Buspirone (sold under the brand name BuSpar) is not an MAOI. It belongs to a completely different drug class called anxiolytics, and it works through a distinct mechanism in the brain. However, buspirone and MAOIs have a dangerous interaction, which is likely why this question comes up so often.
How Buspirone Actually Works
Buspirone is classified as an anxiolytic, meaning it’s specifically designed to treat anxiety. It primarily works by acting on serotonin receptors in the brain. Rather than broadly changing neurotransmitter levels the way many psychiatric medications do, buspirone targets specific receptor sites that help regulate mood and anxiety.
MAOIs, by contrast, work by blocking an enzyme called monoamine oxidase. This enzyme normally breaks down three key brain chemicals: serotonin, norepinephrine, and dopamine. By disabling that cleanup process, MAOIs allow all three chemicals to build up, which can relieve depression. Common MAOIs include phenelzine, tranylcypromine, isocarboxazid, and selegiline.
The two drug types differ in almost every practical way. Buspirone is prescribed for generalized anxiety disorder. MAOIs are primarily prescribed for depression, typically after other antidepressants have failed. Their side effect profiles, dietary restrictions, and drug interaction lists look nothing alike.
Why Buspirone and MAOIs Can’t Be Combined
Even though buspirone isn’t an MAOI, the two should never be taken together. The FDA labeling for buspirone states clearly that giving it to someone already on an MAOI “may pose a hazard,” and recommends against combining them. The primary risk is dangerously high blood pressure, which can escalate quickly and become a medical emergency.
There is also a theoretical risk of serotonin syndrome, a condition caused by too much serotonin activity in the brain. Because buspirone acts on serotonin receptors and MAOIs prevent serotonin from being broken down, combining them could push serotonin levels past a safe threshold. That said, buspirone on its own is considered less likely to cause severe serotonin toxicity compared with other drug combinations. The greater concern with MAOIs is that serotonin syndrome episodes involving them tend to be more severe and more likely to lead to serious outcomes, including death.
The 14-Day Washout Period
If you’re switching between buspirone and an MAOI in either direction, a minimum 14-day gap is recommended between stopping one and starting the other. This waiting period, called a washout, gives the first medication enough time to fully clear your system so the two drugs don’t overlap in your body.
This 14-day rule applies whether you’re coming off an MAOI and starting buspirone, or stopping buspirone and beginning an MAOI. MAOIs are unusual in that their effects linger long after the last dose because the enzyme they block needs time to regenerate. Skipping or shortening this window puts you at risk for the same blood pressure spike and serotonin problems that would occur if you took both drugs simultaneously.
Other Medications That Interact With Buspirone
The MAOI interaction is the most prominent warning on buspirone’s label, but it isn’t the only drug interaction to be aware of. Buspirone can also interact with other serotonin-affecting medications, certain antifungal drugs, and some antibiotics that influence how quickly your liver processes the medication. Grapefruit juice can raise buspirone levels in your blood as well, because it slows down the same liver pathway.
If you’re currently taking an MAOI or have taken one in the past two weeks, that’s essential information to share before starting buspirone. The same applies in reverse: let your prescriber know you’re on buspirone before starting any new medication, especially one that affects serotonin or blood pressure.