What is Ketamine: How It Works and Why It Can Treat Severe Depression?

Ketamine is both a valuable anesthetic and a potentially harmful street drug when misused, but did you know that ketamine is a proven treatment for depression, too? A Schedule III drug, ketamine, can cause you to feel detached or dissociated from the world around you. Depending on the dose and manner in which you take it, ketamine can be a sedative or simply make you feel sleepy. It can also cause hallucinogenic effects. So, how does ketamine work as a treatment for depression?

How Ketamine Works

Used as a treatment for severe depression since around 2009, ketamine treatment is believed to help with depression by acting on the body’s glutamate system and helping rebuild pathways in the brain.

Glutamate is one of the brain’s main chemical messengers, or neurotransmitters. It is usually excitatory, which means it stimulates brain cells. Glutamate also helps to regulate signaling in the GABA system. GABA is gamma-aminobutyric acid, which is an inhibitory neurotransmitter, and generally reduces signaling.

Researchers believe that glutamate and GABA work together to regulate much of our brain activity, including mood. Stress and depression are associated with altered glutamate signaling and also result in a reduction in the number of synapses and other connections in the brain. This is where ketamine comes in.

Ketamine has been shown to quickly stimulate glutamine signaling and restock glutamate receptors, allowing the brain to form new synapses. The boost in glutamine signaling results in a release of many neural growth factors. These molecules, called neurotrophic factors, stimulate the growth of new connections, including new synapses. This is the action thought to be behind the reason that ketamine is so effective for depression.

Thanks to this antidepressant effect, ketamine has been used off-label (without FDA approval) as a treatment for depression. However, this type of treatment with ketamine (usually intravenous, sometimes by other routes) uses the same kind of ketamine used for anesthesia, albeit at lower doses. Although it works, its use for depression is generally not covered by insurance.

The only type of ketamine treatment for depression with FDA approval is esketamine nasal spray. Esketamine, which goes under the brand name SPRAVATO®, is FDA-approved for treatment-resistant depression (TRD) and major depressive disorder (MDD) with suicidal ideation. Esketamine binds more tightly to glutamate receptors than racemic ketamine, making it more potent at a lower dose.

What Does Ketamine Treatment Look Like?

Ketamine is usually given through an IV for intramuscular injection (IM). Ketamine IV treatment can make you feel “loopy,” dizzy, or nauseated, although the effects tend to wear off within about two hours.

For the FDA-approved SPRAVATO® treatment, you’ll need to visit a center certified by the REMS ( Risk Evaluation and Mitigation Strategy) program. At the REMS-certified center, you’ll have a consultation with a provider. If you move forward with treatment, then at our next visit, you’ll receive your first dose of SPRAVATO®. Your provider will advise you not to eat for two hours and not drink fluids for 30 minutes before you come in.

When you visit the center or provider’s office for the second time, you’ll be given instructions on administering the nasal spray to your nostrils. Your provider will help you get settled in a quiet space and ask you to complete a depression scale before directing you to take your dose kit. At any REMS-certified center, you’ll have your blood pressure taken several times and be monitored throughout your mandatory two-hour waiting period.

Like ketamine, esketamine can make you feel dissociated, dizzy, and nauseated. These side effects tend to peak within two hours, but to be safe, you must have a prearranged ride home and are not allowed to drive yourself away from your treatment center. Patients may start to feel the positive effects of esketamine treatment for severe depression within hours after treatment.

Is Ketamine or Esketamine Treatment Covered by Insurance?

Because it’s an off-label use of ketamine, IV treatment isn’t covered by insurance and can get pricey. On the other hand, esketamine nasal spray does have FDA approval for difficult-to-treat depression, which means it is normally covered by insurance.

Treatment with esketamine is usually twice per week for the first four weeks and then once per week for the next four weeks. After that, the schedule varies, depending on your response to the medication. And again, normally, these treatments would be covered by your insurance.

Ketamine Treatment for Severe Depression

Thanks to the way it acts quickly on the brain and helps build new neural pathways, ketamine plays a major role in treating severe depression. With esketamine nasal spray or ketamine treatment, patients do not have to wait weeks to see if a standard antidepressant works to ease their symptoms.

It’s important to note that the FDA requires patients to take an antidepressant alongside their esketamine treatment for depression. If you believe ketamine treatment for depression could help your symptoms of treatment-resistant depression or major depressive disorder, talk to your doctor about ketamine IV therapy or esketamine (SPRAVATO®) nasal spray and other treatment options.

If you or someone you know experiences mental health issues, it is important to seek help from a qualified professional. Our Resource Specialist can help you find expert mental health resources to recover in your community. Contact us now for more information on this free service to our users.

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About the Author: Dr. Steven Harvey joined Greenbrook TMS in March 2018 as Regional Medical Director of our Greater St. Louis region. He is board certified in general psychiatry and has been practicing since 1996 since earning his medical degree from the Washington University School of Medicine in St. Louis. Dr. Harvey’s interest in TMS therapy was first sparked during his residency, and in 2013 he began practicing TMS therapy.

Photo by Valdemars Magone on Unsplash

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