How we got here
In the early 1900s, doctors attempted to solve melancholia—the first term for depression—through electroshock treatments and herbal remedies. After decades of failed attempts, they accidentally stumbled on a new hypothesis. While administering tuberculous drugs, doctors observed surprising mood-elevating effects in their patients. Based on the discovery, they developed a theory that monoamine drugs, which affect noradrenaline, serotonin, dopamine, and norepinephrine, could also alleviate depression. As a result, pharmaceutical companies in the 1950s began developing new antidepressants drugs to target these biochemicals.
Tricyclic Antidepressants (TCAs)
TCAs are the earliest known monoamine antidepressant drugs, which work primarily by boosting happy hormones, such as serotonin and norepinephrine. While effective at elevating mood, TCAs may also cause severe side effects, including significant drops in blood pressure, difficulty urinating, sexual dysfunction, and tremors. As a result, TCAs have primarily been replaced by antidepressants that are supposedly safer and more effective. Despite the rhetoric, research shows patients are only negligibly more satisfied with today’s alternatives.
Monoamine Oxidase A Inhibitors (MAOIs)
Along with TCAs, psychiatrists often prescribed MAOIs to treat the chemical imbalances they believed caused depression. MAOIs work by blocking monoamine oxidase, the enzyme that diminishes happy hormones in the brain. While successful at a chemical level, MAOIs are incompatible with the standard American diet of red wine and beer. Mixing the two can trigger a spike in blood pressures as well as seizures. Starting in the late 1960s, pharmaceutical companies began developing SSRIs.
Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs are the most recent psychiatric medicine, touted as a revolutionary approach to boosting serotonin levels. But the fact is scientists don’t truly understand how SSRIs work on a neurochemical level. When compared to TCA antidepressants, research shows SSRIs do not exhibit statistical improvements in treating depression. According to a meta-analysis of multiple antidepressant medications, SSRIs are only slightly more effective than placebos. Moreover, depressed people who take SSRIs report a slew of unwanted effects, from sleep issues to anxiety to suicidal behavior and severe dependency. The facts speak for themselves. The time was yesterday for mental health professionals to consider ketamine therapy as an alternative treatment for depression.
Ketamine therapy and consciousness
Mounting evidence shows ketamine may work by modulating glutamate, a neurochemical in the brain associated with depression. Ketamine is also known to have “neuroplastic effectiveness,” which can create new brain pathways.
Through this mechanism, ketamine can rewire the brain and change the mind by allowing people to dissociate from worry and detach from formerly limiting beliefs, opinions, and habits. Ketamine creates shifts in perspective everyone knows they need but can’t seem to access through brute prescription force. Even with a conservative dose, ketamine can yield physical and mental perception changes that allow patients to explore hidden parts of their consciousness.
The numbers tell the story
The first placebo-controlled double-blind ketamine therapy trial in 2000 showed that subjects treated with ketamine experienced a significant reduction in depressive symptoms. The placebo group did not.
A second randomized controlled trial in 2006 showed a single ketamine injection could produce significant depression relief within 110 minutes in more than 70% of patients.
In that same study, one-third achieved clinical remission in 24 hours.
Another study with treatment-resistant patients found ketamine diminished suicidal thoughts within 24 hours.
How we got here