What Is Ketamine Therapy, and How Does It Work for Depression? Here's What to Know

Kaitlin Vogel
·6 min read
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Since depression comes in many forms, treating this mental health condition isn’t a one-size-fits-all approach. With a wide variety of treatment methods, it can take time to find the one that works best for you.

One type of therapy that has been gaining traction in the medical community is ketamine therapy. But what is ketamine? Originally used as an anesthetic for many years, ketamine is now being recognized for its ability to improve mental health.

In fact, researchers at the Yale School of Medicine discovered that one subanesthetic dose of ketamine reduced symptoms of depression and in some instances led to nearly a full recovery in less than one day.

What Is Ketamine Therapy?

Ketamine has been widely used around the world as an anesthetic for 60 years—and is still widely used today for that purpose. About 20 years ago, growing evidence showed ketamine to be an effective and fast-acting antidepressant.

In doses that are much smaller than the dose used for general anesthesia, ketamine has now been shown to be effective for depression, anxiety, PTSD and other mental illnesses, Dr. Mike Dow, PhD, PsyD, Field Trip psychotherapist, explains. Initially, ketamine for depression was primarily delivered intravenously. Then, scientists discovered that different delivery methods of ketamine allowed for simultaneous psychotherapy.

In ketamine-assisted psychotherapy (KAP), intramuscular injection (a quick and fairly painless shot with a small needle) and oral delivery (taken by mouth) of ketamine allow for concurrent psychotherapy alongside the medicine and also don’t require the needle to remain in the patient’s arm for the whole session. This combination of ketamine and psychotherapy solved one of the biggest downsides of ketamine therapy—while IV ketamine therapy is remarkably effective, research shows it only lasts about a month. When combined with psychotherapy, it lasts three to four times longer, Dr. Dow adds.

Related: 21 Things You Should Never Say to Someone With Depression (and What to Say Instead)

Ketamine has been used primarily for anesthesia, which is why it will also benefit people living with anxiety. Ketamine treatment is a preventative treatment for anxiety, so it will be best utilized to treat generalized anxiety disorder, Dr. Julian Lagoy, MD, a psychiatrist with Mindpath Health, explains.

There are various approaches available today for ketamine therapy, including IV infusion, intranasal spray, sublingual, intramuscular injection, and oral or rectal. The IV infusion is the most common ketamine therapy, as it is the most studied and safest method for administering ketamine.

How Ketamine Therapy Works To Treat Depression

In many ways, ketamine is a functional approach to depression.

The old monoamine hypothesis of depression was formulated in the 1950s and states that depression is the result of low levels of the monoamine neurotransmitters: serotonin, dopamine and/or norepinephrine, Dr. Dow states. This is the philosophy that is the underpinning of most major psychotropic medications like SSRI antidepressants (that “boost” serotonin), SNRI antidepressants (that “boost” serotonin and norepinephrine) and Wellbutrin (that “boosts” dopamine).

Ketamine works in very different ways. First, it’s not targeting the serotonin pathway.

It works via the glutamate pathway, Dr. Dow says. Glutamate is the most abundant excitatory (“turning up”) neurotransmitter in the central nervous system. But like those older antidepressants, ketamine has “downstream” effects on the monoamine neurotransmitters; it will increase levels of dopamine and serotonin.

In terms of targeting the root cause, Dr. Dow explains how ketamine therapy works:

1. It relieves inflammation in the brain, and neuroinflammation has been linked to many mental illnesses.

2. It helps the brain to form new connections.

3. It helps to create new brain cells by boosting brain-derived neurotrophic factor (BDNF) which has been dubbed “Miracle-Gro for the brain.” Atrophy in the brain (which is a result of everything from a bad diet to aging itself) has been linked to depression.

4. It is a mild empathogen and is “heart opening." When combined with psychotherapy, it can allow a patient to put down their defenses and address the root of their mental illness with their therapist.

Related: 82% of People Now Believe Mental Health Is Just As Important As Physical Health, so Here’s How to Find the Right Therapist For You

Side Effects and Risks of Ketamine

The most common side effects are nausea and an increase in blood pressure.

This is why Zofran (an anti-nausea medication) and ginger tea are typically offered to patients, Dr. Dow says. Blood pressure is also monitored and it is not used when a patient has uncontrolled hypertension. Since it rapidly increases dopamine, Dr. Dow says they do not treat people who are psychotic (e.g., schizophrenia, bipolar) since a rise in dopamine will make psychosis worse (psychosis is associated with excess dopamine).

Most of the other “side effects” like dissociation (the feeling of leaving the body), “dreaming” or hallucinations are actually harnessed as part of the psychedelic experience that can help people with depression and other mental illnesses.

There may be some anxiety alongside the novel psychedelic experience, but doctors help people manage this with personalized and dose discovery (for example, if a person has never taken a psychedelic and feels anxious about it, they would start with a very low dose for session one and gradually increase the dose). The other major side effect seen in high-frequency recreational ketamine users is damage to the bladder, but that isn't seen often, Dr. Dow adds.

How Long Does It Take To See Results on Ketamine?

"We recently surveyed patients and reported that it helped 93% with anxiety and 92% with depression. There were sustained improvements in their symptoms immediately after one session, with benefits lasting for as long as 120 days," Dr. Dow shares.

One of the best things about ketamine is that the reduction in depression is evident within four hours of the first session. Think about how many people suffer while in a depressive episode: With most antidepressants and standard talk therapy, they have to wait weeks or months to find relief. This is one of the most groundbreaking differences—ketamine therapy can help people find relief from depression fast, Dr. Dow explains.

Are Some People More Likely to Benefit From Ketamine Therapy Than Others?

Ketamine is a proven effective treatment for mental health afflictions like depression, anxiety and PTSD, and can help heal trauma. It is even effective for treatment-resistant depression and works when multiple prescription antidepressants have failed.

"We believe that anybody can benefit from ketamine-assisted therapy as it can aid in self-discovery, help improve your relationship with yourself and others, help break unhealthy thought patterns, spark creativity and so much more," Dr. Dow says.

Interestingly, there is some research that shows that people with certain personality traits can tolerate higher doses faster. A person with low levels of neuroticism and high levels of openness is likely to tolerate a higher dose in session one than someone who is very neurotic, for example. There are IV ketamine clinics that dose based on weight, but Dr. Dow says that they spend time getting to know their patients before the first session and find that personalized dose for each person.

It is important to note that ketamine therapy is contraindicated in those who had a previous bad reaction to the drug, and it is not recommended in pregnancy or breastfeeding, says Dr. Lagoy. Ketamine therapy is also contraindicated in schizophrenia.

Next up: Here's What Major Depressive Disorder Actually Is—and How It Differs from 'Regular' Depression

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