Study answers why ketamine helps depression, offers target for safer therapy

June 21, 2017, UT Southwestern Medical Center
3-D model of Ketamine. Credit: Wikipedia

UT Southwestern Medical Center scientists have identified a key protein that helps trigger ketamine's rapid antidepressant effects in the brain, a crucial step to developing alternative treatments to the controversial drug being dispensed in a growing number of clinics across the country.

Ketamine is drawing intense interest in the psychiatric field after multiple studies have demonstrated it can quickly stabilize severely depressed patients. But ketamine - sometimes illicitly used for its psychedelic properties - could also impede memory and other functions, spurring scientists to identify new drugs that would safely replicate its antidepressant response without the unwanted side effects.

A new study from the Peter O'Donnell Jr. Brain Institute has jumpstarted this effort in earnest by answering a question vital to guiding future research: What proteins in the brain does ketamine target to achieve its effects?

"Now that we have a target in place, we can study the pathway and develop drugs that safely induce the antidepressant effect," said Dr. Lisa Monteggia, Professor of Neuroscience at UT Southwestern's O'Donnell Brain Institute.

The study published in Nature shows that ketamine blocks a protein responsible for a range of normal brain functions. The blocking of the N-methyl-D-aspartate (NMDA) receptor creates the initial antidepressant reaction, and a metabolite of ketamine is responsible for extending the duration of the .

The blocking of the receptor also induces many of ketamine's hallucinogenic responses. The - used for decades as an anesthetic - can distort the senses and impair coordination.

But if taken with proper medical care, ketamine may help severely depressed or suicidal patients in need of a quick, effective treatment, Dr. Monteggia said.

Studies have shown ketamine can stabilize patients within a couple of hours, compared to other antidepressants that often take a few weeks to produce a response - if a response is induced at all.

"Patients are demanding ketamine, and they are willing to take the risk of potential side effects just to feel better," Dr. Monteggia said. "This demand is overriding all the questions we still have about ketamine. How often can you have an infusion? How long can it last? There are a lot of aspects regarding how ketamine acts that are still unclear."

Dr. Monteggia's lab continues to answer these questions as UT Southwestern conducts two clinical trials with ketamine, including an effort to administer the drug through a nasal spray as opposed to intravenous infusions.

The results of these trials will have major implications for the millions of depressed patients seeking help, in particular those who have yet to find a medication that works.

A major national study UT Southwestern led more than a decade ago (STAR*D) yielded insight into the prevalence of the problem: Up to a third of depressed patients don't improve upon taking their first medication, and about 40 percent of people who start taking antidepressants stop taking them within three months.

Ketamine, due to the potential side effects, is mainly being explored as a treatment only after other antidepressants have failed. But for on the brink of giving up, waiting weeks to months to find the right therapy may not be an option.

"Ketamine opens the door to understanding how to achieve rapid action and to stabilize people quickly. Because the (NMDA) receptor that is the target of is not involved in how other classical serotonin-based antidepressants work, our study opens up a new avenue of drug discovery," said Dr. Monteggia, who holds the Ginny and John Eulich Professorship in Autism Spectrum Disorders.

Explore further: Antidepressant effects of ketamine

More information: Kanzo Suzuki et al. Effects of a ketamine metabolite on synaptic NMDAR function, Nature (2017). DOI: 10.1038/nature22084

Related Stories

Antidepressant effects of ketamine

December 8, 2016
New preclinical evidence was put forward by investigators in a series of presentations at the recent meeting of the American College of Neuropsychopharmacology suggest that the a metabolite of ketamine can produce antidepressant-like ...

Research shows why ketamine is an effective antidepressant but memantine is not

May 27, 2014
(Medical Xpress)—Ketamine is a fast-acting antidepressant. However, it can create symptoms that mimic psychosis. Therefore, doctors don't give it to depressed patients. Memantine, a similar drug, does not have psychotomimetic ...

Is ketamine a panacea for depression?

May 18, 2017
Researchers have long been intrigued by the antidepressant qualities of the club drug ketamine. Known on the street as "Special K," the drug is taken by partiers for its brief dissociative hallucinogenic effect, but it is ...

Ketamine helps see how the brain works in clinical depression

June 16, 2011
(Medical Xpress) -- In a new study published in Nature, Lisa Monteggia from the University of Texas Southwestern Medical Center looks at how the drug ketamine, typically used as an anesthetic or a popular recreational drug ...

Researchers uncover new insights into developing rapid-acting antidepressant for treatment-resistant depression

June 12, 2014
UT Southwestern Medical Center researchers have generated fresh insights that could aid in the development of rapid-acting antidepressants for treatment-resistant depression.

Ketamine produces rapid-onset antidepressant action

January 5, 2015
(HealthDay)—Ketamine has rapid-onset antidepressant action, although the mechanism of its positive effect is currently unclear, according to research published online Dec. 26 in the Journal of Clinical Pharmacy and Therapeutics.

Recommended for you

Psychiatric disorders share an underlying genetic basis

June 21, 2018
Psychiatric disorders such as schizophrenia and bipolar disorder often run in families. In a new international collaboration, researchers explored the genetic connections between these and other disorders of the brain at ...

One year of school comes with an IQ bump, meta-analysis shows

June 21, 2018
A year of schooling leaves students with new knowledge, and it also equates with a small but noticeable increase to students' IQ, according to a systematic meta-analysis published in Psychological Science, a journal of the ...

Ketamine acts fast to treat depression and its effects last—but how?

June 21, 2018
In contrast to most antidepressant medications, which can take several weeks to reduce depressive symptoms, ketamine—a commonly used veterinary anesthetic—can lift a person out of a deep depression within minutes of its ...

New study debunks Dale Carnegie advice to 'put yourself in their shoes'

June 21, 2018
Putting yourself in someone else's shoes and relying on intuition or "gut instinct" isn't an accurate way to determine what they're thinking or feeling," say researchers from Ben-Gurion University of the Negev (BGU), the ...

Mindful movement may help lower stress, anxiety

June 21, 2018
Taking a walk may be a good opportunity to mentally review your to-do list, but using the time to instead be more mindful of your breathing and surroundings may help boost your wellbeing, according to researchers.

Brain tingles—first study of its kind reveals physiological benefits of ASMR

June 21, 2018
Autonomous sensory meridian response (ASMR) – the relaxing 'brain tingles' experienced by some people in response to specific triggers, such as whispering, tapping and slow hand movements – may have benefits for both ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

catNgunNbmwaddict
5 / 5 (2) Jun 21, 2017
Great for two of my bipolar neighbors and a few of my exs who are nuttier than squirrel turds.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.