Ketamine in the treatment of depression: what you need to know

Jeff Vinograd suffered from depression throughout his adult life. Since the age of 20, he has been taking various antidepressants that were available. But the depression did not go away.

At 45, he already had two young children and was working as a film and video producer in Portland, Oregon. But he still could not overcome this illness. Depression simply paralyzed him.

As Jeff says, he sat on the couch all day, unable to move his arms or legs. He had already started thinking about suicide, but he was worried about how he could do it without traumatizing his children.

Around the same time, a friend of his who worked as a doctor advised him to take ketamine for depression.

What is ketamine?

This drug first appeared in Belgium in the 60s and was used as an anesthetic for animals. In 1970, the FDA approved ketamine as an anesthetic for humans. It was used during the Vietnam War to treat wounded soldiers.

Since the early 60s, ketamine has gone through a great evolutionary journey from an anesthetic to a party drug and antidepressant. So, what is ketamine therapy and how can it help fight depression without causing side effects?

For example, rescuers use ketamine as a sedative for a person they rescued from a suicide attempt. Dr. Ken Stewart says that this drug is a powerful antidepressant and also helps to get rid of suicidal thoughts. Many doctors have noticed this effect.

When a man tries to jump off a bridge and emergency doctors give him ketamine as a sedative, 9 months later he says that he hasn't thought about suicide at all all this time.

The more stories like this emerge, the more doctors are convinced that there is something special about this drug, says Dr. Stewart, who works as an emergency room physician and is the founder of Insight Ketamine in Santa Fe, New Mexico. Stewart, like ketamine itself, began his medical career during the Vietnam War. Today, ketamine therapy is widely used to treat people who are suicidal.

This drug causes a state that experts have called “dissociative experience” or “trip”. That's why ketamine once became a club drug called K, Special K, Super K, and Vitamin K. It is used for injections, added to various drinks, snorted, and added to tobacco or marijuana.

According to John Crystal, MD, head of the Department of Psychiatry at Yale-New Haven Hospital and Yale School of Medicine in Connecticut, where he is closely involved in the study of the antidepressant effect of ketamine, this drug can cause people to feel that what is happening is unreal, which manifests itself in visual and sensory distortions, distorted perception of their own body, temporary non-standard thoughts and beliefs, as well as feelings of euphoria and high.

The drug lasts for about 2 hours, but since there are great risks associated with taking ketamine, it should be taken only as prescribed by a doctor and under his/her supervision. If you do not follow the recommendations of a specialist, it can lead to loss of consciousness, high blood pressure, and slowed breathing, which is very dangerous for human life. In addition, the drug can cause long-term problems, including

• pain and ulcers in the bladder
  
• kidney dysfunction;
  
• stomach pain
  
• depression;
  
• poor memory.
  

In combination with alcohol, ketamine can be fatal to humans. It should be noted that ketamine depression is one of the serious side effects of uncontrolled drug use.

At the same time, ketamine depression treatment has great potential, so experts have paid close attention to it. They studied its effects and used it in clinical settings under full control.

It should be remembered that daily ketamine intake is not a way to treat depression. Doctors have developed a special protocol that provides for the use of the drug under the full supervision of a doctor if other medications do not help the patient.

How to take ketamine

The FDA warns that ketamine and its derivatives are not approved by the organization for the treatment of any mental disorders. This means that the safety and effectiveness of this drug has not yet been fully proven.

Also, in 2019, the FDA approved the use of esketamine nasal spray (Spravato), a ketamine derivative used to treat resistant depression, but only in a certain category of patients who take antidepressants orally and under strict supervision of a specialist in certified clinics. The spray can be an alternative option for patients who have not been successful with antidepressants, as well as for people with serious depressive disorders and suicidal tendencies. In this case, they take antidepressants and also receive esketamine under the supervision of a certified specialist or in a hospital, where the person is monitored for 2 hours after taking the drug.

Therapeutically resistant depression involves treatment with the spray in the following order

1. 1 to 4 weeks (patients receive the drug twice a week).
   
2. 5 to 9 weeks (the drug is used once a week).
   
3. 1 to 2 weeks (once a week).
   

The spray bottle has a black boxed warning about the risk of sedation and problems with concentration, judgment, and thinking, as well as the risk of overuse or misuse of the drug and suicidal thoughts.

Other forms of ketamine that have been approved by the FDA for the treatment of psychiatric disorders include intravenous injections. Most of the research is focused on intravenous use of the drug, which is done only under medical supervision.

Dr. Stewart sees patients in his clinic who have a referral from a specialist who has diagnosed treatment-resistant depression. The doctor does not make diagnoses himself. Treatment begins with 6 infusions with a 3-week break, which have been confirmed by relevant studies.

This is how treatment begins, says Dr. Crystal. At first, intravenous injections are given 2 times a week, then once a week, and finally once every 2-4 weeks.

Most studies stop the initial treatment at week 6, as there is no evidence that longer therapy will bring more benefit. At the same time, some people return to re-treatment when their depression symptoms return.

The IV infusion is designed to last 40 minutes. Dissociative experience occurs quite quickly and passes in 15-20 minutes after the procedure. Therapy takes place only under the supervision of a doctor. He or she does not always sit next to the patient, but is within easy reach if any problems arise.

Under the drip, patients mostly look asleep, says Dr. Stewart, as most of them lie still and don't talk. But some may speak or describe the music playing in their headphones, talk about their experiences, or ask where they are. No one interferes in the therapy process unless necessary.

Krista Coulter-Scott, a pediatric nurse from Athens, Georgia, was treated at a similar clinic in Gainesville. She reports that she did not want to wake up because she was on a spiritual journey. She was enveloped in a sense of warmth, safety, and confidence. As the treatment continued, all the stress was lifted from me in layers, the nurse says. I felt all the power and strength of the universe.

This statement was made by a fifty-year-old woman who had been depressed and anxious since early childhood. Later, she was diagnosed with PTSD and chronic pain. She also took more than ten different antidepressants over the years of her illness, but they did not help her overcome her depression.

Only ketamine therapy was able to cope with the problem. The woman reports that her head is lighter, her gloomy, dark and heavy feelings have disappeared, and everything around her has become much brighter and lighter.

When Krista returned to work after the ketamine drip, she asked a colleague if the lighting in her office had changed. But it remained the same. She still can't figure out if this is a side effect of the drug or a side effect of the depression reduction.

Jeff Vinograd talks about this effect as well, describing the feeling of floating in color. “I had the feeling that I was in a 'happy place'. It was a space where everything related to real life simply disappeared, and I had none of the negative burden that I had to carry with me all the time,” says Vinograd.

The antidepressant effect of ketamine can wear off in a few hours, days, or weeks after the first drip. Longer-term therapy has a longer-lasting effect.

Ketamine can be effective for severe forms of depression and anxiety, but there are also alternative methods for managing anxiety. Depending on the type of anxiety, different solutions may be recommended, which we discuss in detail in our article "How to deal with relationship anxiety".

Returning to reality

In Dr. Stewart's clinic, after stopping the mind-altering treatment of depression with ketamine, the doctor comes to the patient and talks to him, integrating him into real life. This kind of talk therapy can be done in other clinics with other specialists.

This is very important, Stewart says, because when patients come out of this deep experience, they have something to share with the world around them, as they have a lot of knowledge and have had many experiences throughout their lives. In most cases, ketamine is the reason for unpacking this baggage.

Christa, who now works at the Connecticut Veterans Affairs Healthcare System and Yale University Hospital in New Haven and provides intravenous infusions and intranasal injections of the drug for treatment-resistant depression, recommends that patients do not stop psychotherapy after completing ketamine treatment.

Also, doctors who prescribe ketamine intravenously advise patients not to stop taking antidepressants that were prescribed earlier. As for the nasal spray, it is used only in conjunction with oral antidepressants and only in certified clinics.

The doctor says that ketamine is an intervention, but the concept of “treatment” has a much broader meaning.

A few weeks, months, and even years after the first therapy of 6-8 doses, people can return for a second course of treatment. There are no general recommendations on the need for revaccination, so it is carried out as prescribed by a doctor if the symptoms of depression have resumed.

About 30% of people no longer need therapy after the first series of injections. For those who repeatedly come for therapy, such series become more and more distant from each other and eventually they stop altogether.

How ketamine therapy works

The effect of the drug for Winograd and Coulter-Scott continues after the first therapy. Experts are studying why this happens.

To date, they have found that some patients suffering from depression do not experience the feeling of drug intoxication caused by ketamine. However, the drug significantly alleviates the course of depression and begins to work within a few days after the first drip session.

When ketamine enters the body, a person experiences dissociative effects that are not related to treatment, says Crystal. It's just something you have to go through to get the treatment you need. Ketamine therapy is the brain's response to the drug, that is, how it reacts to its presence in the body.

The brain's response can be different depending on the condition a person is in. In some people with prolonged depression, some neural connections in the brain, called synapses, are lost, which facilitate communication between nerve cells.

“We think that the number of synapses decreases because depression is such a stressful situation that a person actually cuts or loses important synaptic connections in the cerebral cortex,” says Crystal.

But studies show that within a day of taking the first dose of ketamine under medical supervision, the lost cell connections begin to be restored. And the more synapses a person has, the higher the antidepressant effect of the drug.

Other effects of the brain

There are other effects that ketamine has on the human brain. Some brain cells (neurons) that are responsible for mood use a neurotransmitter, a chemical (glutamate), to communicate with each other. Such neurons need glutamate receptors to join this communication.

In patients with depression, such nerve cells are no longer able to be excited by glutamate, as if its receptors have been deactivated or weakened.

But after ketamine administration, these neural connections begin to be replenished with new glutamate receptors. This action is similar to the way ketamine helps create new networks to catch glutamate so that neurons can respond to it again.

Studies show that despite the fact that the main action of the drug is aimed at restoring glutamate receptors, it also needs opioid receptors for an antidepressant effect. Psychiatrist Alan Schatzberg, M.D., who conducted a number of studies and discovered this fact, is concerned about this.

He says it may not be a big deal, but he is concerned that the drug works through an opioid mechanism. Other researchers have also noticed that over time, patients may need more and more doses of ketamine to feel its effects and experience relief, just as with painkilling opiates. The correct dosage and its gradual reduction will help reduce this risk.

Of course, any comparison with opiates leads to the question of addiction. Excessive use and improper dosage can lead to negative consequences, as warned by the “black frame” on the esketamine can.

Shatzberg, director of the Center for Mood Disorders at Stanford University, says that ketamine is less addictive than opiates, but its use is not without risks. In fact, some cases have been described in which people have shown signs of addiction with prolonged use of the drug or excessive use.

It is not yet entirely clear whether the risk of dependence or tolerance outweighs all the benefits. It should be noted that for some people who have been taking psychotropic substances for a long time, the use of ketamine can be dangerous. Clinical trials did not involve people who had problems with psychotropic drugs.

Ketamine can also be dangerous for patients with schizophrenia, as it can temporarily worsen the symptoms of psychosis.

Changes in the brain

When it comes to the effect of ketamine on glutamate receptors, the process of synapse repair and reactivation will help the brain change and get out of prolonged depression. It will also help to understand why taking antidepressants or psychotherapy did not affect actions before using ketamine and why it helped afterwards.

Vinograd says that he resorted to psychotherapy before using ketamine only at the request of his family. But after he started feeling better, his doctor began to understand him better.

Crystal reports an improvement in sleep quality. Insomnia is a common symptom of depression. She is raising her granddaughter alone and says that she is still stressed, but it is not accompanied by anxiety and dark thoughts that she used to have.

Treatment costs and health insurance

Basically, the only ketamine-based drug used to treat depression that is covered by health insurance is the nasal spray esketamine, because it has been approved by the FDA organization.

Since the FDA has not approved the use of the drug by drip, most insurances do not cover it. The cost of the infusion can vary and is usually purchased by the patient at their own expense. A full course of treatment can cost several thousand dollars.

According to Crystal, some patients and their doctors prefer the drop method of ketamine administration to the nasal method. But today there is no conclusive evidence on which is better.

Some patients are unable to continue treatment due to lack of money or health insurance that covers such costs. Stewart says he doesn't know why some people don't return for continued therapy. Perhaps they have started to feel better, or perhaps they simply do not have the money to buy the drug.

For example, Vinograd's insurance did not allow him to get revaccinated, even with a nasal spray, despite the fact that doctors consider it necessary. In the meantime, he reports that the great relief that the first series of treatments brought him is still in effect.

This is not a temporary change, Stuart says, but a shift that has shown me myself and how I relate to the world, my own emotions and feelings.

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