Ketamine for Depression

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Medically reviewed: Paloma Lehfeldt, MD
A couple discussing ketamine for depression

Ketamine Treatment for Depression Could Be the Breakthrough of the Century

Depression affects millions of Americans every year. For many, depression symptoms can make life difficult or unbearable, especially for those diagnosed with treatment-resistant depression (TRD) or major depressive disorder (MDD). Treatment-resistant depression means you have responded poorly to at least two treatment modalities. 

If you or a loved one are living with depression and have tried multiple treatments to no avail, things may seem desperate. However, recent research on the dissociative anesthetic ketamine may provide a ray of hope.

Since the early 2000s, researchers and medical professionals have been looking into using ketamine to treat depression, often with resounding success. One study suggests that ketamine for depression may help up to 70% of patients with treatment-resistant depression experience rapid symptom relief, sometimes just a few hours after treatment. Although more research is needed, the results are promising.(1)

While everyone’s situation is different, and you should always consult a medical professional before starting a new treatment plan, ketamine could be a potent alternative treatment for depression.

Everything You Need to Know About Ketamine Therapy for Depression

Ketamine is an anesthetic medication used for nearly five decades. Initially approved as veterinary medicine, ketamine saw its first human use in the 1970s as a battlefield anesthetic. Since then, it has become one of the most prevalent medications for pediatric, elder care, and surgical applications where patients may be at risk for respiratory complications. This is due to ketamine’s non-depressive (meaning it does not interfere with) effect on a patient’s breathing ability. 

Beginning on February 15th, 2000, ketamine saw its inaugural trial as an off-label (used for a condition other than what it is FDA approved for) treatment for depression. After its initial successful uses, researchers and medical professionals began exploring ketamine’s potential for addressing various mental health conditions, including anxiety, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and even pain management and chronic pain.
Progressive ketamine research culminated with the FDA approving the first ketamine derivative for the treatment of depression. Spravato, also known as esketamine, is a type of ketamine administered via nasal spray that treats depression and suicidal ideation. Medical professionals often pair ketamine with licensed psychotherapy. This is known as ketamine-assisted psychotherapy (KAP). 

What is Depression? 

Depression, major depressive disorder, and treatment-resistant depression are significant illnesses that affect millions of people around the world. In the United States alone, over 21 million adults are diagnosed with depression yearly.(2)

Depression can be incredibly debilitating for some individuals and may interfere with their ability to maintain their usual activities and commitments. For instance, major depressive disorder may accompany severe anxiety, suicidal ideation, and withdrawal from everyday life. Some additional forms of depression can also be deeply painful and disruptive to daily life. Treatment-resistant depression is a type of depressive condition in which patients do not respond to two or more treatment modalities, such as selective serotonin reuptake inhibitors (SSRIs) and psychiatric intervention.(3)

The CDC estimates that around 30% of people with depression will not respond to typical treatments. However, ketamine therapy and esketamine are quickly gaining traction as alternative treatments for depression.(3

What Are the Most Common Depression Symptoms?Depressive conditions carry many different symptoms. Some, such as a lack of appetite, or loss of interest in hobbies and relationships, can significantly affect a person’s social life and personal relationships. Others include:(4)

  • Sadness
  • Irritability
  • Frustration
  • Emptiness
  • Guilt
  • Decreased Energy
  • Constant Fatigue
  • Cognition Difficulties
  • Physical Pain
  • Headaches
  • Self-Harm
  • Suicidal Ideation

What Causes Depression?Depression is a highly complex condition that is not fully understood. Research suggests there is much more to depression than a chemical imbalance in the brain. What is known is that depression can have a host of triggers ranging from chemical imbalances in the brain, stressful events, upheavals in your personal or work life, trauma, and illness, to substance abuse.(4)

ketamine for mental health

What is Treatment-Resistant Depression?The most common pharmaceutical treatment for depression is prescription medications such as selective serotonin reuptake inhibitors. SSRIs affect the body’s serotonin system. Serotonin is a neurotransmitter partially responsible for regulating mood. However, up to 30% of people with depression will not respond to antidepressants, the majority of which are SSRIs. A small portion of the population may experience suicidal ideation and self-harm while taking an SSRI.(5)

These patients likely have what is known as treatment-resistant depression, which is a failure to respond to two or more treatment modalities. If you have TRD, you may feel you’ve run out of options. Thankfully, ketamine therapy may be the right therapy for your depressive condition.(5)

What is Ketamine Therapy for Depression?Clinical trials and research show that ketamine holds significant potential as a treatment for depression. Some forms of ketamine, such as esketamine, have received FDA approval for treatment-resistant depression and depressive symptoms in adults with major depressive disorder. Spravato is also approved to treat patients with acute suicidality when paired with an antidepressant. However, ketamine is also used off-label to treat depression. Off-label means a medical professional has prescribed a drug to treat conditions outside its original FDA-approved usage. 

How Does Ketamine Work for Depression?Ketamine treats depression by acting on the brain’s glutamate system. As an N-methyl-D-aspartate antagonist, ketamine modulates the actions of glutamate in the brain. Glutamate is an important mood-regulation neurotransmitter believed to significantly impact depression symptoms.(6)

By modulating glutamate, ketamine may impact depressive symptoms. However, the exact mechanism is still debated by medical professionals and healthcare providers. Some patients report experiencing rapid symptom relief within as little as 24 hours post-treatment, although not all patients will have the same results.(7)

Ketamine Infusion Therapy for Depression

Recent double-blind, placebo-controlled (a study where neither the researchers nor participants know which group is the control) studies showed that ketamine could be a potent antidepressant. Researchers enlisted ten healthy volunteers suffering from treatment-resistant depression. The participants underwent six one-hour ketamine infusion sessions over six weeks.(8)

The research team observed significant reductions in depression symptoms in the first-hour post-infusion vs. the participant’s baseline scores. Most patients experience beneficial effects within 24 hours. These patients showed a 70% response rate to the medication.(8)

Another potential benefit may come from ketamine’s dissociative effects. Dissociative medicine can cause you to feel like you’re detached from your body and even, in a therapeutic setting, past trauma. Many patients report that this gives them a top-down view of their condition and what may be triggering it.(9)

This change of perspective allows them to discuss sensitive issues with their healthcare provider. Often in a way that lacks the usual fear response or embarrassment. This potential increase in objectivity may allow patients to heal faster and more fully.

While further research into ketamine’s potential needs to be done, many professionals are enthused by the results. Initial findings are promising. Hundreds of providers across the country have been using ketamine infusion therapy to help their patients experience a greater quality of life. 

a woman undergoing ketamine infusion therapy to help treat depression

What are the Risks of Ketamine?Ketamine is a relatively safe and well-tolerated drug with over five decades of medical usage. However, ketamine has some risks, particularly for people with schizophrenia and high blood pressure.(10)

Some ketamine side effects during treatment (one to two hours) may include:(10)

  • Confusion
  • Nausea
  • Dizziness
  • Minor Headache
  • Stomach Cramps
  • Muscle Stiffness
  • Increased Body Load (feeling heavy)

Could Ketamine Help Manage Your Depression?Ketamine won’t be for everyone, but it could be right for you. Ketamine-assisted psychotherapy may be a good option if you have failed to respond to multiple treatment types or suffer from chronic depression or major depressive disorder. Before starting a new therapy plan, you should consult a medical professional or health care provider. Ketamine therapy, in particular, usually requires a diagnosis. Find ketamine treatments near you to schedule your consultation.

Where to Find
Ketamine TreatmentLocate outpatient ketamine clinics and at-home ketamine service providers in the U.S. that offer care for pain, depression, anxiety, PTSD, OCD, and addiction.