Ketamine may be helpful for some people who have treatment-resistant depression.
In 2020, approximately 21 million adults (aged 18 and older) had a major depressive episode in the past year. Depression is a serious mental illness that impacts a large percentage of the population, but only about 66 percent of people get the treatment they need.
Nearly 9 million people in the United States are medically treated for major depressive disorder (MDD), but close to a third have treatment-resistant depression (TRD) that does not respond to traditional treatment. This is where ketamine therapy for depression comes in.
What Is Ketamine Therapy?
Ketamine is a short-acting anesthetic drug with dissociative and hallucinogenic properties. It has been shown to also be effective in treating depression that does not respond to traditional therapies, reducing suicidal ideations by up to 50 percent, and lowering generalized anxiety symptoms by 30 percent.
Ketamine therapy is becoming more common for treating treatment-resistant depression after other medications and treatment methods have proven ineffective.
Ketamine therapy involves administering the medication in a supervised professional treatment environment where a medical or mental health professional can monitor your reactions. Ketamine works as a fast-acting antidepressant. Typically, during ketamine therapy, you will continue to take your antidepressant medications and attend therapy and counseling sessions as well.
Ketamine stimulates a different part of your brain than traditional antidepressant medications. During ketamine therapy, you will remain on site in a specialized clinic for about two hours.
After the therapy, you can feel sleepy, and you should have someone else drive you home. The next day you can wake up feeling refreshed and notice an improvement in your mood.
Key Facts About Ketamine Therapy
- Ketamine can provide fast relief of depressive symptoms, often as quickly as within 40 minutes as opposed to antidepressant medications that can take weeks to take effect.
- One study showed that nasal ketamine, when taken in conjunction with regular antidepressants, maintained stable remission for 16 weeks.
- Ketamine acts quickly to improve symptoms of depression. Studies show sustained improvement for up to a month after the last dose.
- Ketamine for depression is available in two forms: “R” and “S” ketamine, which are ketamine infusions and nasal spray respectively.
Ketamine’s Effect on Depression
Ketamine is best used to treat depression that is not responding to other forms of treatment. It is not generally used as a first-line treatment option.
Ketamine is FDA-approved as an anesthetic medication. As of March 2019, it is approved as a nasal spray (Spravato) for treatment-resistant depression.
When used to treat depression, it is given in a much lower dose than is needed for sedation. It can provide a kind of “timeout” for the brain, as it works differently than traditional antidepressant medications.
Ketamine has been proven to reduce thoughts of suicide and suicidal ideations, as well as improve moods and successfully manage depressive symptoms.
Ketamine is a dissociative drug that can change your sensory awareness while undergoing ketamine therapy. It can make colors seem brighter and give you a feeling of floating or being outside of your body, for instance.
Ketamine therapy can offer a peaceful and beautiful experience that can help to reset your brain’s emotional pathways. This can make you more open to positive feelings, making therapy more effective. Ketamine therapy for depression can very quickly improve your moods and ways of thinking, and these positive changes can last for a period of time.
What Are the Benefits of Using Ketamine Therapy for Depression?
Ketamine therapy can help to improve depressive symptoms in up to 70 percent of cases, and the effects can be long-lasting. Ketamine works quickly in the brain to improve symptoms, and these positive effects can continue for up to a month or longer.
Treatment-resistant depression can be debilitating, and it may include suicidal ideations. In 2020, there were 1.20 million suicide attempts and over 45,000 deaths by suicide in the United States.
Ketamine therapy can help to reduce rates of suicide by improving mood and minimizing thoughts of suicide. It can also be effective in treating anxiety symptoms that are concurrent with treatment-resistant depression.
How Does Ketamine Therapy for Depression Work?
It is not clear exactly how ketamine works to manage depression. However, it is known that ketamine interacts with NMDA receptors in the brain, blocking them, which in turn increases levels of glutamate, an excitatory neurotransmitter. This can help to stimulate nerve cell action, which can dispel some of the symptoms of depression and improve moods.
Ketamine can also enhance the neuroplasticity of the brain and create new neural connections, which can have an effect on some of the brain’s wiring of the reward processing pathways. This can then mitigate some of the negative side effects and thought processes of depression.
It can also allow the brain to be more flexible, opening up new feelings and making a person more adaptable and open to therapy methods. The brain’s chemical makeup and wiring are often negatively impacted by depression or due to depression, and this can be improved with a different sort of drug like ketamine.
What Are the Different Types of Ketamine Therapy?
There are two main types of ketamine therapy: ketamine infusions involving racemic ketamine (R,S ketamine) and ketamine nasal spray using esketamine (S-ketamine). Ketamine lozenges and dissolvable tablets are also available, but these are less common and not as well researched.
Ketamine Infusions (IV)
The racemic version of ketamine, R,S ketamine is given through an IV infusion at a specialized clinic. You will typically sit in a comfortable chair and listen to music for about 40 minutes while the infusion completes. Intramuscular injections of ketamine are also available.
The number of treatment sessions can vary, but it is typically recommended to have six treatments over two to three weeks initially. Therapy sessions are also often included once the effects of ketamine dissipate.
IV ketamine is not FDA-approved to treat depression, and it is therefore being used off-label during ketamine infusions or injections. Since ketamine infusions for depression are not FDA-approved, they will not be covered by insurance.
Racemic ketamine is 100 percent bioavailable, meaning that the entire dose is available to be used by the brain, which can make it more effective. When getting ketamine infusions, you will also need someone to drive you home after the session.
Ketamine Nasal Spray
S-ketamine, or esketamine, is FDA-approved for treatment-resistant depression under the brand name Spravato when administered in a clinical setting under the supervision of a health care provider. It is commonly covered by insurance for eligible individuals for whom other types of depression treatments are not working.
Ketamine nasal spray is usually given twice a week for the first month. Then, it’s given once a week for the next month.
S-ketamine is a more potent psychoactive drug that can have more dissociative side effects, which can lead to more feelings of detachment from the body and sense of self. Due to the nature of the potential side effects, you will need to be observed for about two hours after taking Spravato.
The nasal spray version of ketamine is less bioavailable than the infusions. Because of this, it may be less effective for some people. However, it can also be effective in relieving depressive symptoms for longer when taken in conjunction with an oral antidepressant.
What Are the Risks & Side Effects of Ketamine Therapy?
Ketamine can have some side effects. The most common include the following:
- Heightened blood pressure
- Blurred vision
- Perceptual disturbances
In some cases, ketamine therapy can cause agitation, negative feelings, sensory and perception distortions, and an unpleasant and scary “out of body” experience. It is important that ketamine therapy be closely monitored during the session and for a period of time following it to ensure patient safety.
Ketamine therapy is not recommended for people with a history of psychosis, as it can make these symptoms worse. It also is a drug of abuse and has some potential for dependence and addiction potential. Therefore, it should be avoided by people with a history of drug abuse or addiction.
Will I Get Addicted to Ketamine Therapy?
Ketamine therapy is administered in specialized clinics or medical settings under the direction and supervision of a trained professional. As such, the medication is less likely to be misused, and doses can be altered to avoid complications or side effects.
Still, ketamine does have addictive properties, and it is possible to develop dependence on and addiction to ketamine. You are much more likely to develop these issues when misusing ketamine than when taking it as directed through a structured ketamine therapy program.
If you have a history of drug abuse or addiction, ketamine therapy is likely not the optimal treatment option for you. Ketamine use can cause euphoria, or a “high,” that can then trigger a potential relapse.
Again, ketamine therapy should only be used as directed while monitored by a trained health care professional.
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- Clinical Effectiveness of Intravenous Racemic Ketamine Infusions in a Large Community Sample of Patients with Treatment-Resistant Depression, Suicidal Ideation, and Generalized Anxiety Symptoms: A Retrospective Chart Review. (September 2022). The Journal of Clinical Psychiatry.
- Ketamine for Treatment-Resistant Depression: When and Where Is It Safe? (August 2022). Harvard Health.
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients with Treatment-Resistant Depression: A Randomized Clinical Trial. (September 2019). JAMA Psychiatry.
- Efficacy of Ketamine Therapy in the Treatment of Depression. (September–October 2019). Indian Journal of Psychiatry.
- FDA Approves New Nasal Spray Medication for Treatment-Resistant Depression; Available Only at a Certified Doctor’s Office or Clinic. (March 2019). U.S. Food and Drug Administration.
- Suicide Statistics. (2022). American Foundation for Suicide Prevention.
- Ketamine for Depression: What it Feels Like and Who it Can Help. (September 2022). The Washington Post.
- Ketamine and Depression: A Narrative Review. (August 2019). Drug Design, Development and Therapy.
- Repurposing Ketamine in Depression and Related Disorders: Can This Enigmatic Drug Achieve Success? (April 2021). Frontiers in Neuroscience.