Hypertensive crisis People 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 develop a
hypertensive crisis, which can be fatal. Examples of
foods and beverages with potentially high levels of tyramine include cheese,
Chianti wine, and pickled fish. Excessive concentrations of tyramine in blood plasma can lead to hypertensive crisis by increasing the release of
norepinephrine (NE), which causes blood vessels to constrict by activating
alpha-1 adrenergic receptors. Ordinarily, MAO-A would destroy the excess NE; when MAO-A is inhibited, however, NE levels get too high, leading to dangerous increases in blood pressure. RIMAs are displaced from MAO-A in the presence of
tyramine, rather than inhibiting its breakdown in the liver as general MAOIs do. Additionally,
MAO-B remains free and continues to metabolize tyramine in the stomach, although this is less significant than the liver action. Thus, RIMAs are unlikely to elicit tyramine-mediated hypertensive crisis; moreover, dietary modifications are not usually necessary 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).
Drug interactions The most significant risk associated with the use of MAOIs is the potential for
drug interactions with over-the-counter, prescription, or illegally obtained medications, and some
dietary supplements (e.g.,
St. John's wort or
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 [epinephrine] dosage should be reduced by 75%, and duration is extended). MAOIs should not be combined with other psychoactive substances (antidepressants, painkillers, stimulants, including prescribed, OTC and illegally acquired drugs, etc.) except under expert care. Certain combinations can cause lethal reactions; common examples include
SSRIs,
tricyclics,
MDMA,
meperidine,
tramadol, and
dextromethorphan, whereas combinations with certain
psychedelics like
LSD or
psilocybin appear to be relatively safe. On the other hand, MAOIs can strongly potentiate psychedelics metabolized by MAO like
dimethyltryptamine (DMT),
5-MeO-DMT, and
2C-B, potentially resulting in serious
toxicity or death. While safer than general MAOIs, still possess significant and potentially serious drug interactions with many common drugs; in particular, they can cause
serotonin syndrome or hypertensive crisis when combined with almost any
antidepressant or
stimulant, common migraine medications, certain herbs, or most cold medicines (including
decongestants,
antihistamines, and
cough syrup). Ocular
alpha-2 agonists such as
brimonidine and
apraclonidine are glaucoma medications which reduce intraocular pressure by decreasing aqueous production. These alpha-2 agonists should not be given with oral MAOIs due to the risk of hypertensive crisis.
Withdrawal Antidepressants including MAOIs have some
dependence-producing effects, the most notable one being a
discontinuation syndrome, which may be severe especially if MAOIs are discontinued abruptly or too rapidly. The dependence-producing potential of MAOIs or antidepressants in general is not as significant as
benzodiazepines. Discontinuation symptoms can be managed by
tapering, a gradual reduction in dosage over a period of days, weeks or sometimes months to minimize or prevent withdrawal symptoms. MAOIs, as with most antidepressant medication, may not alter the course of the disorder in a significant, permanent way, so it is possible that discontinuation can return the patient to the pre-treatment state. This consideration complicates prescribing between an MAOI and an SSRI, because it is necessary to clear the system completely of one drug before starting another. One physician organization recommends the dose to be tapered down over a minimum of four weeks, followed by a two-week washout period. The result is that 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. == Mechanism of action ==