Summary: A new study shows that ketamine helps people with depression quickly update their beliefs, so they hold fewer negative views. People treated with ketamine become more open to good experiences.
Depression is among the most common mental health disorders. There are dozens of antidepressants for it. But they fail in one-third of cases. This is called treatment-resistant depression (TRD). Ketamine may help in TRD. And it acts fast. Ketamine is still not approved to treat depression. Even so, more and more US clinics now use it for depression, because it often works so well and so fast. So researchers at CNRS, Sorbonne University, and doctors from the AP-HP and the Paris Brain Institute set out to learn how it works in depression. The same questions matter for post-traumatic stress disorder treatment. Ketamine is an approved anesthetic. It may also help manage pain. It is also a popular street drug. But its use as an antidepressant has been rising in recent years. It works best in hard-to-treat cases. Studies show that ketamine increases the ability to overcome negative beliefs leading to severe depression. The results of this study were recently published in the journal JAMA Psychiatry. Depression is among the most common psychiatric conditions. CDC data shows that about 4.7% of US adults live with it. It leads to almost 45,000 suicides each year. People with depression feel sad most of the time. They stop getting joy from life. Many lose interest in life. They often see life in a very dark way and live in constant fear. Negative beliefs are among their biggest problems. In recent years, dozens of new drugs have come out for depression. But drugs do not seem to work in about one-third of cases. These are people with treatment-resistant depression (TRD). So it is vital to find remedies that work for them. Ketamine seems to work in many cases of resistant depression. And ketamine is a well-known drug that has been in clinical use for more than half a century. The amazing thing about ketamine is that it acts fast. Most common antidepressants need weeks to start working. Ketamine starts working within a few hours. To learn how ketamine works in depression, doctors enrolled 26 patients with resistant depression and 30 healthy adults in a study. Researchers asked everyone to guess the odds of 40 bad events happening in their life, like losing a wallet, getting cancer, or having a car accident. Then researchers told them the true odds of those events. The team wanted to see if facts would change people’s beliefs. After hearing the facts, healthy adults updated their beliefs quickly. People with depression had a hard time doing so. After this first test, the team gave the 26 patients with TRD a ketamine infusion three times a week. They repeated the test about four hours after the ketamine. This time, ketamine significantly improved the patients’ ability to update their beliefs. They became less sensitive to bad news, and their mental health improved. Put simply, ketamine made it easier for TRD patients to update their beliefs. The researchers concluded that ketamine significantly improves belief updating in people with TRD. That leads to less depression over time.
Ketamine is also used in chronic pain. Our ketamine therapy page sets out the separate evidence for pain. That evidence does not carry over from the depression research.
Frequently asked questions
How fast does ketamine work for depression?
Within hours. Most common antidepressants need weeks before they start working. In the Paris Brain Institute study, patients with treatment-resistant depression were retested about four hours after a ketamine infusion. Their ability to update negative beliefs had already improved significantly. That speed is the main reason more US clinics now use ketamine for hard cases.
How does ketamine change negative thinking in depression?
It helps people change their beliefs when they get new facts. People in the study guessed their odds of 40 bad events, such as losing a wallet or getting cancer. Then they heard the true odds. Healthy adults adjusted quickly. People with depression struggled to. After ketamine, depressed patients updated their beliefs far better. They became less sensitive to bad news and more open to good experiences.
What is treatment-resistant depression?
It is depression that does not respond to standard antidepressants. Even with dozens of drugs to choose from, they fail in about one-third of people with depression. These patients feel sad most of the time and stop enjoying life. They often hold deeply dark beliefs. Ketamine, a drug in clinical use for more than half a century, works in many of these hard cases.
Is ketamine also used for chronic pain?
Yes. Ketamine is an approved anesthetic, and it also helps manage pain. The evidence for pain is separate from the depression research. So results from depression studies do not automatically apply to pain. Our ketamine therapy page explains how we use it for pain.
Dr. Gurpreet Singh Padda, MD, MBA, MHP
