Selegiline is a nonselective MAOI, inhibiting not only the monoamine oxidase B (MAO-B) enzyme in the central nervous system but also monoamine oxidase A (MAO-A) elsewhere in the body. In the digestive tract, MAO-A normally metabolizes tyramine, a dietary amine that is found in high concentrations in foods such as aged cheese and red wine. The breakdown of tyramine in the gut prevents significant amounts of it from being absorbed and circulated throughout the body. Tyramine is a potent pressor-leading to constriction of blood vessels-which ultimately results in increased blood pressure. Large amounts of tyramine can lead to hypertensive crises, resulting in stroke, heart attack, and even death. Because the medication is absorbed from the skin patch and bypasses the gut wall, it is thought that transdermal selegiline will have a significantly reduced effect on MAO-A in the digestive tract. In addition, at lower doses, selegiline is thought to inhibit MAO-B preferentially, while at higher doses both A and B isoenzymes are affected. With significantly reduced inhibition of digestive tract MAO-A, dietary restrictions are not considered necessary for the lower dose. In considering starting this drug, consult with a pharmacist about multiple classes of drug-drug interactions. This drug has not been evaluated in people with cancer.
Foods that contain large amounts of tyramine, such as cheese, chicken liver, chocolate, beer, and wine, may provoke hypertension (initially manifesting as headache) and cardiac dysrhythmias.
St. John's wort
There continue to be high levels of enthusiasm for the use of herbs and dietary supplements for controlling symptoms and improving health-related quality of life and well-being. One popular herbal agent that has been used to treat depression is St. John's wort, a plant with Greek origins. The major active constituents in St. John's wort are hypothesized to be melatonin, hypericin, hyperforin, and adhyperforin, although hypericin may not reach sufficient concentrations in humans to have biologic activity. Hypericin is thought to be a monoamine oxidase inhibitor, while hyperforin and adhyperforin are believed to inhibit the reuptake of serotonin, dopamine, and norepinephrine.[48,49,50,51] These mechanisms of action provide the rationale for evaluating St. John's wort for depression management.
During the last 25 years, many trials have compared St. John's wort to placebo, to antidepressants, and sometimes to both placebo and antidepressants. A wide range of results have emerged, from finding no differences between arms, to finding St. John's wort improving outcomes over placebo for moderate depression, to finding St. John's wort preferable to placebo in general, to finding St. John's wort equal to antidepressants in alleviating depressive symptoms.;[53,54][Level of evidence: I] Older studies comparing St. John's wort to antidepressant therapy tended to use low doses of antidepressants and did not titrate up by response to the usual doses used for managing depression. The best overview of the research in this area is provided in a meta-analysis of randomized controlled trials. Conclusions from this meta-analysis, which includes 37 trials, are that St. John's wort does not have a clinically important effect on major depressive disorder and that for milder depression, it may have some effect (but it is not large).