Monoamine Oxidase Inhibitors in Depression Treatment

Monoamine oxidase inhibitors (MAOIs) represent a foundational class of antidepressants that exert their therapeutic effect by blocking the activity of the mitochondrial enzymes monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). By inhibiting these enzymes, MAOIs increase the synaptic availability of key neurotransmitters—serotonin, noradrenaline and dopamine—thereby alleviating symptoms of major depressive disorder. Initially introduced in the 1950s, non-selective, irreversible inhibitors such as phenelzine, tranylcypromine and isocarboxazid demonstrated robust efficacy but were constrained by dietary restrictions and potential drug–drug interactions leading to hypertensive crises. The advent of reversible and selective MAO-A inhibitors has mitigated some safety concerns, enabling more flexible dietary management and improved tolerability. In recent years, alongside a resurgence of interest in precision psychiatry, MAOIs have been re-evaluated for treatment-resistant depression, with emphasis on evidence-based protocols for initiation, monitoring of blood pressure, and safe switching strategies. Preclinical advances have further elucidated the role of MAO-B inhibition in dopaminergic modulation and synaptic plasticity, suggesting new pathways for optimising antidepressant response and expanding therapeutic indications beyond classical use.

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Monoamine Oxidase Inhibitors in Depression Treatment publication trend

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Technical terms

Monoamine oxidase (MAO): Mitochondrial enzyme responsible for the breakdown of monoamine neurotransmitters.

MAO-A and MAO-B: Isoforms of MAO with differing substrate selectivity; MAO-A primarily deaminates serotonin and noradrenaline, MAO-B preferentially deaminates phenylethylamine.

Tyramine syndrome: Hypertensive crisis triggered by ingestion of dietary tyramine when MAO activity is inhibited.

Treatment-resistant depression: Major depressive disorder that fails to remit after two or more adequate antidepressant trials.

Synaptic plasticity: The ability of synapses to strengthen or weaken over time in response to neuronal activity, underpinning learning and adaptive responses.

References

1. The prescriber’s guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression. CNS Spectrums (2022).
2. Selegiline ameliorates depression-like behaviors in rodents and modulates hippocampal dopaminergic transmission and synaptic plasticity. Behavioural Brain Research (2018).
3. Evolution of ideas about the risk of tyramine syndrome developing during therapy with irreversible non-selective monoamine oxidase inhibitors (to the 70th anniversary of the first use of this group of antidepressants). Неврология, нейропсихиатрия, психосоматика (2022).