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Our knowledge of the world and how it works is constantly developing as we study it through science. We now know that the world is round, for example. We no longer rely on leeches to reduce fevers. And people are generally living longer thanks to the many medical discoveries in the last 50 years alone.

The study of depression and the brain’s influence on it has also advanced rapidly – though much about the brain’s function remains a mystery. But from the introduction of the first anti-depression drug to the latest discovery of ketamine infusions to treat depression, the medical community’s knowledge of depression and its causes is only continuing to grow.

Here, you will find a brief history of popular depression treatments and the corresponding breakthroughs in brain science they have caused. For a more in depth analysis, we recommend that you read this article about the history of depression treatments.

Depression History

Initial Theories on the Mind-Mood Relationship: Serotonin Levels?

In the 1950s, doctors treating tuberculosis noticed that a drug called iproniazid caused their ill and depressed patients’ moods to elevate. A few years later, another drug called Raudixin (prescribed to treat blood pressure) created “blue feelings” in patients. To explain why these drugs affected moods, psychiatrists hypothesized that depression is caused by a “chemical imbalance” in the brain – specifically, low serotonin levels.

So, pharmaceutical chemists began developing drugs that would elevate serotonin levels. The mid ‘70s saw the creation of Prozac, Paxil, and Zoloft – some of the most commonly prescribed anti-depression drugs.

Ketamine for Chronic Pain

Inconsistent Research to Back Up Serotonin Hypothesis

While these medications seemed to help many people, studies conducted in 1975, 1987, and 1994 produced inconclusive and contradictory evidence that low-serotonin levels are the actual culprits behind depression. Further studies showed conflicting evidence that serotonin-increasing medications worked better than placebo.

In 2010, researchers found that antidepressants barely affected patients struggling with mild depression. But in patients struggling with the most severe forms of depression, antidepressants were substantially more beneficial than placebo.

The overall conclusions? First, patients with severe depression respond most strongly to antidepressants. Second, serotonin levels play a role in those responses. Third, the theory that serotonin levels are the sole determining factor for depression cases was insufficient. 

Neural Development and Antidepressants

Research in the 1980s from neuroscientist Fred Gage began to suggest that new nerve cells can be developed in a section of the brain called the hippocampus. This research was revolutionary because scientists believed at the time that adult brains were incapable of further cell development. The hippocampus is the sector of the brain that stores memories and affects emotions.

Gage and his team tested this theory on mice. Chronically stressed mice developed anxious and depressed behaviors simultaneously with reduced nerve cells in the hippocampus. After removing the chronic stress, hippocampus cells began developing and depression symptoms significantly reduced.

Another neuroscientist named Rene Hen furthered Gage’s experiments by feeding mice Prozac and, more recently, testing depressed monkeys. His experiments suggest that antidepressants like Prozac and Zoloft produce the most effect by increasing serotonin levels in conjunction with neural development in the brain. Which may explain why antidepressants take a few weeks to start working – building new neural “circuits” takes time.

Depressed girl image

Depression Research: A Current Theory

The current theory on how depression interacts with the brain recognizes that our brains are complex and depression is often more involved than “your serotonin levels are low.”

Researchers suggest that some depression may occur when something like stress or genetics causes nerve cells in the hippocampus to die. This death disrupts signaling to our “mood circuit,” so emotions get recognized as grief or anxiety. The “mood circuit” – known scientifically as the subcallosal cingulate – is affected by serotonin levels (so the serotonin theory wasn’t completely wrong, just too simple).

Antidepressants like Prozac do more than strengthen signals by increasing serotonin levels. They actually help to rewire the brain’s mood circuit by causing nerves to grow.

But researchers recognize flaws in this theory and that depression is complicated and different for each individual – so one theory is unlikely to explain every depression case. Which is also why some depression treatments work from for some people, but not for others.

Ketamine Molecule

Where Does Ketamine Fall Into This Research?

Ketamine has successfully treated treatment resistant depression with 70% of those treated with ketamine reporting that they feel “happy.” In concurrence with current theories, ketamine infusions work to “rewire” the brain. Carlos Zarate, from the Mood and Anxiety Disorders Program at NIMH, and a team of fellow researchers studied Ketamine’s affect on patients with depression. They found that Ketamine changed brainwave activity, indicating that Ketamine improved neural connectivity.

Not only do Ketamine infusions work to “rewire” neural connectivity, they also work rapidly with many patients reporting improvement after the first treatment. And Ketamine infusions last longer than typical anti-depressants because it has a greater and longer-lasting affect on lipid rafts and G-proteins – necessary for neural messaging.

Ketamine Infusions for Depression.

Are you or someone you know struggling with severe depression? Ketamine infusions could help. 70% of patients treated with Ketamine infusions say they finally feel happy. And many find relief after the first treatment.

Virginia Infusion Therapies, located in Loudoun County, is Virginia’s leading provider of Ketamine Infusions for depression and pain conditions. If you want more information about Ketamine Infusion therapy, please contact us to set up a free consultation.

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Phone consultations only take about 15 minutes with a doctor from Virginia Infusion Therapies. Learn more about how ketamine solves for 70% of depression patients and can solve for you.