How ketamine may help some people with treatment-resistant depression

Ketamine is a Food and Drug Administration-approved anesthetic that, in certain doses, has psychedelic effects.

However, it differs from psychedelics such as LSD and psilocybin in how it affects the brain.

In 2019, the Food and Drug Administration approved a form of this drug, known as S-ketamine (or esketamine), for treatment-resistant depression. This is given as a nasal spray.

When people talk about ketamine, they’re generally referring to the generic form of ketamine used in the new study, also known as racemic ketamine.

In recent years, scientists and physicians have explored the use of ketamine and other psychedelics for treatment-resistant depression. This is a severe form of depression that hasn’t responded to two or more types of antidepressant medication.

Some previous research has found that about a third of people with major depression don’t see a complete improvement in symptoms even after four phases of antidepressant treatment.

Once people fall into that treatment-resistant category, their chances of recovering from depression with the tools we currently have at their disposal mean psychotherapy, antidepressants, and electroconvulsive therapy. [ECT] their chances of long-term recovery are extremely slim, Dr. Dave Rabin, a psychiatrist, neuroscientist and founder of Apollo Neuroscience, told Healthline.

Previous randomized controlled trials have compared ketamine with an inactive placebo or controller for treatment-resistant depression. However, many of these studies had small numbers of participants.

Also, most of these studies used a saline solution as a placebo. This let the participants know whether or not they were receiving ketamine, which could potentially affect the results.

In the new study, the researchers overcame this limitation by comparing ketamine with midazolama sedative that makes people feel relaxed or sleepy but does not improve symptoms of depression.

The researchers also enrolled people who had previously received ECT for their depression, a treatment that is sometimes recommended when antidepressant medications don’t work.

Most [ketamine] the studies exclude people who have had ECT because it’s very difficult for a new treatment to work where ECT hasn’t worked, Loo said.

A recent study published in The New England journal of medicine reported that ketamine worked just as well as ECT for treatment-resistant depression.

To have an alternative for people who are struggling with treatment resistant depression that is not doing a hard electrical reset to the brain [like ECT] it’s something that’s really important to the community and gives people a lot of hope, Rabin said.

Another difference with the new study is that ketamine was given subcutaneously (injected into the skin), rather than by intravenous (IV) infusion. This allowed the researchers to test a delivery method that was easier to do in the clinic.

The nice thing about subcutaneous ketamine is that it has a little more gradual onset of action and gradual decline in action, Dr. Steven Radowitz, chief physician and co-founder of Nushama Psychedelic Wellness in New York City. .

For the new study, researchers recruited 179 people with treatment-resistant depression from mood disorder clinics in Australia and New Zealand.

They randomly assigned people to receive either ketamine or the controller drug, midazolam.

People received two injections a week in the clinic, where they were monitored for about two hours. The treatment lasted for a month. Participants rated their mood at the end of the four weeks and one month later.

Serious adverse events among people taking ketamine in the study were rare, with one major dissociative episode and an auditory hallucination.

Four participants taking ketamine dropped out of the study due to less serious side effects, including skin rashes, increased anxiety, headaches and increased depression.

The expected short-term effects of ketamine treatment, such as increased blood pressure, disappeared within 2 hours of treatment, the researchers reported.

For one group of study participants, researchers started people on a lower dose of ketamine and then increased it over time.

The researchers said they saw better results with this approach than maintaining a constant dose throughout the trial.

Radowitz said that at his clinic, they also increase the dose for patients over time to see how they’re responding and how comfortable they are with the experience.

However, in general, they use a higher dose in his clinic than the one used in the study, which he said was too low.

He also pointed out that the study didn’t seem to take into account a person’s mindset and setting things like music, lighting and wearing masks, all of which are commonly used during psychedelic treatments in clinics.

[Psychedelic] travel is an unusual experience, so it’s important to feel safe when doing these things, Radowitz said. Music is a vital part of psychedelic medicine. So it’s preparing people for the journey and helping them integrate their experience afterward.

Although Radowitz said the new study had a decent result, he thinks they could have gotten better results if the researchers used a higher dose of ketamine and paid more attention to the treatment setting and mindset of the patients.

Dr. David Mahjoubi, an anesthetist and founder of the Ketamine Healing Clinic in Los Angeles and Orange County, said that while he always recommends patients combine ketamine therapy with psychotherapy, some people may do well with drug treatment alone.

Also, not all patients at his clinic suffer from treatment-resistant depression.

Someone with mild depression may want to try ketamine because they don’t want to take a drug they would have to take by mouth every single day and which could have side effects, she told Healthline.

As with the new study, Mahjoubi finds that the long-term benefits of ketamine therapy vary from person to person.

I’ve had patients who have had their initial series of IVs benefit for over a year, he said. But some patients have needed to come back once a month to stay optimized because they feel the benefits diminish after a month.

Mahjoubi also prescribes an at-home nasal ketamine, which people can use as needed to maintain the benefits. This uses racemic ketamine, not the eskatmine version sold under the brand name SPRAVATO.

Rabin agrees that preparing people for treatment with ketamine or any psychedelic treatment and helping them integrate their experience afterwards can improve outcomes.

This could include psychotherapy, cognitive behavioral therapy, or calming touch therapy.

Apollo Neuroscience has developed a wearable device that uses low-frequency sound waves to deliver soothing vibrations.

Rabin said the device is being used by doctors in the United States and Canada in conjunction with psychedelic therapy to improve treatment responses and patient comfort. It’s also being tested in a clinical trial of psychedelic therapy MDMA, he said she.

By adding these types of approaches, people are able to integrate what they experience in treatment into their lives more effectively, Rabin said.

Also, what we were seeing is that when you add that therapeutic component to the practice of psychedelic medicine, whether it’s MDMA, ketamine, or any other psychedelic medicine, it seems like the effect is stronger and more long-lasting, he said.