‘Club Drug’ Ketamine Lifts Depression in Hours

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The largest study to date confirms that ketamine — a “club drug” that is also legally used as an anesthetic — could be a quick and effective way to relieve depression.

The results were presented at the annual meeting of the American Psychiatric Association and represent growing excitement about ketamine’s potential. The study included 72 patients who had previously failed to respond to at least two other medications. After receiving a single intravenous (IV) dose of ketamine, 64% of patients reported fewer depression symptoms within one day compared to 28% of those given midazolam — an anesthetic drug that was used as a control.

“[This research] reports the largest controlled evaluation of the antidepressant effects of ketamine to date,” says Dr. John Krystal, professor of psychiatry at Yale, who published the first study in 2000 suggesting that ketamine could quickly lift depression, but was not associated with this trial.

Antidepressants typically take weeks to improve mood — and that’s a time when people with the disorder are at an especially high risk of suicide. “Among people who respond to antidepressants, it takes on average 7 weeks to produce this response,” Krystal says, “When simply getting through a single day can be difficult, waiting 7 weeks to get better can be daunting.” Ketamine— and similar drugs currently being tested by pharmaceutical companies could help relieve suffering faster and potentially reduce the suicide risk associated with the mood disorder.

And because the doses used were lower than those taken by clubbers or used in anesthesia, most patients didn’t have the extreme experiences of “out of body” sensations or profoundly distorted perceptions of reality.  “Nobody freaked out,” says Murrough, adding that most described the experience of the infusion as being similar to having had a few drinks. About 10%, however, did have some dissociative effects.  “One patient [reported] wondering whether time still existed during the infusion,” he says.

The results are especially noteworthy because ketamine was compared to another anesthetic with similar psychoactive effects, not just a placebo. Such comparisons are important because drugs that result in highly noticeable responses like sedation also tend to have strong placebo effects. Researchers had argued that without such a comparison, it would be difficult to tell whether ketamine was actually relieving depression.

“This design was elegant because midazolam briefly made patients feel better, but did not produce a real antidepressant effect,” Krystal says, “In contrast, ketamine produced the robust antidepressant effects that have been observed in every study of ketamine since our initial preliminary observations.  This is the first direct evidence that the antidepressant effects of ketamine are specific, increasing our confidence in importance of this clinical observations.”

MORE: A Mystery Partly Solved: How the ‘Club Drug’ Ketamine Lifts Depression So Quickly

Since the study has not been published, however, the results have not yet been subject to peer review. But Krystal and others are encouraged by the apparently lasting effects of the drug; the study showed that seven days after the infusion, 46% of those who received ketamine were still experiencing significant relief— compared to just 18% of those who received the midazolam.

The findings also follow about half a dozen smaller trials that tested the drug for depression or bipolar disorder. Murrough and his colleagues also published a study last year in Biological Psychiatry that could pave the way for broader use of the drug. In that analysis, his team examined whether ketamine could be used repeatedly for longer term results, perhaps as a replacement for, or addition to, electroconvulsive therapy (ECT). In that study, 24 patients with treatment-resistant depression who were not taking any other medications received several daily doses of ketamine; after 12 days, 71% of the patients showed a 50% reduction in depression symptoms, with relief typically coming within 2 hours of the treatment.  On average, the patients who responded remained well for 18 days following the last infusion.

But because ketamine distorts consciousness, it likely would not be practical as a daily medication, as Prozac is currently used. In cases of profoundly disabling depression, however, it might be helpful if given several days a week, the way ECT is now prescribed.  While ECT is the best existing treatment for cases of depression that do not respond to medication and therapy, the stimulation can interfere with memory and it requires general anesthesia. Murrough envisions ketamine could be administered in conjunction with talk therapy and in combination with other medications to try to maintain recovery.

In fact, since ketamine is already FDA-approved, some clinicians have started to offer infusions to their patients, but that’s not a practice that Murrough condones. “There are physicians carrying out this procedure in nearly every major American city,” Krystal notes, “[But] I think that ketamine infusion is still an experimental procedure.”

Indeed, Krystal’s colleagues recently reported some significant negative side effects in his trial of using ketamine to treat obsessive-compulsive disorder (OCD). Two of three participants who had OCD, who did not have current depression but had suffered from it in the past, developed new symptoms the day after ketamine treatment, which included suicidal thoughts, anxiety and severe distress.

MORE: Ketamine for Depression: The Most Important Advance in Field in 50 Years?

The researchers agree that while promising, ketamine-based therapy is probably still best conducted in an experimental setting— but that any clinicians who use it outside of research must, at the very minimum, carefully monitor patients. Krystal is planning to urge the National Institute on Mental Health to collect more data on all patients currently being treated for mental illness with ketamine. “The largest study of repeated ketamine administration ever published has only 24 patients in it,” he says, “This is an extremely thin and somewhat risky evidence-base to launch a national treatment program.”

With more data, however, researchers may become more confident in how best— and safely— to use the drug. And the latest study is an important first step toward that goal. “It seems that a new antidepressant approach has been identified that may expand the scope of effective antidepressant treatment,” Krystal says, “We look forward to larger and more definitive clinical trials that will help to determine whether more patients will be effectively treated through this mechanism and whether the possibility of rapid improvements in depression substantially reduces the burden of this disease.”

8 comments
waltbarnes3
waltbarnes3

My son is receiving ketamine in a nose spray. He is a teenager with Bipolar. He takes it every three days. BP symptoms are gone! No more fear, aggression, sleeping problems, food craving, cursing, mania, or OCD tendencies. It is amazing!!!!!!!!! We have been on ketamine 3 months. Time will tell.

nickguy
nickguy

You generally should not give Hallucinogenic DRUG to Mentally Ill Patients, don't you think there are more logical alternatives to be taken. I was on a ketamine study for a year, and that drug is addictive as hell and very toxic to your bladder and stomach tissues. I was essentially a Guinea pig just so they could pass the trials, and there was no understanding of how the doses should be prescribed. This evidentially lead to a continual increase in the amount taken over 12 months.  The only benefit this drug can provide to patients is it gets them high enough to be "disassociated" with their negative feelings. You taking drug that literally causes out of body experiences, and to a certain degree exploiting this distance from normal consciences as a way to combat depression. Not only was this used multiple times a week, its primary clientele was a group of children ages 5-15!!

IBM
IBM

MaryBostian, I'm very sorry ketamine provided no relief for you, but I too was treated with ketamine and had a vastly different result.  My 30+ year depression was agony (constantly suicidal, no relationships, unable to work, severe anxiety, etc) and no treatment ever helped at all.  Since the mid-80s I saw many psychotherapists and psychiatrists, tried every type of antidepressant, practiced mindfulness and meditation -- you name it.  I heard about ketamine last December and volunteered for an inpatient study at the National Institutes of Health, where I received a ketamine infusion.  Within one hour all of my symptoms were completely gone.  All but one of my fellow patients had the same response.  This study consists of patients with extreme cases who have failed to respond to multiple treatments.  People who have suffered for decades and have lost nearly everything important to us:  spouses, families, careers, homes.  And now we use words like "incredible" and "miraculous" to describe the relief that ketamine provided us.  The relief from the initial infusion lasted about two weeks for me.  I quickly found a doctor who uses ketamine in clinical practice and have been receiving ongoing ketamine treatment ever since.  It has transformed my life in a way I never thought possible.  You cannot imagine the sensation of decades of suffering rapidly draining away, and being able to engage in normal, relaxed human interactions for the first time in my 47 years.  I am in touch with my fellow NIH patients, and they report essentially the same as me.

Readers of this post must understand that "depression" is a blanket term that describes a broad set of symptoms.  People like me, whose symptoms are primarily due to a specific brain chemistry malfunction (overstimulation of NMDA receptors by glutamate neurotransmitters) respond immediately and strongly to ketamine.  But there are many other things that also will lead to a diagnosis of "depression", and some of those are things that ketamine won't fix.  Still, if you read all the published results to date, the ketamine response rate in double-blind studies ranges from 68-85%, which is astonishingly high.  I very much hope you find something that will help, MaryBostonian.  It might interest you to know that some NIH study subjects who failed to respond to ketamine DID respond very well to scopolamine in a parallel study.

Many people in my life told me over the decades to "snap out of it", or adjust my "attitude", and they judged me to have poor character because I couldn't take care of myself, or hold a job, or even maintain friendships.  I don't blame them.  They cannot understand the difficulty and pain and fear the simplest tasks pose when your brain has my kind of permanent, physical/chemical malfunction.  Ketamine repaired the very specific underlying physical problem in my brain, which eased my suffering and made it easy to do the small normal things that make up most of life.  In doing so it also affirmed that my problem wasn't poor character, it was defective brain chemistry.  I didn't suffer because I'm a rotten person; I suffered because I had a definite physical medical problem.  Finally, more than halfway through my life, there is at last an effective way to treat that problem.

The number of doctors using ketamine in clinical practice is growing rapidly.  To those who read this post while suffering unbearable, never-ending depression that has never responded to any treatment: find a doctor who gives ketamine infusions, or intranasal ketamine, or else volunteer for a ketamine study.  The research may one day yield a perfect drug that works like ketamine, with no side effects, in pill form. I’ll be the first in line. For now, though, ketamine is saving lives and relieving immense suffering.

TerryChestnutt
TerryChestnutt

Well said,, MaryBostian. It very sounds like you know the turf. Thank You for coming forward.

MaryBostian
MaryBostian

I was given ketamine for "treatment resistant" depression. A month later I attempted suicide. After coming so close to death, a social worker suggested a different approach to therapy which has been the primary factor, albeit a long process, in successfully treating my depression. This is a culture of quick fixes. I agree that saving lives is of obvious utmost importance. My goodness, they may as well have given me hashish to smoke. That would have worked, too, but only temporarily. As a recovering addict, in my past I indulged in a number of substances that proved much more pleasing than the distortions and altered mind states that ketamine provided. It is in reality that I have chosen to live and recover. I regressed when the effects of ketamine eventually wore off. Drugs are abused, because they alter our state of mind. But unless we spend our lives high, we must learn to live in this world, in our minds, in our spirits. Obviously we must keep people who are at risk from suicide safe, until they gain hope. My father and brother used mind altering drugs to medicate their depression, because in the short term they do the trick. But they were deeply and negatively affected. Both took their own lives. Distorted thinking brings distorted emotions, such as hopelessness and desperation for relief. Quick fixes do not last. How long were these subjects followed? If psychotropic medication fails time after time, why get high until the failing meds hopefully work? Therapy, such as cognitive behavioral or dialectical behavioral, changes thinking, bringing about emotional change. These therapies cannot be successful in altered states.I wish that while patients are locked up to protect themselves, the approach would be to begin a long lasting, even permanent treatment such as the above mentioned therapies. I speak not only from personal experience, but from educated and intelligent reason. I still, and may always, use anti- depressants, mood stabilizers, and even anti- psychotics that help to prevent altered mind states. I so hope that someday we will stop the madness of trying to cure madness with drugs that cause madness.

MaryBostian
MaryBostian

I was given ketamine for "treatment resistant" depression. A month later I attempted suicide. After coming so close to death, a social worker suggested a different approach to therapy which has been the primary factor, albeit a long process, in successfully treating my depression.

This is a culture of quick fixes. I agree that saving lives is of obvious utmost importance. My goodness, they may as well have given me hashish to smoke. That would have worked, too, but only temporarily. As a recovering addict, in my past I indulged in a number of substances that proved much more pleasing than the distortions and altered mind states that ketamine provided. It is in reality that I have chosen to live and recover. I regressed when the effects of ketamine eventually wore off.

Drugs are abused, because they alter our state of mind. But unless we spend our lives high, we must learn to live in this world, in our minds, in our spirits.

Obviously we must keep people who are at risk from suicide safe, until they gain hope. My father and brother used mind altering drugs to medicate their depression, because in the short term they do the trick. But they were deeply and negatively affected. Both took their own lives.

Distorted thinking brings distorted emotions, such as hopelessness and desperation for relief. Quick fixes do not last. How long were these subjects followed? If psychotropic medication fails time after time, why get high until the failing meds hopefully work? Therapy, such as cognitive behavioral or dialectical behavioral, changes thinking, bringing about emotional change. These therapies cannot be successful in altered states.

I wish that while patients are locked up to protect themselves, the approach would be to begin a long lasting, even permanent treatment such as the above mentioned therapies.

I speak not only from personal experience, but from educated and intelligent reason.

I still, and may always, use anti- depressants, mood stabilizers, and even anti- psychotics that help to prevent altered mind states. I so hope that someday we will stop the madness of trying to cure madness with drugs that cause madness.

MaryBostian
MaryBostian

IMD,

I can relate to everything you said about your experiences with depression. I am wondering if my different reaction to ketamine was due to me having bipolar 1, severe with psychotic features. That would be good for psychiatrists to be able to study that. I have had two courses of ECT in my life, literally countless hospitalizations including one for eight months, and have been put into a nursing home for "the rest of my life". I do not know why I was blessed to have gained value in my life and know it. I respect and am glad to hear your successful treatment. I feel the same about my life being miraculous and incredible. I guess it just goes to show that we, as people with mental illness, cannot be put in a box or categorized. Thank you for your comment. By reading it I realize that ketamine very well may be worth a try for those of us who have run the gamut of any other treatment that were never successful. I am not damaged by my several treatments other than the trauma I experienced. That trauma I was indeed able to work through.

Your story is, just as I know mine is, very encouraging and inspiring.