Antidepressants on a molecular level

In last week's column I covered the reasons why antidepressants are not considered dependency-forming even though they are associated with withdrawal symptoms. Today I'd like to spend a little more time discussing how these medications work in our brains to treat mood and anxiety disorders.

Antidepressants are prescribed by the millions in North America and there is a general misunderstanding about what they do in the brain. Many people seem to think of these drugs as 'happy' pills or narcotics and don't trust the medical community's ability to administer them appropriately.

Before examining exactly what antidepressants are doing in the brain, it is important to understand what is going wrong when a mood disorder occurs.

Although the exact answer to this question is not fully understood, it is known that genetic and environmental factors work together to create a physiological change in the depressed brain.

Different cells in the body communicate with one another by means of chemicals called neurotransmitters. There are many different types of neurotransmitters at work throughout the body and it seems clear that some of these are not working properly in the brains of people with mood disorders.

In particular, the neurotransmitters serotonin and norepinephrine do not seem to function correctly in depression.

While there are many different kinds of antidepressants available, all of them work by altering the way these chemicals transmit signals between cells in the brain.

In fact, all antidepressants affect one or more of the neurotransmitters - serotonin, norepinephrine or dopamine.

These neurotransmitters are involved in many body systems, but play a particularly important role in mood and the body's response to stress.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin/norepinephrine reuptake inhibitors (SNRIs) are the most commonly used antidepressants today.

SSRIs block serotonin transport and are very successful in the treatment of depression. SNRIs block both serotonin and norepinephrine and are also very effective.

Blocking serotonin works because the concentration of serotonin in the connections between neurons (called synapses) is controlled directly by its reuptake into the neuron. Blocking this reuptake alters the concentration of the chemical and affects the mood and stress response. They work by selectively binding to the carrier that transports serotonin back into pre-synaptic storage sites. This allows more time for serotonin to bind to receptors in the synapse as it is supposed to do.

Older antidepressant medications called tricyclic antidepressants (TCA) also affected serotonin levels, but were not very specific. They altered serotonin levels throughout the body and not only in the mood centres. They also affected several other neurotransmitters and interacted with various other receptors all of which caused unsatisfactory side effects, which is one reason why these are rarely used today.

All of these medications can be effective at treating depression and different people respond to different drugs. By far the most commonly used of them all are the newer medications, which have achieved a better balance between benefits and side-effects.

As medical science improves, the exact mechanisms of action of each drug become a little clearer. There are still some aspects, however, that are not completely understood. For example, we know that SSRIs enhance serotonin transmission, but we are just beginning to get a glimpse of why it needs enhancing and of what effects the neurotransmitters have on genetic expression.

Depressions used to be separated into those that were strictly an illness versus those that were a psychological reaction to various stressors, but this distinction is now obsolete since most depressions involve a little of both to varying degrees.

Although the technical explanations behind the effectiveness of antidepressant medications are interesting, it is not necessary for you to fully understand them in order to receive benefits from treatment. Speak with your doctor if you have further questions or are considering getting treatment for a mood disorder.


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