Abilify is not an MAOI. Abilify (aripiprazole) is an atypical antipsychotic, sometimes called a third-generation antipsychotic. It works through a completely different mechanism than monoamine oxidase inhibitors and belongs to a separate drug class entirely.
How Abilify Actually Works
Abilify is a partial agonist at dopamine receptors, which means it fine-tunes dopamine activity rather than simply blocking or boosting it. When dopamine levels are too high, it dials them down. When they’re too low, it nudges them up. It also interacts with certain serotonin receptors, helping stabilize both neurotransmitter systems in areas of the brain involved in mood, motivation, and thinking.
This is what makes Abilify “atypical” compared to older antipsychotics that only block dopamine. Its unique pharmacological profile is why it’s used for a range of conditions, including schizophrenia, acute manic episodes in bipolar disorder, and as an add-on treatment for major depressive disorder when an antidepressant alone isn’t enough.
How MAOIs Work Differently
MAOIs, or monoamine oxidase inhibitors, are a class of antidepressant that works by blocking the enzyme responsible for breaking down neurotransmitters like serotonin, dopamine, and norepinephrine. By disabling that cleanup enzyme, MAOIs let these brain chemicals build up to higher levels. The FDA-approved MAOIs include phenelzine, tranylcypromine, isocarboxazid, and selegiline.
The key distinction: Abilify acts directly on neurotransmitter receptors, adjusting how brain cells respond to chemical signals. MAOIs act on an enzyme, preventing the brain from recycling its chemical messengers. These are fundamentally different approaches to changing brain chemistry.
Why the Difference Matters Day to Day
One of the most practical differences is diet. People taking classic MAOIs must follow a tyramine-restricted diet, avoiding aged cheeses, cured meats, fermented foods, and certain other items. Tyramine is a compound normally broken down by the same enzyme that MAOIs block. When that enzyme is inhibited, tyramine can accumulate and cause dangerous spikes in blood pressure. Abilify carries no such dietary restriction because it doesn’t interfere with the monoamine oxidase enzyme at all.
MAOIs also come with a long list of drug interactions, particularly with other medications that raise serotonin levels. The combination can trigger serotonin syndrome, a potentially serious condition involving agitation, rapid heart rate, and high body temperature. Abilify has its own set of potential side effects and interactions, but they stem from its activity at dopamine and serotonin receptors rather than enzyme inhibition.
Can Abilify Be Used Alongside an MAOI?
This combination is uncommon but not unheard of. Published case reports describe clinicians adding Abilify to an MAOI regimen for patients with treatment-resistant depression, particularly when psychotic features are involved. However, the medical literature on combining atypical antipsychotics with MAOIs is extremely limited, and some clinicians are cautious about it due to uncertainty around the risk of serotonin syndrome or other adverse outcomes. If you’re taking an MAOI and wondering whether Abilify could be part of your treatment plan, that’s a conversation to have with your prescriber, who can weigh the risks for your specific situation.
Why People Confuse the Two
The confusion likely comes from the fact that both Abilify and MAOIs affect the same neurotransmitters, specifically dopamine and serotonin. And because Abilify is sometimes prescribed alongside antidepressants for depression, people may assume it falls into an antidepressant category like MAOIs. But affecting the same chemicals doesn’t make two drugs the same class. Abilify adjusts how receptors respond to dopamine and serotonin. MAOIs prevent those chemicals from being broken down. The destination overlaps, but the route is entirely different.