Efficacy of ketamine for depression

Many individuals have benefited from commonly prescribed antidepressants including selective serotonin reuptake inhibitors (SSRIs). However, these antidepressants often cause a partial or nonexistent effect. What are the options in such circumstances? Recent studies are showing that certain type of ketamine might be of assistance.

In a 2006 National Institute of Mental Health study, 18 treatment-resistant patients with severe depression showed significant reductions in depression scores within hours of a single dose of ketamine — an unusually fast response compared to antidepressants, which typically require weeks. Research suggests that ketamine promotes rapid synaptogenesis (the formation of new synaptic connections) through a cascade involving NMDA receptor antagonism, a glutamate surge, AMPA receptor activation, and increased BDNF and mTOR signaling. This may help reverse the synaptic deficits associated with chronic stress and depression.

The Food and Drug Administration (FDA) approved the first brand-new major depression drug on March 5, 2019. The medication is an esketamine nasal spray produced from ketamine, a controversial anesthetic known for its unexpected antidepressant properties.

What is ketamine therapy and how is it used to treat depression?

In the 1960s, ketamine was developed as a dissociative anesthetic in Belgium. In 1970, the FDA approved it for human use, and it has been widely used in human medicine ever since: in emergency rooms, operating rooms, and battlefield medicine. During the Vietnam War, it was used for the treatment of wounded soldiers on the battlefield.

Emergency personnel may administer it to a patient whom they have saved from a suicide attempt, for instance. According to some physicians that first became aware of the medication’s possible benefits and its potent antidepressant effect.

Ketamine produces what medical professionals refer to as “dissociative effects” but what most people would refer to as “trips.” That is how it developed into a club drug that goes by the names like Super K and Vitamin K among others. It is injected, ingested, snorted, or added to cigarettes.

If you’re weighing all your options for treatment-resistant depression, our psilocybin therapy for depression article covers the Phase 3 trial evidence and what’s currently accessible in Europe.

The drug ketamine, which was and still is frequently used as an anesthetic during surgeries turned into a nasal spray called esketamine. Which is interestingly shown to be involved with glutamate production. One of the most prevalent neurotransmitters in the brain, glutamate controls a significant portion of the neurological system. Dysregulated glutamate signaling has been implicated in depression. Ketamine works by blocking NMDA-type glutamate receptors, which paradoxically triggers a surge of glutamate that activates AMPA receptors, leading to increased BDNF release and rapid synaptogenesis.

This process may help the brain become more adaptive and capable of forming new neural connections, potentially giving patients a window to develop healthier thought patterns and behaviors. Traditional antidepressants (SSRIs/SNRIs) also promote neuroplasticity over time, but ketamine’s mechanism is distinct and notably faster-acting.

Ketamine treatment types

Intravenous ketamine infusions (IV): Ketamine Infusions for treatment-resistant depression are inserted into your circulation by a steady, continuous IV drip. Only an authorized doctor in a medical facility or clinic atmosphere is appropriate for this.

Shots administered intramuscularly (IM): In a clinic or hospital environment, shots are administered into a major muscle, like your thigh or arm.

Sublingual tablets: This version of ketamine is given for at-home usage as a stand-alone medication or maintenance in between IV or IM sessions. A tablet is placed beneath the tongue, where it slowly dissolves. This kind of ketamine is thought to be less powerful than other types since it takes more time for your body to process it.

Nasal spray: Because someone will need to watch for potential side effects, Sprovato (esketamine) can only be given at a hospital or doctor’s office. For the first eight weeks, you’ll apply the spray once or twice a week.

The research on ketamine treatment

Esketamine (Spravato), a prescription form of ketamine that is administered through a nasal spray, was approved by the FDA in 2019. However, the rules of the research state that it can only be used “under the guidance of a healthcare professional in a qualified doctor’s office or clinic.”

Medical professionals must keep an eye on your vital signs and the course of your condition after a dose. In a trial where ketamine (together with the standard oral antidepressant) helped patients stay in stable remission 16 weeks into treatment, it was discovered that nasal ketamine has rapid action and longer-term efficacy.

Is ketamine treatment right for you?

Your psychiatrist or prescribing physician can assess whether ketamine is appropriate given your treatment history, current medications, and cardiovascular health.

Keep in mind that ketamine is not a first-line treatment for depression, anxiety symptoms, mood disorders, or other mental health conditions and is typically only used when other, more established treatments, have failed. It is believed to just temporarily improve depressive symptoms rather than constitute a cure. Using the side effects as a guide, it is simpler to determine who should not receive ketamine.

Other uses of ketamine

Researchers discovered that single-dose of ketamine IV decreased depression scores, panic, irritation, and other anxiety symptoms in individuals with a generalized anxiety disorder (GAD) and social anxiety disorder in another analysis published in 2022. Ketamine was more beneficial in larger doses than in a lower dose, and the effects could linger for up to two weeks.

According to a small 2017 study, one hour after receiving a subcutaneous (under the skin) dose of ketamine injections, 83% of participants with GAD and social anxiety disorder reported fewer anxiety symptoms. And a few additional studies showed that ketamine may be useful in treating particular phobias.

For instance, a small 2021 study found that participants’ evaluations of agoraphobia (the fear of specific locations or circumstances from which one would be unable to escape) decreased after receiving subcutaneous (under the skin) ketamine injections.

Anxiety disorders like OCD are characterized by uncontrollable and compulsive thoughts and actions. A 2013’s brief study with 15 OCD patients who had practically continual obsessive thoughts was a part of the research. Two IV infusions were given to them, spaced at least a week apart. One injection was a placebo that just contained saline. The other had ketamine in it. In contrast to participants who got a placebo infusion, those who received ketamine after the infusion reported a considerable improvement in their ability to control obsessive thoughts. For several subjects, the effects of the ketamine infusion lingered for more than a week.

What are the adverse effects of ketamine?

Continuous use of ketamine has side effects. It can lead to unconsciousness, high blood pressure, and severely slowed breathing. The medication may also result in long-term issues like poor memory, kidney difficulties, stomach pain, ulcers, and bladder pain. If you use ketamine while intoxicated or if you overuse alcohol, it could be lethal.

However, the drug’s potential to alleviate depression and act as a preventative against suicidal thoughts has caught the attention of academics. In controlled, clinical settings, it has been researched and used to treat diseases like unipolar depression that are resistant to treatment, among others.

Unrestricted use is not a form of treatment for depression, to be clear. However, doctors have created a protocol for use under medical supervision that could benefit patients who don’t respond to antidepressants.

Ketamine can be addictive. Since the drug’s effects on the mental state are so strong, once an addiction takes hold and a person uses it frequently, it can be simple to identify.

How safe are ketamine clinics?

Ketamine outpatient clinics run independently are springing up everywhere. These clinics are thought to number in the hundreds to thousands at present, practically all of which were started when ketamine was licensed. The clinics are typically businesses with a staff that includes a psychiatrist with certificate for psychedelic-assisted therapy, a nurse or an anesthesiologist -who can administer the infusion.

These ketamine clinics present some concerns, such as what to look for in a reliable clinic. We don’t currently have clear responses to that question. Ketamine infusions, which can result in a deep dissociation from reality, raise the question of whether they would be better managed in a hospital setting, where there are established procedures for safety in the event of an emergency.

Certificate programs

The Certificate programs for Psychedelic-Assisted Therapies are created largely to satisfy the expected need for qualified therapists to deliver research and regulatory-approved psychedelic-assisted therapy sessions.

A word about depression

Major depressive disorder or depression, is a severe medical condition that affects people’s feelings, thoughts, and behaviors. Sadness or a significant decrease in interest in previous hobbies are symptoms of depression. It can impair your ability to perform at work, and it can cause several mental and physical issues. From moderate to severe, depression might include:

• Experiencing sadness
• Loss of interest in once-enjoyed activities
• Changes in appetite, weight loss, or gain unrelated to diets
• Inability to sleep or excessive sleeping
• Energy loss or increased fatigue
• A sense of worthlessness or guilt
• Having trouble focusing, thinking, or making decisions
• Suicidal ideation

Depression must be diagnosed if the symptoms last for two weeks. It’s important to rule out certain general medical ailments because conditions like thyroid problems, neurological disorders, and nutrient deficiencies can mimic the signs of depression. One in 15 adults (6.7%) is thought to experience depression each year. In addition, 16.6% of the population will experience depression at some point in their lives. Although it can strike at any moment, depression typically first manifests itself in late adolescence to mid-life. Depression is more common in women.

Could ketamine provide hope for people with treatment-resistant depression?

People with severe, treatment-resistant depression may lose hope in their future and in their ability to ever feel better. Ketamine may provide rapid symptom relief for individuals who have not responded to multiple antidepressant trials. Several studies have found that ketamine produces rapid reductions in suicidal ideation — in some trials within hours of a single infusion, which has prompted researchers to investigate it specifically as an acute anti-suicidal intervention.

The key open questions now are how to sustain ketamine’s effects beyond the initial response period, which patients are most likely to benefit from repeated infusions, and how to standardize protocols across the rapidly growing network of outpatient ketamine clinics.