Even as depression rates continue to rise in America, the drugs that are used to treat the illness haven't change much in decades.
Almost all of them target a brain chemical called serotonin that helps brain cells (neurons) talk to each other.
By increasing access to the vital neurotransmitter, it is thought that healthy communication can be restored.
There's only one problem: serotonin is only present in about 5 percent of neurons.
That may be why most antidepressants take several weeks to reach their full therapeutic effect.
As early as the 1950s, antidepressants were used to treat mood disorders by targeting the monoamine system, including neurotransmitters like dopamine, norepinephrine, and serotonin.
Their efficacy has been well established, but is certainly not unchallenged.
In recent years, a new class of drugs that target a different chemical called glutamate has forced the psychiatric community to reexamine their allegiance to the old standbys.
What is glutamate? The main reason increasing or enhancing levels of serotonin in the brain may be effective is that the chemical helps regulate our moods through constant communication.
When there is an interruption in service, however, we may experience bouts of anxiety, depression, and other mood disturbances.
A far more plentiful neurotransmitter, glutamate is used in over half of the synapses in our brains.
Working in conjunction with GABA (gamma-aminobutyric acid), glutamate plays a role in many brain process, including the overall level of excitation.
The simplest way to explain their relationship is to think of a stoplight and how it controls traffic.
Because glutamate is excitatory, it would be the green light, while the inhibitory GABA would be the red light.
When working correctly, the pair keeps traffic humming along by regulating numerous processes with their "stop" and "go" signals.
But when one or both lights malfunction, chaos occurs, i.
e.
, the brain becomes unbalanced.
The disorders and illnesses that inevitably ensue almost always effect our moods.
Glutamate and depression As amazing as it may sound, it took a long time for the scientific community to confirm that glutamate was indeed a neurotransmitter.
One of the standard 20 amino acids that are used to make proteins, the incredible chemical carries more messages in the brain than any other.
Its effect is felt every time we ingest caffeine, which increases glutamate activity; and also when we drink alcohol, which decreases glutamate activity.
But is it the secret to treating depression? Because scientists took so long to identify glutamate as an neurotransmitter, their understanding of the role it plays in psychological disorders is tenuous, at best.
By comparison, researchers have been studying serotonin's role in depression since the 1950s! What many have only recently been forced to accept is that the disorder is far more complicated than a biochemical imbalance, i.
e.
, low serotonin levels.
What is interesting and exciting about drugs that target glutamate is that they may provide nearly immediate relief.
The research Often described as "new" research because it was not discovered decades ago, brain imaging in patients with depression has implicated possible defects in the glutamatergic systems.
Research also suggests that certain antidepressants may make it easier for neurons to send and receive glutamate.
How would this help? While it is merely a hypothesis at this point, investigators believe that people who suffer from clinical depression have lower glutamate levels in an area of the brain called the anterior cingulate cortex.
They also speculate that these depressed individuals have fewer functioning glutamate receptors across many regions of the brain.
Treatment options About ten percent of adult Americans, or roughly twenty-five million people, are currently taking antidepressants.
But according to findings from the largest clinical trial of major depressive disorder (MDD) on record, just one in three patients fully recover by taking antidepressant medications.
These results are obviously important because they demonstrate how ineffective current pharmacological treatment options are when it comes to the most serious type of depression.
But more exigent even than the potentially low efficacy rates of drugs that target serotonin is the delayed onset of antidepressant effects.
Because certain types of depression are associated with much higher rates of suicidal ideation, doctors need treatment options that are fast-acting, since any delay could be fatal.
For these high-risk patients, traditional antidepressants are wholly inadequate.
They are really only administered because they are the only available option...
until now! What is tianeptine? Discovered and patented by a French pharmaceutical company in the 1960s, tianeptine is a tricyclic antidepressant that was thought to serve as a selective serotonin reuptake enhancer (SSRE).
But recent researcher has confirmed that the drug does not target serotonin as originally assumed.
Rather, its antidepressant effects are the result of indirect alteration of glutamate receptor activity, altered neuroplasticity, and the release of brain-derived neurotrophic factor (BDNF).
In other words, it's mechanism of action is far more complicated than it seemed.
The reason tianeptine was mislabeled is simple: researchers didn't known that glutamate was a neurotransmitter.
As such, they simply assumed that any drug with demonstrable antidepressant effects targeted serotonin.
Though the error was a costly one, setting back research on the drug several decades, its reemergence as a different kind of antidepressant is exciting news for people struggling with depression.
Why? New theories about depression Traditional antidepressants were developed based on the monoamine hypothesis, which stated that depression was the result of chemical imbalances in the brain.
By increasing the levels and/or the effectiveness of neurotransmitters like serotonin, dopamine, and nnorepinephrine, scientists believed that healthy communication could be restored.
And while this hypothesis still holds, contemporary theories suggest that the impairment of neuroplasticity and cellular resilience also play a part in depression.
What does this mean? Neuroplasticity is defined as the ability of a brain to adapt both functionally and structurally to stimuli that is created by a depressive illness.
Whether caused by an imbalance of certain chemicals or some other unknown factor, brain imaging reveals that people with depression undergo structural changes to the hippocampus, prefrontal cortex, and amygdala regions of the brain.
Tianeptine prevents unhealthy alterations by triggering a series of cellular adaptations that protect neurons from the harmful effects of chronic stress.
Numerous studies have noted a substantial reduction in neuroplasticity in patients taking tianeptine for long-term treatment of clinical depression.
Conclusion To say that tianeptine has revolutionized the study and treatment of depression would be premature.
But researchers are excited about its unique clinical and pharmacological properties.
The little-known drug is changing the way the psychiatric community thinks about depression.
Instead of simply blaming chemical imbalances in the brain for this incredibly complex, increasingly common disorder, they are now considering more comprehensive theories that may lead to a better understanding of the disease.