What You Need to Know About Ketamine for Depression

What You Need to Know About Ketamine for Depression

By Melissa Quinn, MD

Depression is taking a devastating toll on humanity. Worldwide, depression is the third leading cause of disability. In the U.S., it’s affecting a skyrocketing number of people. During the pandemic, Census Bureau Statistics on 42,000 people found that 24% of respondents reported significant symptoms of major depressive disorder. Among 18-29-year-olds, the number was even higher with 36% reporting depressive symptoms.

This common condition can have devastating consequences—causing problems with energy, focus, motivation, sleep, appetite, libido, and more. Some people are left feeling so helpless and hopeless, they develop suicidal thoughts and behaviors. Suicide is the 10th leading cause of death in the U.S. In 2018, 48,344 people in the U.S. died by suicide and there were 1.4 million suicide attempts. That boils down to an average of 3,836 attempts per day.

The Traditional Approach to Treating Depression

For decades, pharmaceutical antidepressants have been the primary medical intervention for depression (outside of lifestyle interventions such as dietary changes, exercise, and mind-body practices). Typically, it takes 4-12 weeks of use for patients to experience a decrease in symptoms. Unfortunately, 30%-60% of individuals do not respond to SSRIs (though there are genetic tests to help identify these clients and therefore help with improved treatment decisions).

Some people try several different antidepressants without relief, leading to a form of depression known as treatment-resistant depression (TRD). This often leads to months of inadequate medication treatment that can leave the person feeling more hopeless than prior to starting treatment.

Considering the dire statistics and the shortcomings of antidepressant medications, it’s clear that we are in desperate need of more effective treatments for depression and suicidal ideation.

Ketamine: A Potential Breakthrough

Increasingly, psychiatrists are turning to ketamine as another option. Used as an anesthetic drug for about 50 years, it deadens pain and can cause feelings of being dissociated from one’s own body. A growing body of scientific evidence, including a 2017 study in the Journal of Clinical Psychiatry, has found that ketamine has antidepressant effects. And it enhances mood much more quickly than traditional antidepressants. A 2018 review of over 20 studies on ketamine in Drug Design, Development, and Therapy showed that it produces significant decreases in depressive symptoms in just 24 hours.

Here’s what you need to know.

Mechanisms of action: Unlike traditional antidepressants that affect neurotransmitters, including serotonin, dopamine, and norepinephrine, ketamine works differently. It is an agonist of the N-methyl-D-aspartate (NMDA) receptors, which work on the glutamate neurotransmitter systems. Although the full mechanism that ketamine induces is not fully understood, we do know that it increases levels of brain-derived neurotrophic factor (BDNF), which plays a role in the growth and maintenance of neurons.

Types of ketamine delivery: Ketamine can be delivered in a variety of ways, and each route differs in its bioavailability. The rates are:

Intravenous: 100%

Intramuscular: 93%

Intranasal: 25-50%

Sublingual (under the tongue): 30%

Orally (by mouth): 16-24%

Psychotherapy-assisted delivery vs. IV therapy only: Ketamine encourages open-mindedness, however, it’s the therapist who enhances this effect by doing deeper integration work to promote growth and change. With this guided process, patients can weave the experience into their daily life to support long-term change. In some places, ketamine IV therapy is being offered alone without psychotherapy, but the doses are very small, and it doesn’t offer the added benefits of working with a mental health professional.

Frequency: Ketamine is typically administered during psychotherapy sessions that last 2-3 hours each with 2 sessions per week for 3 weeks.

Consider set and setting: A patient’s mindset is a critical element to consider for any psychiatric experience, and ketamine administration is no different. Be sure your patients have realistic expectations regarding what to expect during the process and make the setting a comfortable one.

Not a solo treatment: Some patients may look to ketamine as a sort of “magic bullet” that can eliminate depressive symptoms. As mental health professionals, it is up to us to inform patients that ketamine will be most effective when it is part of a comprehensive treatment plan that includes brain healthy lifestyle changes, nutritional supplements, psychotherapy, and more.

Side effects: Ketamine’s safety and tolerability have been demonstrated over nearly 50 years. Side effects may include dizziness and a rise in blood pressure. As such, individuals with severe hypertension or heart disease are not good candidates.

Potential for addiction: A 2018 study in the American Journal of Psychiatry found that ketamine’s antidepressant effects activate the opioid system, but decades of research show that ketamine is not physically addicting. However, it can be used inappropriately. For this reason, it is best used only in a clinical setting where the administration is monitored by a healthcare professional.

Other issues that may respond to ketamine: In addition to effectively treating depression, ketamine may also be helpful in treating anxiety, post-traumatic stress disorder (PTSD), emotional trauma, and addictions.


About the Author: Melissa Quinn, MD, Amen Clinics Los Angeles

Dr. Melissa Quinn is a psychiatrist who is double board-certified by the American Board of Psychiatry and Neurology. Her passion is to help people heal, get psychologically well, find the relief they deserve, and help them to become the best version of themselves. She helps children, adolescents, adults, and families get their lives back on track with a whole-person—and when appropriate—a whole-family approach. By developing her clients’ inner strengths, she shows them how to reach their highest potential.

She knows that people are seeking a range of solutions for prevention, health, and healing. As a result, Dr Quinn became passionate about learning integrative approaches and was subsequently board-certified in Integrative and Holistic Medicine through The Academy of Integrative Health and Medicine. She later went on to peruse a fellowship in Transcranial Magnetic Stimulation (TMS) through Duke University and Ketamine Assisted Psychotherapy through PRATI (The Psychedelic Research and Training Institute). She enjoys working with a variety of clients, but she specializes in working with patients with ADHD, depression, anxiety, panic disorder, obsessive-compulsive disorder, and posttraumatic stress disorder.


  1. How about Low dose Naltrexone for Chronic Pain? Functional Medicine teaching is excited about that as well. They by stopping the pain but also still stimulate the Opiod Receptors it is functionally an Anti-depressant safe than Neurotoxics.
    Your thoughts? Feel free to email. I’m an Amen groupie. Two scans. Practitioner course twice.

    Comment by William Kelso, II — October 20, 2020 @ 12:49 PM

  2. I found it helpful when you said that ketamine could be more effective when combined with psychotherapy sessions and other comprehensive treatment plans. This is something that I will share with a friend who has been wanting to find a way to ease her depression problems. She mentioned last night over dinner that her mental health problems have started since she lost her job last year.

    Comment by Shammy Peterson — April 5, 2022 @ 2:01 PM

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