The People's Perspective on Medicine

Surprising Ketamine Side Effects and Anti-Suicide Benefits

I learned about surprising ketamine side effects from the researcher who first tested it in humans. He had no idea this anesthetic might prevent suicide.

There is tremendous confusion and controversy surrounding a very old drug called ketamine (Ketalar). The FDA first approved Ketalar in 1970 as an injectable anesthetic. It had advantages over existing anesthetics. It was fast acting. Excellent pain relieving properties made it ideal for badly burned patients who needed skin grafts. It was also a good choice for accident victims who required prompt orthopedic surgery. This anesthetic doesn’t lower blood pressure, an important benefit if someone is in shock. Despite its pluses, there were some surprising ketamine side effects.

Surprising Ketamine Side Effects:

When drug companies test medications on animals they can measure lots of bodily functions. One thing they cannot do, however, is ask the animal how it is feeling. It came as a surprise to investigators to discover that Ketalar caused a “dissociative” brain reaction during recovery.

I (Joe G.) have long had a personal interest in this drug because my advisor and professor of neuropharmacology at the Univeristy of Michigan was Edward Domino, MD. He was the lead author on the first published paper about ketamine in humans.

In 1965 Dr. Domino and his colleagues published a paper about an exciting new drug labeled CI-581 (Clinical Pharmacology and Therapeutics, May-June, 1965). It was, as far as I can tell, the first use of the term “dissociative anesthetic.” They described what they observed this way:

“The syndrome immediately following the administration of the drug was of interest. Usually the subject was asked to keep his eyes closed during the procedure. Within a minute after drug injection, the subject reported numbness of the entire body, although sensation to touch remained intact. After 1.0 mg. per kilogram or more of CI-581, the subject would open his eyes and at the same time lose contact with the environment…

Recovery: Odd Ketamine Side Effects:

Dr. Domino, et al, went on to describe surprising ketamine side effects during the return to consciousness:

“During the recovery period the subjects showed considerable variability in psychic reaction. Some were completely oriented in time and place and showed no significant changes. Others showed marked alteration in mood and affect, some becoming apprehensive and aggressive and others markedly withdrawn. Almost all the subjects felt entirely numb, and in extreme instances stated that they had no arms or legs, or that they were dead. If they were touched, however, or moved, such stimuli were perceived….Other reactions noted included feelings of estrangement or isolation, negativism, hostility, apathy, drowsiness, inebriation, hypnogenic states, and repetitive motor behavior.

“At times some of the subjects had vivid dreamlike experiences or frank hallucinations. Some of these involved the recall of television programs or motion pictures seen a few days before, or they were at home with their relatives, or were in outer space, and so on. Some of these phenomena were so real that the subjects could not be certain they had not actually occurred.

“Usually these psychological aberrations subsided completely within a half hour after awakening. The subjects gradually became well oriented and frequently expressed amazement at the experience; most found the experience pleasant and were willing to undergo a second experiment, although 2 refused to continue.”

The Pros of Ketamine:

Dr. Domino explained to me and the other grad students in the department of pharmacology at the Univeristy of Michigan that ketamine was remarkable because it produced “profound analgesia.” The unusual pain-relieving properties of the drug made it highly desirable for procedures that were terribly uncomfortable.

Dr. Domino noted that the experimental subjects who received the drug reported “changes in mood, body image, and affect, and some reported vivid dreams/or hallucinations.” These surprising ketamine side effects were of concern to clinicians and no doubt to the drug company developing ketamine.

We were told that if patients were put in special recovery rooms after surgery with the lights dimmed and with no physical stimulation from nurses, they would often reorient to their bodies more gradually. This allowed for the dissociative state to wear off without some of the complications initially reported after the coma of anesthesia began to wear off.

Other Ketamine Side Effects:

In his original paper in 1965 Dr. Domino reported that subjects experienced watery eyes and profuse sweating. Nystagmus (uncontrollable eye movements) was common along with visual disturbances. Other ketamine side effects include excessive salivation, indigestion, nausea and vomiting. Blood pressure can go up along with heart rate. Some people also note muscle twitching.

Although anesthesiologists still use ketamine in certain circumstances, it has lost favor over the decades. Part of the reason may be that the recovery process can be challenging for busy hospital routine. We suspect that the strange psychological side effects, including hallucinations, also worry some anesthesiologists.

Unexpected Benefits of Ketamine:

When a person feels suicidal, seconds count. Delays could mean a life lost. But what do health professionals have to offer in an emergency?

Until recently, there hasn’t been an effective, fast-acting medication to ease severe depression or counteract thoughts of suicide. Traditional antidepressants can take six weeks or longer to act. That’s why there is growing excitement about the use of ketamine to treat suicidal ideation.

Interrupting Suicidal Thoughts:

A study published in The American Journal of Psychiatry (online, Dec. 5, 2017) demonstrated that a ketamine infusion can banish suicidal thoughts within hours for some people.  That’s remarkable.

In this trial, 80 people were randomized to receive either ketamine or a benzodiazepine called midazolam. In this double-blind research, both groups got their medicine by intravenous infusion. Not only did ketamine help ease major depression, it also reduced suicidal thoughts directly.

Longer Lasting Benefits:

One of the unexpected results of this single-infusion clinical trial was the persistence of the benefit. Most other research has suggested that ketamine loses its antidepressant activity after a week or two. In this study, the improvement lasted for at least six weeks.

The implications of this research are profound. Emergency rooms are overwhelmed with severely depressed patients. Hospitals frequently do not have enough beds to care for suicidal patients. They may be left in the waiting room or in the hallway for days until a room becomes available. Even then, treatments are slow to kick in.

Now that intravenous ketamine infusions have been shown to control suicidal thoughts, emergency physicians may feel justified in administering the drug to desperate patients on the spot. There is a downside, however. You cannot just give a suicidal patient ketamine and walk away. Such patients require intense supervision and continued care. Once the ketamine wears off, they could end up back where they started or worse if there is not monitoring and further treatment.

Ketamine: Not FDA Approved for Depression!

Ketamine is not approved by the FDA for treating depression or easing suicidal thoughts. As a result, many clinicians may be uncomfortable administering it. Only those who are experienced with such treatment should consider prescribing this off-label use.

This is not the first study of ketamine to show promise. A meta-analysis of five trials found that ketamine “showed a large and consistent decrease of suicidal ideation” (Neuroscience and Biobehavioral Reviews, June, 2017).  Other reviews also report that ketamine has a significant effect on suicidal thoughts (American Journal of Psychiatry, online Oct. 3, 2017).

Readers Respond:

We heard this from one reader who has received ketamine infusions:

“I feel frantically discouraged when I am too depressed to feel in control of my mind, body and ability to re-join life. So often, depressed people like me are shunted from hospital to hospital and given drugs that just don’t work. Ketamine is the only medicine that keeps me steady so I don’t want to jump off the nearest bridge.”

Lyn in Phoenix got ketamine during a colonoscopy:

“I was given ketamine by an anesthesiologist when he could not get into my veins for a colonoscopy. I did not come to afterwards. They sent me home anyway.

“My husband managed to get me in the house where I laid on the floor for twelve hours, throwing up occasionally. For the next three days I seemed to have Alzheimers. I kept asking the same questions over and over, I was told later. I could hardly get out of bed. My husband was concerned my brain was gone. This is a very dangerous drug. Stay away from it.”

Ketamine for Suicide vs. Surgery:

Lyn either got a very high dose by mistake or was super susceptible to ketamine. It was being used as an anesthetic during the colonoscopy procedure.

When the drug is used to treat suicidal thoughts and depression, the dose is much lower than that used for anesthesia. Still, study volunteers in the most recent study had some mild adverse reactions, especially elevated blood pressure and a spacey feeling during the infusion.

The scientists hope that further research on ketamine will lead to the development of new and better drugs that will act more quickly than current antidepressants to treat seriously suicidal people.

Want to Learn More?

If you would like to get the straight and skinny on the history of ketamine from the horse’s mouth, so to speak, check out this wonderful article by my old mentor, Edward Domino, MD (Anesthesiology, Sept. 2010). In it you will learn the back story on ketamine from a brilliant neuropharmacologist!

Share your own ketamine story below in the comment section.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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I have been trying to deal with depression since high school (I am 77). I have taken many different antidepressants, supplements, and ECTs. In April and May I had a total of seven ECTs. I had to stop having them because they negatively affected my memory and body. They helped a little, but not to where I need to be. I saw the bit about Ketamine nasal spray on TV recently and decided to research it. My conclusion is that the cost will keep me from receiving this treatment even though I believe it would help with my depression and pain – I have bad fibromyalgia. Since it is such an old drug, why is it now allowed to come out with a different name at such a high cost?

I have Ketamine injected into my knees periodically because of issues with osteoporosis, torn meniscus and cartilage. Has worked for me several times for many years. Would love to say I’ve had euphoric feelings but sadly, no.

I was given Ketamine for a colonoscopy long ago… in 2009. When the procedure was completed, I heard my kind gastroenterologist say, “OK, all is well, you can wake up now D… ” But I couldn’t move, couldn’t open my eyes, couldn’t speak. I felt like I was physically thrashing, trying to break out and respond to the doctor, but was paralyzed . I don’t know how long this lasted, it felt like a long time, but when I broke through to groggy wakefulness my doctor was standing by me, where he the procedure was done. He was smiling, telling me all was well – apparently he had no clue how traumatized I was. I have never forgotten the feeling of terror and desperation. I had a colonoscopy 2 yrs. later and asked that a different anesthetic be used. I was told that drug, Ketamine, was no longer used.

I was given Ketamine for a spinal surgery because I am allergic to profofal. It was a very scary experience. I had hallucinations for it seemed like hours, thought I had died, and had vomiting and dry heaves for hours as well. I remember freezing and finally the nurses put some type of heater fan in bed with me. My family said they waited so long to see me they thought there was a problem with the surgery. For sure won’t use that again. Everyone is different so it might be fine for another.

I was given Ketamine for my anesthesia for a routine colonoscopy 10 years ago. When I came to, I experienced the most profound state of well-being I had ever felt in my whole life, throughout which I have experienced Major Depressive Disorder. It was like a miracle. Back then, Ketamine’s anti-depressive action was either not very well-known or was not talked about. I have subsequently heard so much about its off-label use for alleviating severe depression, and my one brief experience confirms its effectiveness for this. Over the last 2 decades, I have come to be able to manage my depression with a couple of pharmaceuticals plus some supplements, which has been life-saving for me. However, the feeling of well-being I had on the Ketamine has never been reached on this regime. I was looking forward to my next colonoscopy (!), which I had this past year so I could once again experience that profound sense of well-being. Unfortunately, afterwards I did not experience this and when I inquired, the nurse said they haven’t Used Ketamine for years as an anesthetic. I was sorely disappointed!

I experienced a similar miraculous effect for 2-3 weeks following dental surgery in which I was told ketamine was used, and the same disappointment that it would not be available for a colonoscopy this year. Although I do not suffer from depression ordinarily, some of my CFS symptoms, especially chronic metabolic fatigue, share symptoms with that condition.

The only thing holding me back from scheduling a course of low dose ketamine infusions at this time is the cost vs duration of its effect. There is not a lot of information on how long the effects may last. It is also expensive for those of us who are denied reimbursement for the cost, which often includes additional travel expenses.

I work in a busy ER as a respiratory therapist. ER docs will use drug for a procedure called consedaton sedation. Over my 10 years of assisting the doctors I have never seen negative effects. RT’s are always on standby with these as the drug can cause respiratory depression. I like the drug as it is very effective, fast acting. It also has a short half life. It wears for very fast.

I received Ketamine after breaking my wrist on a cruise ship. The doctor warned me it would be an Alice-in-Wonderland experience while he took X-rays and set my arm. It was dreamy. I remember talking to my husband, asking “Are you there?” over and over. Not an unpleasant experience, quick recovery and no after effects.

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