Ketamine for Treatment-Resistant Depression

What You Need to Know Before Using Ketamine for Depression

nasal spray bottle

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Almost one in three people with major depressive disorder, also referred to as clinical depression, don't find relief from standard treatment methods. This is referred to as having treatment-resistant depression, a condition for which you may be prescribed ketamine.

Research indicates that ketamine can help with treatment-resistant depression, at least in the short term. However, this drug doesn't come without its challenges, including its adverse side effects and the potential for addiction. Here's what you need to know about using ketamine for treatment-resistant depression.

What Is Treatment-Resistant Depression?

While experts don't always agree on how to define treatment-resistant depression, most use this term to describe when a person has tried at least two traditional depression treatments (such as psychotherapy and antidepressants), but failed to achieve positive results after a reasonable amount of time.

To be clear, this doesn't mean that depression isn't treatable. It simply says that a person's symptoms don't improve with standard treatment methods. In cases such as these, both electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) can both help. The problem is that they may not provide relief for several weeks.

This can be discouraging if you're the one with treatment-resistant depression, making you wonder if your feelings will ever go away. It may also help explain why people with treatment-resistant depression have a higher risk of abusing alcohol and drugs, and an increased suicide risk.

Suicide Prevention Hotline

If you or a loved one are having thoughts of suicide, call 911 immediately or call the National Suicide Prevention Lifeline at 988. For more mental health resources, see our National Helpline Database.

Ketamine is a medication-based option for treatment-resistant depression that, unlike ECT and TMS, doesn't require the use of specialized devices. Ketamine also offers patients faster relief, sometimes easing depression after just a single dose (especially if used intravenously).

How Ketamine Helps Treatment-Resistant Depression

Ketamine is a dissociative anesthetic, meaning that it can make you feel detached from your environment while also easing pain. Some research suggests that it is through dissociation that people with treatment-resistant depression find relief, in part, through inducing depersonalization.

Other studies say that it is ketamine's effect on certain receptors in the brain that is responsible for its positive results. Specifically, ketamine is an N-methyl-D-aspartate receptor antagonist and, in this role, provides "rapid antidepressant effects" in people with treatment-resistant depression.

In a study involving 41 people with treatment-resistant depression, a single ketamine infusion decreased 27% of the participants' depression scores by 22.3 points at the 24-hour mark while 5% achieved remission. Each additional infusion decreased participants' depression scores by another two points.

Another study looked at the effectiveness of oral ketamine. This one involved 22 patients who had tried at least three different antidepressant treatments with no effect. Almost one in three (30%) reported that ketamine provided some benefit.

Concerns About Ketamine for Treatment-Resistant Depression

Based on its ability to help ease hard-to-treat depression, it's easy to see why ketamine may be prescribed. Yet, there are a few concerns that exist with this drug.

Illegal Ketamine Use Is on the Rise

Ketamine is a Schedule III controlled substance and is only legal when prescribed by a physician. For instance, in 2019, the U.S. Food and Drug Administration (FDA) approved Spravato—a nasal spray containing esketamine, which is made from ketamine—for treatment-resistant depression.

Yet, the recreational use of ketamine, or its use without a prescription, has increased since 2006, as has its availability. When used illegally, ketamine can be snorted, smoked (by placing it in either marijuana or tobacco cigarettes), added to beverages, turned into tablets that can be taken orally, or injected.

Ketamine's Many Names

On the street, ketamine is known by many different names, some of which include "Special K," "Super K," and "Kit Kat."

Using any drug without a prescription can be harmful if not dangerous to one's health. Obtaining ketamine illegally can also unknowingly expose users to other drugs as it is often found in combination with MDMA (ecstasy), amphetamines, methamphetamines, and cocaine.

Potential for Ketamine Misuse

The U.S. Department of Justice warns that ketamine is a drug that is often abused for its hallucinogenic effects. Some people even misuse it by giving it to victims that they intend to sexually assault, earning it the reputation of being a date-rape drug.

Since ketamine is a Schedule III controlled substance, it has less potential for abuse than Schedule I and II drugs, but some potential does still exist. Additionally, the abuse of a Schedule III substance can lead to physical and/or psychological dependence.

People with ketamine dependence sometimes experience persisting psychosis similar to that experienced with schizophrenia. This dependence can be created by having taken ketamine for years, along with consuming high amounts of the drug each day.

In addition to developing a ketamine addiction, misuse can also lead to accidental overdose—a situation that can occur due to underestimating the potency of this drug. While death from overdose is rare, misusing the drug can still be harmful to the body and mind.

Ketamine's Adverse Side Effects

Another concern of using ketamine for treatment-resistant depression is that users can experience a variety of negative side effects. One of the most common immediate effects of taking ketamine is feeling strange, weird, or loopy.

Because ketamine can produce feelings of dissociation, people taking higher doses of this drug might also experience what is known as a "k-hole." This is when you feel completely disconnected from your body, such as in an out-of-body experience, and may have limited to no control over your speech and movements.

This drug also has other effects as well. Short-term side effects of ketamine use can include:

  • Cognitive issues related to memory, learning, and attention
  • Confusion or feeling like you're in a dreamlike state
  • Increased blood pressure
  • Muscle stiffness and numbness
  • Nausea
  • Sedation
  • Speech or movement issues, sometimes even becoming immobile
  • Slowed breathing (potentially leading to death)

Long-term consequences of using ketamine include experiencing physical issues such as bladder ulcers and pain, kidney problems, and stomach pain, along with having mental health issues related to depression, experiencing flashbacks, and poor memory.

Factors to Consider Before Using Ketamine for Depression

Ketamine can be effective for treating depression that doesn't respond to standard treatment methods. However, knowing the concerns surrounding ketamine for treatment-resistant depression is only the first step in deciding whether it's the right option for you.

It's also important to consider how you obtain your ketamine. Getting a prescription from your healthcare provider or a mental health professional can help ensure that the drug is safe based on your health status and condition. This is just one area where some ketamine clinics fall short.

Ketamine clinics offer access to this drug in the name of wellness. But research has found that these clinics vary widely, with many not performing comprehensive enough evaluations, inadequately communicating ketamine's effects, and failing to provide the appropriate medical and psychological support during treatment.

For these reasons, it's best to speak with your healthcare team if you are considering ketamine for your depression. Your healthcare provider or mental health therapist can help you decide if it is the best treatment for you based on scientifically-supported evidence and your specific diagnosis and situation.

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Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Kristen Fuller, MD
Kristen Fuller is a physician, a successful clinical mental health writer, and author. She specializes in addiction, substance abuse, and eating disorders.