Differences in Mechanism of Action Between Current and Future Antidepressants

Antidepressants are divided into several classes on the basis of their pharmacologic mechanisms of action, which are thought to be responsible for both their therapeutic actions and their side effect profiles. All classes currently available in the United States affect serotonin, norepinephrine, and/or dopamine neurotransmission. New agents in development also affect neurotransmission of such monoamines and include serotonin-norepinephrine reuptake inhibitors, serotonin-selective agents, selective monoamine oxidase inhibitors, and selective norepinephrine reuptake inhibitors. Treatments with entirely new mechanisms of action are also being studied, including hormone-linked treatments such as estrogen replacement therapy and the steroid antagonist mifepristone (RU-486 or C-1073); novel antagonist peptides such as corticotropin-releasing factor, neurokinins, and injectable pentapeptides; and agents that affect glutamate neurotransmission. The introduction of antidepressants with novel mechanisms of action could potentially revolutionize the treatment of depression.