Abilify (aripiprazole) is not an MAOI. It belongs to a completely different drug class called atypical antipsychotics, and it works through an entirely different mechanism in the brain. The two medications affect neurotransmitters in distinct ways, treat overlapping but different conditions, and carry different side effect profiles.
What Abilify Actually Is
Abilify is an atypical (second-generation) antipsychotic. It’s FDA-approved to treat schizophrenia, bipolar disorder, major depressive disorder (as an add-on to another antidepressant), irritability associated with autism, and Tourette’s disorder. That’s a broad range of uses, which is partly why people sometimes confuse it with other psychiatric medication classes.
What makes Abilify unusual, even among antipsychotics, is how it interacts with dopamine. Most antipsychotics simply block dopamine receptors. Abilify is a partial agonist, meaning it can both activate and dampen dopamine signaling depending on what’s happening in the brain. When dopamine levels are too high (as in psychosis), it dials activity down. When they’re too low (as in depression), it provides a mild boost. It has a very strong attraction to dopamine D2 and D3 receptors and also acts as a partial agonist at certain serotonin receptors. Even a dose as low as 1 mg per day occupies about 50% of D2 receptors, and 10 mg reaches roughly 95% occupancy.
How MAOIs Work Differently
MAOIs, or monoamine oxidase inhibitors, are a class of antidepressants that work by blocking an enzyme called monoamine oxidase. This enzyme normally breaks down three key neurotransmitters: serotonin, norepinephrine, and dopamine. By stopping that breakdown, MAOIs allow these chemicals to build up in the brain, which can relieve depression.
The FDA-approved MAOIs include isocarboxazid (Marplan), phenelzine (Nardil), and tranylcypromine (Parnate), all taken by mouth. Selegiline (Emsam) is available as a skin patch. These drugs are typically reserved for depression that hasn’t responded to newer antidepressants, in part because they require strict dietary restrictions. Foods high in tyramine, like aged cheeses and cured meats, can cause dangerous blood pressure spikes when combined with MAOIs.
The Key Differences at a Glance
- Drug class: Abilify is an atypical antipsychotic. MAOIs are antidepressants.
- Mechanism: Abilify modulates dopamine and serotonin receptors directly. MAOIs block an enzyme that breaks down neurotransmitters.
- Primary uses: Abilify treats psychosis, bipolar disorder, and treatment-resistant depression (as an add-on). MAOIs treat depression, particularly cases that haven’t responded to other medications.
- Dietary restrictions: Abilify has none. MAOIs require avoiding tyramine-rich foods.
Can Abilify Be Taken With an MAOI?
This is where it gets interesting. Unlike many psychiatric medications, Abilify does not appear to be contraindicated with MAOIs. A review of second-generation antipsychotics used alongside MAOIs found multiple positive reports for most agents, including aripiprazole. The notable exception was ziprasidone (Geodon), which has properties similar to certain antidepressants and has been linked to serotonin syndrome when combined with MAOIs.
That said, combining any two psychiatric medications requires careful oversight. If you’re switching between an MAOI and another medication, the general rule is that the first drug needs to be fully cleared from your system before starting the second. For most medications with a half-life of 24 hours or less, that means a taper period of 7 to 14 days followed by a washout period of about five half-lives, at which point roughly 97% of the drug has been eliminated. The specifics depend on the drugs involved and your individual situation.
Why the Confusion Happens
People often search this question because both Abilify and MAOIs affect dopamine and serotonin, and both can be prescribed for depression. The overlap in conditions treated can make it seem like these drugs might be in the same family. They’re not. Abilify works at the receptor level, fine-tuning how brain cells respond to neurotransmitter signals. MAOIs work at the chemical level, preventing neurotransmitters from being recycled and broken down. These are fundamentally different approaches, with different risks and different benefits.