Ketamine for Surgery Lifts Depression – Too Much is DANGEROUS!

Sometimes patients discover a new use for an old drug on their own. It’s what we call serendipity. The Oxford Reference defines serendipity as: “The occurrence and development of events by chance in a happy or beneficial way.” Vocabulary.com describes the word this way: “If you find good things without looking for them, serendipity — unexpected good luck — has brought them to you.” Japanese researchers discovered over 20 years ago that if they used a low-dose of the anesthetic ketamine for surgery there were surprising benefits for patients with psychological depression. A reader of our syndicated newspaper column discovered this on his own as you will read shortly.

Too much Ketamine Can Be Disastrous:

Perhaps you have heard that Elon Musk is a big fan of ketamine. He was apparently taking it for negative moods. Although the FDA has not approved ketamine for depression, a lot of people are taking it.

My advisor and mentor, Edward Domino, MD, was a professor of neuropharmacology at the University of Michigan. He was the primary author on the first clinical trial of ketamine (Ketalar) as an anesthetic agent (Clinical Pharmacology and Therapeutics, May-June, 1965).

Dr. Domino was excited about ketamine. That’s because this intravenous anesthetic put people to sleep quickly. It had the added bonus of being a powerful analgesic. That meant that it controlled pain really well. If an accident patient was taken to surgery with multiple fractures, ketamine could be beneficial. Ditto for burn patients. Fast anesthesia with powerful analgesia makes it valuable in such situations. The FDA approved ketamine as an injectable anesthetic in 1970.

Dose is Important!

We recently received this message from a reader who received TOO MUCH ketamine during surgery:

Q. We’ve been hearing lately about using ketamine, a thought that scares me to death. Here’s my story: I was on a gurney about to go for a colonoscopy. The tech person could not find a viable vein in my arms for an IV to put me to sleep. The doctor came out and said, “Are you going to get this patient ready or not?” The tech, who was not a doctor, then gave me a shot.

When I woke up later, I could not walk at all. One of the nurses gave my husband a note that said how much ketamine had been given me. My regular doctor later said that was enough to put down a grizzly bear.

At home I barely staggered to the rug in the living room where I laid for about 6 hours, then crawled up the stairs to bed where I stayed for about 12 hours. For three days I was incoherent. My husband thought I had gone into dementia. On the fourth day I was okay again. That’s why I think ketamine is a dangerous drug. It needs careful administration.

A. When administered intravenously by a skilled anesthesiologist, ketamine acts quickly to put people to sleep and provide powerful pain relief.

One of the biggest challenges with this anesthetic is recovery. As patients begin to wake up from anesthesia, they may feel disconnected from their bodies or environment. Some people report distorted perceptions or even hallucinations. It appears that you were overdosed, which led to the prolonged recovery time.

Some people are now using low-dose oral ketamine to manage treatment-resistant depression and post-traumatic stress disorder (Journal of Psychopharmacology, June 5, 2025). The FDA has not approved oral ketamine for any indication.

Depression Lifted Unexpectedly After Ketamine for Surgery:

Q. When I broke my leg a few years ago I needed surgery to reset the bone correctly. The anesthesiologist gave me intravenous ketamine to put me to sleep. As I was recovering from the anesthesia, I experienced an amazing change in my mood, like a cloud lifting from my brain.

I have suffered from depression almost all my life. It is cyclical and has not responded to medication for almost 50 years.

The antidepressant effect of ketamine seemed to last. I have tracked my depression carefully for decades. During my next down cycle, the depression was much reduced.

I started researching this unusual response and discovered that ketamine has been administered off-label for this very purpose. I would like to get another injection of ketamine in the hope that I will continue to get an antidepressant benefit. Is that possible?

A. The ketamine (Ketalar) story is fascinating. This injectable anesthetic has been available for almost 50 years. You discovered by accident an unusual benefit of using ketamine for surgery.

Years ago, Japanese anesthesiologists performed a controlled experiment with ketamine during orthopedic surgery (Anesthesia and Analgesia, July, 2002). They found that this anesthetic helped ease their patients’ depressed mood and suicidal tendencies.

The authors used low-dose ketamine for surgery and found:

“The present study showed that the depressive state of depressed patients administered ketamine improved after surgery. Ketamine is a high-affinity NMDA receptor antagonist. This result is consistent with reports that NMDA antagonists mimic the effects of clinically effective antidepressants.”

“Thus, ketamine has a beneficial effect on the postoperative depressive state and on pain relief for depressed patients who underwent orthopedic surgery.”

The authors summarized their study of low-dose ketamine for surgery:

“In conclusion, small-dose ketamine improved the postoperative depressive state and relieved postoperative pain in depressed patients who underwent orthopedic surgery.”

Other Research on Ketamine:

Since this 2002 research there have been many other studies confirming an antidepressant effect of ketamine. Although anesthesiologists originally used ketamine for surgery, psychiatrists started investigating the drug for hard-to-treat depression.

A review published in the American Journal of Psychiatry (Feb. 1, 2018) analyzed data from 10 controlled studies. The authors were particularly interested in how ketamine worked against suicidal thoughts.

The authors concluded:

“We found that across 10 controlled trials, a single ketamine infusion rapidly reduced the severity of suicidal thinking within 24 hours in more than half the patients, with benefits observed up to one week.

“These results suggest that ketamine holds considerable promise as a potential rapid-acting treatment for patients at risk of suicide. Further research examining ketamine and similar compounds for the treatment of suicidal patients is urgently needed.”

Another analysis of ketamine’s potential applications concluded (European Journal of Pharmacology, July 23, 2019):

“Ketamine’s clinical use began in the 1970s. Physicians benefited from its safety and ability to induce short-term anesthesia and analgesia.

“Recent intensive research brought into light new possible applications of this drug. It began to be used in acute, chronic and cancer pain management. Most interesting reports come from research on the antidepressive and antisuicidal properties of ketamine giving hope for the creation of an effective treatment for major depressive disorder. Other reports highlight the possible use of ketamine in treating addiction, asthma and preventing cancer growth.”

Readers Report Experience with Low-Dose Ketamine

Laura has been on a roller coaster ride:

“IV Ketamine turned my 15 year treatment-resistant-depression (TRD) around in a few hours. I was the first one treated in my area. Establishing dose and frequency was a learning experience for all involved. A maintenance regimen was established, I enjoyed a ten-year remission. I had no side effects and needed no other antidepressants. I regained a life that I never thought was possible. I only wish it was that successful for everyone, but that is not the case.

“Life was good until my doctor retired and the clinic discontinued the treatment. Now I am right back where I was ten years ago. Lack of availability and cost are a huge deterrent to achieving another remission!”

Lori shared this story about her husband:

“My husband has struggled with serious depress for close to 20 years. While conventional antidepressants and psychotherapy allow him to live a relatively normal life, he has encountered periods when these modality are ineffective.

“About 5 years ago when the options were between electroconvulsant therapy or a trial of ketamine compounded locally, my husband and his psychiatrist decided to try ketamine. He has used it as a ‘rescue’ drug since. He has used it 5-6 times throughout those years. He experiences relief for many months before needing another dose. Luckily, he has not encountered any side effects and he has not needed any hospitalizations, ECT, or had any suicide attempts since.”

Not everyone is so fortunate. Some people get no benefit. Others experience side effects. The FDA has approved ketamine for surgery as an anesthetic. The agency has not approved ketamine as an antidepressant.

Esketamine (Spravato) Nasal Spray vs. Depression

The FDA approved a slightly different version of this medication called Spravato (esketamine). It is administered as a nasal spray for “treatment-resistant depression.” The cost can be daunting, though. The retail price could be prohibitive if an insurance company refuses to pay. The out-of-pocket expense might be as much as  $2,000 to $4,000 a month.

Some psychiatrists are using ketamine infusions or nasal sprays off-label to help patients with hard-to-treat depression.

Learn more at this link:

What Should You Know about the Antidepressant Spravato?

Share your own story with either ketamine or esketamine (Spravato) in the comment section. Have you ever had ketamine as an anesthetic. Please tell us how it went.