Can Ketamine Really Treat Depression?


What is Ketamine?
Ketamine is a sedative, and until recently was commonly used in veterinary medicine to sedate horses and other large animals. Ketamine has historically been used to provide pain relief and sedation, and also to start and maintain anesthesia. In recreational settings it’s common as a club drug because it causes effects like delirium or a sense of disconnection from one’s body. A side-effect of its overuse is referred to as being stuck in a “K-hole.”
Other Possible Applications of Ketamine
Recently, some in Silicon Valley began promoting ketamine’s brain-boosting effects, and scientists caught wind of another possible application: a treatment for depression.
Researchers at the University of California, Davis began studying the drug, and found that there might actually be some truth behind the hype. Their study found that common psychedelics like ketamine, LSD, and MDMA literally change the structure of our brain’s neurons — something akin to tweaking the underlying circuits that can the cause mental health disorders.
Research on Ketamine
“People have long pretended that the psychedelics are efficient
of altering the neuronal structure, but this is the first study that clearly and precisely supports that hypothesis,” said David Olson, an assistant professor in the university’s chemistry, biochemistry, and molecular medicine departments and the leader of the research team. “The rapid effects of the ketamine on mood and plasticity are truly astounding.”
Ketamine’s club-drug party days may give it a bad rap, but very early research looks promising for those truly suffering from treatment-resistant depression — and entrepreneurs are naturally eager to cash in. The San Antonio-based Kalypso Wellness Centers offer $495 ketamine infusions, and the company’s success has been copied by a number of other clinics.
Caution on Ketamine hype

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First, the clinics offering these services are often unlicensed and lack an on-site psychiatrist. They’re frequently prescribing off-label uses of ketamine that haven’t been rigorously studied. In addition to depression therapies, some advertise ketamine solutions for lupus- and cancer-related concerns.
It’s also important to note some of the common side effects of ketamine include dissociation and sedation, and there are specific subsets of patients for whom its use might be especially dangerous, including those with unstable or poorly controlled hypertension or with pre-existing aneurysmal vascular disorders.
But it’s clear that those who are suffering from treatment-resistant depression are clamoring for ketamine treatments, and the government is listening to those concerns. The benefits of the drug are so encouraging that the U.S. Food and Drug Association (FDA) recently approved a version of the drug for use as an “adjunctive therapy” for depression — meaning used in addition to the primary treatment method.
A New Option for Sufferers of Treatment-Resistant Depression
The new drug, Spravato — or esketamine, half of the ketamine molecule — has some interesting rules that likely arise from ketamine’s past as a club-kid. First, it’s a nasal spray, and patients must be taking another antidepressant to get a prescription. And you can’t simply drive to your favorite drug store to pick up your prescription. You’ll need to visit certified Spravato-dispensing clinics.
Spravato won’t be cheap, either: patients can expect to pay from $590 to $885 per dose, and many will require once – or twice per weekly treatment. That cost adds up very fast — but if the drug successfully addresses treatment-resistant depression, it may be something that more are willing to explore.
And research says there may be reason for optimism. A double-blind, doubly randomized, delayed-start, placebo-controlled study of the 126 adults has showed some efficacy of Spravato in a longer-term maintenance-of-effect trial. According to a report from the FDA: “In one of the short-term studies, Spravato nasal spray demonstrated statistically the significant effect compared to placebo on the severity of depression, and some effect was seen within the two days. The two other short-term trials did not meet the pre-specified statistical tests for demonstrating effectiveness.”
Much more research on ketamine is needed, but early results are intriguing. But before exploring your own therapeutic regime, make sure to talk with both a licenced, qualified therapist as well as a doctor. They can help determine if your unique constellations of mental health needs would necessitate an intervention of this nature, and make sure you’re using the drug safely and appropriately.
How does ketamine work?

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It’s not entirely clear how ketamine works. Because it exerts an antidepressant effect through a new mechanism, ketamine may be able to help people successfully to manage depression when other treatments have not worked.
One likely target for the ketamine is NMDA receptors in the brain. By binding to these receptors, ketamine appears to increase the amount of a neurotransmitter called glutamate in the spaces between neurons. Glutamate then activates connections in another receptor, called the AMPA receptor. Together, the initial blockade of NMDA receptors and activation of AMPA receptors lead to the release of other molecules that help neurons communicate with each other along new pathways. Known as synaptogenesis, this process likely affects mood, thought patterns, and cognition.
Ketamine also may influence depression in the other ways. For example, it might reduce signals involved in the inflammation, which has been linked to mood disorders, or facilitate communication within specific areas in the brain. Most likely, ketamine works in several ways at the same time, many of which are being studied.
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