Medications and Drugs
Antidepressants
Pharmacy Author: Omudhome Ogbru, PharmD
Medical and Pharmacy Editor: Jay W. Marks, MD
What are antidepressants?
Antidepressants are the most prescribed therapy for
depression. The exact mechanism of action of antidepressants is unknown. The
prevailing theory is that antidepressants increase the concentration of one or
more brain chemicals
(neurotransmitters) that nerves in the brain use to communicate with one
another. The neurotransmitters affected by antidepressants are norepinephrine,
serotonin, and dopamine. The
different classes of antidepressants differ in the neurotransmitters they
affect. This determines some of their side effects and potential drug
interactions. All available antidepressants are effective, and for most cases of
depression there is no good evidence that any antidepressant
is more effective than another. Side effects and potential drug interactions are
major factors that influence selection of antidepressants and compliance with
therapy. This article discusses side effects and potential drug interactions of
the major antidepressant classes.
What are monoamine oxidase inhibitors (MAOIs)?
MAOIs were the first class of antidepressants to be
developed. They fell out of favor because of concerns about interactions with
certain foods and numerous drug interactions. MAOIs elevate the levels of
norepinephrine, serotonin, and dopamine by inhibiting an enzyme called monoamine
oxidase. Monoamine oxidase breaks down norepinephrine, serotonin, and dopamine.
When monoamine oxidase is inhibited, norepinephrine, serotonin, and dopamine are
not broken down, increasing the concentration of all three neurotransmitters in
the brain.
Monoamine oxidase also breaks down tyramine, a chemical present in
aged cheese, wines, and other aged foods. Since MAOIs inhibit monoamine oxidase
they decrease the break down of tyramine from ingested food, increasing the
level of tyramine in the body. Excessive tyramine can elevate blood pressure and cause a
hypertensive crisis. Patients treated with MAOIs should adhere to recommended
dietary modifications that reduce the intake of tyramine. Interestingly, the 6
mg/24 hour dose of selegiline transdermal system (EMSAM) does not require dietary restrictions because at this
dose EMSAM does not substantially inhibit tyramine. Higher selegiline
transdermal system (EMSAM) doses require
dietary restrictions.
MAOIs are associated with several significant drug
interactions; limiting their usefulness in patients who are treated with
multiple drugs. MAOIs interact with drugs that increase serotonin activity in
the brain, increase norepinephrine, constrict blood vessels, or inhibit
monoamine oxidase. Drugs that increase serotonin in the brain include:
- selective
serotonin reuptake inhibitors, for example,
fluoxetine (Prozac) and
sertraline
(Zoloft),
- serotonin norepinephrine reuptake inhibitors, for example,
venlafaxine
(Effexor) and desvenlafaxine (Pristiq),
- tricyclic antidepressants, for example,
imipramine (Tofranil),
- St. John's Wort,
- meperidine,
- tramadol (Ultram),
- methadone,
- propoxyphene (Darvon), and
- other MAOIs, for example, tranylcypromine (Parnate),
phenelzine (Nardil).
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
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