How Antidepressant Medications Work: An Introduction
To understand how medications reduce the symptoms of depression, it is important to understand how the parts of our brain that govern mood work.
The brain cells (neurons) communicate with each other using chemicals called neurotransmitters, which they manufacture and release into the space between brain cells. The junction through which a neurotransmitter travels is the synapse, and it includes part of the membranes of the communicating neurons and the minuscule space between adjacent neurons. Once the neurotransmitters are released, they can either:
- be broken down by enzymes
- be sucked back into neurons (reuptake)
- reach another neuron across the synapse and connect there on a neurotransmitter receptor molecule
Once the neurotransmitter binds to the receptor molecule, the shape of the receptor site in three-dimensional space changes. This, in turn, can set off a very complex series of possible changes within the neuron cell membrane or inside the cell proper, immediately adjacent to the receptor molecule. These changes eventually lead the brain cell to electrochemically fire. The firing of multiple brain cells in various areas of the brain affects what we experience as sensations, thoughts, and feelings.
There are literally dozens of chemicals that may serve as neurotransmitters in various parts of the brain. However, in relation to mood change, it appears that there are primarily four neurotransmitters in two major classes—the up or excitatory neurotransmitters, and the down or de-excitatory neurotransmitters.
Three primary excitatory neurotransmitters -- norepinephrine (NE), serotonin (5HT) and dopamine (DO) -- and only one primary de-excitatory neurotransmitter -- gamma aminobutyric acid (GABA) -- have been identified to date. The interaction of these neurotransmitters with their potential receptor sites is extremely complex. Each neurotransmitter binds to at least two, and in some cases several, different receptor subsites, and the receptors and neurotransmitter molecules themselves are distributed in varying ratios in various parts of the brain. This is why understanding how the brain works is so challenging and why it is one of the key areas of modern scientific research, with new knowledge -- and consequently new chemical treatment approaches -- emerging literally on a monthly basis.
The effects of medications on the brain depend on how well and where in the brain they mimic the natural neurotransmitter molecules in attaching to the receptor sites. None of the current medications are perfectly similar to the neurotransmitters in how they bind to receptors; furthermore, various chemical components of a single medication may bind to various receptor molecules. These factors give rise to the differences in the spectrum (or range) of actions of antidepressants and other psychotropic medications and in the patterns of side effects from these medications. The same factors are responsible for the differences in the effect of legal and illegal drugs such as alcohol, antihistamines, cocaine, amphetamine, and cannabinoids (marijuana).
Antidepressant medications all work in some way by increasing the amount of active up neurotransmitters, or decreasing the amount of down neurotransmitter in key parts of the brain. Current medications work in one of five ways:
Type 1: block the ability of enzymes, such as monoamine oxidase
(MAO), to break down the up neurotransmitter
Type 2: block reuptake of the up neurotransmitter into the neurons
Type 3: block the down neurotransmitter receptor site
Type 4: stimulate production or release of up neurotransmitter
Type 5: mimic the up neurotransmitter by binding to receptor
