No, Prozac (fluoxetine) is NOT a monoamine oxidase inhibitor (MAO inhibitor).
Prozac is a selective serotonin reuptake inhibitor (SSRI), which works through a completely different mechanism than MAO inhibitors. 1, 2, 3
Drug Classification
Fluoxetine belongs to the SSRI class of antidepressants, which work by blocking the reuptake of serotonin in the synaptic cleft, thereby increasing serotonin availability. This is fundamentally different from MAO inhibitors, which work by blocking the enzyme monoamine oxidase that breaks down neurotransmitters like serotonin, norepinephrine, and dopamine 4.
Critical Safety Concern: Contraindication with MAOIs
The FDA label explicitly states that Prozac is contraindicated with MAO inhibitors due to the risk of serious, sometimes fatal reactions including serotonin syndrome 3. The specific requirements are:
- At least 14 days must elapse between stopping an MAOI and starting Prozac
- At least 5 weeks must elapse after stopping Prozac before starting an MAOI (due to fluoxetine's long half-life) 3
This contraindication exists precisely because Prozac is NOT an MAOI—combining two different classes of serotonergic drugs creates dangerous additive effects 5.
Serotonin Syndrome Risk
Concomitant use of SSRIs (like Prozac) with MAOIs is contraindicated because of increased risk of serotonin syndrome, which can present with mental status changes, neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic instability, potentially leading to fatalities 5.
Research Context (Not Clinically Relevant)
While some in vitro research has shown that fluoxetine can inhibit MAO enzymes at very high concentrations (Ki values of 76.3 μM for MAO-A and 17-18 μM for MAO-B) 6, 7, 8, 9, these concentrations are far higher than therapeutic levels achieved in clinical practice. The modest MAO inhibition observed in some animal studies (12-23% reduction) 6 is not clinically significant and does not change fluoxetine's classification as an SSRI.
Bottom line: Prozac is an SSRI, not an MAOI, and must never be combined with actual MAO inhibitors.