Depression is associated with reduced levels of serotonin, dopamine, and noradrenaline in the brain. Major antidepressant classes act to increase levels of these neurotransmitters, including: Selective serotonin reuptake inhibitors (SSRIs) Serotonin–noradrenaline reuptake inhibitors (SNRIs) Tricyclic antidepressants (TCAs) Monoamine oxidase inhibitors (MAOIs) This article focuses on MAOIs, describing their mechanism of action, cautions and contraindications, side effects, and clinically significant interactions. Mechanism of action Monoamine oxidase (MAO) is an enzyme that breaks down several key neurotransmitters, including serotonin, dopamine, and noradrenaline. MAOIs inhibit this enzyme, leading to increased concentrations of these neurotransmitters within synaptic clefts, thereby improving mood and reducing symptoms of depression. There are two types of monoamine oxidase, A and B. Serotonin and noradrenaline are metabolised by MAO-A Dopamine and tyramine are metabolised by MAO-A and -B. Type Examples Irreversible MAO-A & B inhibitors Isocarboxazid, Phenelzine, Tranylcypromine Reversible MAO-A inhibitor Moclobemide Other drugs with MAO activity Linezolid MAOIs are now used infrequently because of their potentially dangerous food and drug interactions Adobe stock Fig 1: Mechanism of action of antidepressants. Close-up of neurons and synaptic cleft with neurotransmitters, Receptor, Mitochondria and MAO enzyme. Cautions and contraindications Cautions Contraindications Epilepsy Diabetes Postural hypotension Withdrawal syndrome* Delay in onset of effect* Serotonin syndrome* Phaeochromocytoma Cerebrovascular disease Congestive heart failure Recent use of TCAs, carbamazepine, buspirone, SSRIs, SNRIs or other MAOIs *(see Depression article for further information) Side effects Category Common Effects Cardiovascular Postural hypotension, hypertensive responses (especially with tyramine-containing food) Gastrointestinal Nausea, constipation, dry mouth Neurological Dizziness, insomnia, headache Interactions Interaction with other antidepressants Do not start another antidepressant within 2 weeks of stopping an MAOI (or 3 weeks if starting clomipramine or imipramine This prevents serotonin syndrome, a potentially life-threatening condition caused by excess serotonergic activity If switching to an MAOI, an appropriate washout period must be observed based on the previous antidepressant’s half-life. Interaction with tyramine rich foods MAO normally breaks down tyramine, a compound found in many aged or fermented foods. MAO inhibition allows tyramine to accumulate, causing displacement of noradrenaline, adrenaline, and dopamine from pre-synaptic storage vesicles and consequently release of these neurotransmitters results in severe hypertension (hypertensive crisis) Moclobemide, being reversible and selective for MAO-A, is less likely to cause this reaction. Created in BioRender. Boucher, M. (2025) https://BioRender.com/j5ydas6 Fig 1: tyramine rich foods to avoid whilst taking MAOI drugs References Onset of action of antidepressants | The BMJ Antidepressant drugs | Treatment summaries | BNF | NICE Nardil 15 mg film-coated tablets – Summary of Product Characteristics (SmPC) – (emc) Sub Laban T, Saadabadi A. Monoamine Oxidase Inhibitors (MAOI) [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539848/ Do you think you’re ready? Take the quiz below Pro Feature - Quiz Monoamine Oxidase Inhibitors (MAOIs) Question 1 of 3 Submitting... Skip Next Rate question: You scored 0% Skipped: 0/3 More Questions Available Upgrade to TeachMePharmacy Pro Challenge yourself with over 2100 multiple-choice questions to reinforce learning Learn More Rate This Article