Hypertensive crisis & tyramine
Patients taking MAOIs generally need to change their diets to limit or avoid foods and beverages containing tyramine. If large amounts of tyramine are consumed, they may suffer hypertensive crisis, which can be fatal.[3] Examples of foods and beverages with potentially high levels of tyramine include liver and fermented substances, such as alcoholic beverages and aged cheeses.[25] (See a List of foods containing tyramine).
Tyramine leads to hypertensive crisis by increasing the release of norepinephrine (NE), which causes blood vessels to constrict (through binding to alpha-1 adrenergic receptors).[26] Ordinarily, MAO-A would destroy the excess NE. When MAO-A is inhibited, though, NE levels get too high, leading to dangerous increases in blood pressure.
Of note, no dietary modifications are needed when taking a reversible inhibitor of MAO-A (i.e., moclobemide) or low doses of selective MAO-B inhibitors (e.g., selegiline 6 mg/24 hours transdermal patch).[26][27][28]
Drug interactions
The most significant risk associated with the use of MAOIs is the potential for interactions with over-the-counter and prescription medicines, illicit drugs or medications, and some dietary supplements (e.g., St. John's wort, tryptophan). It is vital that a doctor supervise such combinations to avoid adverse reactions. For this reason, many users carry an MAOI-card, which lets emergency medical personnel know what drugs to avoid. (E.g., adrenaline dosage should be reduced by 75%, and duration is extended.)[25]
Tryptophan supplements should not be consumed with MAOIs as the potentially fatal serotonin syndrome may result.[29]
MAOIs should not be combined with other psychoactive substances (antidepressants, painkillers, stimulants, both legal and illegal etc.) except under expert care. Certain combinations can cause lethal reactions, common examples including SSRIs, tricyclics, MDMA, meperidine,[30] tramadol, and dextromethorphan.[31] Agents with actions on epinephrine, norepinephrine, or dopamine must be administered at much lower doses due to potentiation and prolonged effect.
Nicotine, the substance most implicated in tobacco addiction, has been shown to have "relatively weak" addictive properties when administered alone.[32] The addictive potential increases dramatically after co-administration of an MAOI, which specifically causes sensitization of the locomotor response in rats, a measure of addictive potential.[33][34] This may be reflected in the difficulty of smoking cessation, as tobacco contains naturally-occurring MAOI compounds in addition to the nicotine.[35][36][37]
Withdrawal
Antidepressants including MAOIs have some dependence-producing effects, the most notable one being a withdrawal syndrome, which may be severe especially if MAOIs are discontinued abruptly or overly rapidly. However, the dependence-producing potential of MAOIs or antidepressants in general is not as significant as benzodiazepines. Withdrawal symptoms can be managed by a gradual reduction in dosage over a period of weeks, months or years to minimize or prevent withdrawal symptoms.[38]
MAOIs, as with any antidepressant medications, do not alter the course of the disorder, so it is possible that discontinuation can return the patient to the pre-treatment state.[39]
This consideration greatly complicates switching a patient between a MAOI and a SSRI, because it is necessary to clear the system completely of one drug before starting another. If one also tapers dosage gradually, the result is that for weeks a depressed patient will have to bear the depression without chemical help during the drug-free interval. This may be preferable to risking the effects of an interaction between the two drugs, but it is often not easy for the patient.[citation needed]
Listing of interactions
The MAOIs are infamous for their numerous drug interactions, including the following kinds of substances:
Substances that are metabolized by monoamine oxidase, as they can be boosted by up to several-fold.
Substances that increase serotonin, norepinephrine, or dopamine activity, as too much of any of these neurochemicals can result in severe acute consequences, including serotonin syndrome, hypertensive crisis, and psychosis, respectively.
Such substances that can react with MAOIs include:
Phenethylamines: 2C-B, mescaline, phenethylamine (PEA), etc.
Amphetamines: amphetamine,[40] MDMA, dextroamphetamine, methamphetamine, DOM, etc.
Tryptamines: DMT, psilocin/psilocybin ("Magic Mushrooms"), etc.
Lysergamides: ergolines/LSA, LSD ("Acid"), etc.
Norepinephrine, and/or dopamine reuptake inhibitors:
Serotonin-norepinephrine reuptake inhibitors (SNRIs): desvenlafaxine, duloxetine, milnacipran, venlafaxine.
Norepinephrine-dopamine reuptake inhibitors (NDRIs): amineptine, bupropion, methylphenidate, nomifensine.
Norepinephrine reuptake inhibitors (NRIs): atomoxetine, mazindol, reboxetine.
Tricyclic antidepressants (TCAs): amitriptyline, butriptyline, clomipramine, desipramine, dosulepin, doxepin, imipramine, lofepramine, nortriptyline, protriptyline, trimipramine.
Tetracyclic antidepressants (TeCAs): amoxapine, maprotiline.
Phenylpiperidine derivative opioids: meperidine/pethidine, tramadol, methadone, fentanyl, dextropropoxyphene, propoxyphene.
Others: brompheniramine, chlorpheniramine, cocaine, cyclobenzaprine, dextromethorphan (DXM), ketamine, MDPV, nefazodone, phencyclidine (PCP), pheniramine, sibutramine, trazodone
Serotonin, norepinephrine, and/or dopamine releasers: 4-methylaminorex (4-MAR), amphetamine, benzphetamine, cathine, cathinone, diethylcathinone, ephedrine, levmetamfetamine, lisdexamfetamine, MDMA ("Ecstasy"), methamphetamine, pemoline, phendimetrazine, phenethylamine (PEA), phentermine, propylhexedrine, pseudoephedrine, phenylephrine, tyramine.
Local and general anesthetic in surgery and dentistry in particular those containing epinephrine. There is no universally taught or accepted practice regarding dentistry and use of MAOIs such as phenelzine and it is, therefore, vital to inform all clinicians especially dentists of the potential effect of MAOIs and local anesthesia. In preparation for dental work, withdrawal from phenelzine is specifically advised, however since this takes two weeks it is not always a desirable or practical option. Dentists using local anesthesia are advised to use a non-epinephrine anesthetic such as mepivacaine at a level of 3%. Specific attention should be paid to blood pressure during the procedure and the level of the anesthetic should be regularly and appropriately topped up since non-epinephrine anestetics take longer to come into effect and wear off faster. Patients taking phenelzine are advised to notify their psychiatrist prior to any dental treatment.
Certain other supplements: Hypericum perforatum ("St John's wort"), inositol, Rhodiola rosea, S-adenosyl-L-methionine (SAMe), L-theanine.
Antibiotics such as Linezolid[41]
Other monoamine oxidase inhibitors.
