Antidepressant Drugs

Antidepressants are among the most frequently prescribed agents in medicine. They are a highly effective, relatively safe, and nonaddictive class of therapeutic agents. Antidepressants do not elevate mood in nondepressed people and have no abuse potential. Their primary use is in the treatment of major depressive disorder, although many antidepressants have other established uses such as in the treatment of anxiety and eating disorders.

Our understanding of antidepressants mechanism of action relates to the monoamine hypothesis of depression. This hypothesis suggests that depression follows a dysfunction of one or more of the monoamine neurotransmitters including norepinephrine (NE), serotonin (5-HT), and dopamine (DA). It follows, therefore, that antidepressants work by increasing monoamine-mediated neurotransmission in one or more ways. The three most established hypotheses for mechanism of antidepressant action are (1) reuptake inhibition (i.e., block the reuptake of NE, 5-HT, DA, or all three, into nerve terminals thereby increasing the amount of the monoamine in the synapse); (2) interaction with the 5-HT, NE, or DA receptors to mimic the effects of these natural monoamines; and (3) block inhibition (i.e., block the [Page 81]metabolic degradation of NE, 5-HT, or DA at the nerve terminals to increase the amount in the synapse).

Antidepressants are not general mood elevators and selectively alleviate symptoms of depression, including extreme sadness, loss of interest, decreased energy, inability to concentrate, sleep disturbance, and appetite changes. Because all antidepressants essentially target the same underlying substrate (monoamine neurotransmitters), no antidepressant is superior to others in the treatment of major depressive disorder. Selection of an antidepressant, therefore, depends on a patient's unique symptoms and the different medication side effect and drug interaction profiles.

In general, treatment with antidepressant medications requires 3 to 6 weeks of continuous therapy at therapeutic doses before symptoms of depression improve. Moreover, not every patient given an antidepressant will have improvement in all symptoms and some patients will be resistant to treatment and will not respond to one or more medications. Antidepressant use in children, adolescents, and young adults is currently under scrutiny due to a possible increased risk of suicide in these age groups.