particularly serotonin syndrome, include agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, heavy sweating, and tremors [1.7.4]. If you experience these symptoms, seek medical attention immediately.

You should consult your doctor or pharmacist before taking any over-the-counter medications. Some antihistamines or other CNS depressants found in cold medicines can enhance the sedative effects of Buspar, increasing drowsiness and impairment [1.3.3].

Mixing Buspar with the herbal supplement St. John's Wort is not recommended. It can increase your risk of developing serotonin syndrome and may also speed up the breakdown of Buspar, making your prescribed dose less effective for treating anxiety [1.8.1].