There are three basic molecules, known chemically as monoamines, which are thought to play a role in mood regulation: norepinephrine, serotonin and dopamine. Antidepressant medications are categorized by how they affect these chemicals. The following are the major antidepressants classes.
Monoamine Oxidase Inhibitors
The monoamine oxidase inhibitors (MAOIs) were some of the first antidepressant medications developed. The neurotransmitters responsible for mood, primarily norepinephrine and serotonin, are also known as monoamines. Monoamine oxidase is an enzyme which breaks these substances down. Monoamine oxidase inhibitors, as the name implies, inhibits this enzyme, thus allowing a greater supply of these chemicals to remain available.
Tricyclics, also known as heterocyclics, came into broad use in the 1950's. These antidepressant drugs inhibit the nerve cell's ability to reuptake serotonin and norepinephrine, thus allowing a greater amount of these two substances to be available for use by nerve cells.
Selective Serotonin Reuptake Inhibitors
SSRI stands for Selective Serotonin Reuptake Inhibitor. These medications work, as the name implies, by blocking the presynaptic serotonin transporter receptor. This drug differs from the tricyclics in that it's action is specific to serotonin only. It's effect on norepinephrine is indirect, through the fact that falling serotonin "permits" norepinephrine to fall so preserving serotonin preserves norepinephrine.
Five newer antidepressants which do not fit into the above categories are: buproprion (Wellbutrin), nefazodone (Serzone), trazodone (Desyrel), venlafaxine (Effexor), and mirtazapine (Remeron).
The mechanism of bupropion's antidepressant activity is poorly understood, but is thought to be mediated through noradrenergic or dopaminergic pathways or both.(1)
Nefazodone and it's precursor trazodone both inhibit neuronal reuptake of serotonin and, to a lesser extent, norepinepherine. They also blocks postsynaptic 5-HT2 receptors.
Venlafaxine is a compound that is structurally unrelated to other antidepressants.(2) Like the TCAs, venlafaxine inhibits the neuronal uptake of both serotonin and norepinepherine. Venlafaxine has dose-dependent, sequential effects on the uptake pumps for serotonin and then norepinephrine.. At 75 mg/day, venlafaxine is predominantly a serotonin reuptake inhibitor (SRI) like the SSRIs. At 375 mg/day, it produces comparable norepinephrine uptake inhibition to an NSRI such as desipramine.(3)
Mirtazapine's unique mechanism of action does not involve enzyme inhibition or blockade of neurotransmitter reuptake. Mirtazapine increases the release of norepinepherine from central noradrenergic neurons by blocking the presynaptic inhibitory alpha-2 autoreceptors. It spares the alpha-1 postsynaptic receptor and therefore results in net increase noradrenergic transmission.
- Ascher JA, Cole JO, Colin JN, et al: Bupropion: A review of its mechanism of antidepressant activity. J Clin Psychiatry. 1995; 56(9):395-401.
- Holiday SM, Benfield P. Venlafaxine. A review of its pharmacology and therapeutic potential in depression. Drugs. 1995; 49(2): 280-294.
- Preskorn, S: Outpatient Management of Depression: A Guide for the Primary-Care Practitioner. PCI, 1999. Chap. 8.5.