The same goal, two opposing strategies.
Nearly all antidepressants increase the level of “mood messengers” in the brain — serotonin, noradrenaline, and sometimes dopamine. But they do so in two radically different ways. Most block the recycling of these messengers. MAOIs do something else entirely.
Two brakes, two families
That is the whole difference: one family acts on recycling, the other on breakdown.
Block recycling
SSRIs, SNRIs and tricyclics prevent messengers from being taken back up too quickly. As a result, they remain in the synapse longer and have more effect. These three classes share the same basic action — they differ only in the messengers they target and their selectivity.
Switch off breakdown
MAOIs do not affect recycling. They disable the enzyme that destroys the messengers. The neuron then builds up a larger reserve — of all three messengers at once, including dopamine. In the simplified comparison below, this dopaminergic component is what sets them apart.
The four classes, side by side
Choose a class to see its mechanism and profile. Notice how dopamine lights up only for MAOIs.
● increased · ○ little or none. In this simplified comparison, the dopamine column distinguishes MAOIs.
What this mechanism changes in practice
Three direct consequences follow from switching off the enzyme rather than blocking recycling.
The dopamine bonus
By also increasing dopamine through inhibition of its breakdown, MAOIs have a different profile from the three families compared here. This may contribute to the activating effect of tranylcypromine, without being enough on its own to predict clinical response.
See the medicine profiles →Why a diet is needed
The same enzyme guards the gut against dietary tyramine. Switching it off allows tyramine through: this is both the origin — and the limit — of the dietary restrictions.
The tyramine diet in practice →Two interaction mechanisms to know
Combining an MAOI with a powerful serotonin inhibitor or releaser can cause serotonin toxicity. Certain sympathomimetics can instead trigger a hypertensive surge. Other combinations must be checked medicine by medicine.
The real danger, disentangled →Going further: two enzymes and the question of reversibility
Monoamine oxidase exists in two forms. MAO-A mainly handles serotonin, noradrenaline and tyramine; MAO-B is more involved with dopamine. The antidepressant effect depends on inhibition of MAO-A.
The three classic MAOIs are non-selective (they block both forms) and, above all, irreversible: they permanently disable the enzyme, and the body takes about two weeks to make new enzyme. This explains the transition intervals between treatments, and why the diet must continue for two to three weeks after stopping.
For practical prescribing information — doses, transition intervals (washout) and management of adverse effects — see our summary of the prescribing guide, based on the open-access international guide.
This website provides general information and cannot replace advice from a physician or pharmacist. Do not make any treatment decision without a healthcare professional. MAOIs involve real precautions — dietary and, above all, drug-interaction precautions — which are detailed on the relevant pages.