Ketamine & Depression: How it Works - Yale Medicine Explains

Depression is one of the most common and most debilitating mental health disorders, affecting some 17 million adults in the US. It also continues to be a misunderstood, often hard-to-treat illness. Researchers have worked for decades to better understand the neurobiology underpinning depression. For patients with severe, treatment-resistant depression, spending months or even years searching for good treatments can be totally disabling. The prevailing hypothesis for years was that depression was regulated by the neurotransmitter’s serotonin and norepinephrine. Eventually, data began to suggest that maybe something much larger and more global was involved in the brain to account for depression, which led researchers to begin working with glutamate and GABA, the most abundant neurotransmitters in the brain. These chemicals are involved in neuroplasticity – the brain’s ability to adapt to change and protect itself against stressful events. Neuroplasticity is a physical thing, too: it manifests itself “in terms of synapses, how these neurons are actually touching each other and communicating with each other,” explains Gerard Sanacora, PhD, MD, Director of the Yale Depression Research Program. “And we know that in depression, the number and strength of these interconnections decreases,” says Rachel Katz, MD, a professor of Clinical Psychiatry at Yale. Ketamine – originally developed and still used as an anesthetic – works on those two neurotransmitters and was discovered to have rapid antidepressant effects. Some experience an improvement in symptoms in 24 hours or less. “We think that one of the things that Ketamine does, that helps to explain its antidepressant effects, is help the brain to regrow the synapses, the connections between nerve cells,” says John Krystal, MD, Chair of the Department of Psychiatry at Yale. Because Ketamine seems to work on a totally different system in the brain than typical antidepressants, “that may be why Ketamine works so well, even for patients who have not had success with a number of standard antidepressants,” says Dr. Katz. Ketamine as a treatment for depression gained FDA approval last year with the release of Spravato (esketamine), and for now, it remains a treatment reserved for patients who haven’t found success with at least two other antidepressant treatments. Dr. Sanacora explains that other treatments, including cognitive behavioral therapy, are important to use in conjunction with ketamine, “to develop new ways of adapting and having new cognitive strategies of dealing with future stressors to prevent relapse.” New therapies like ketamine are changing how depression is understood, and may pave the way for future research that helps us understand the brain in all of its complexity.

[odonnellm]

Just had my first treatment. I’m a combat vet and have been struggling with severe MDD with psychotic features/PTSD for years and I’m here to say my life has changed. The day after my treatment I woke up at 4am and for the first time in at least 30 yrs without crippling anxiety or depression as well as anger. I was completely relaxed with hope for my family and my future. I have 5 more treatments and I’m excited to see what’s to come. I was nervous as hell, to be honest, but, it was one of the best experiences of my life. I felt so connected with everything my wife was with me in support. It was such an emotional experience. It’s very expensive and not covered by insurance in the US but worth it 100 percent.
Had my second session and It was an amazing experience, different in some way I felt a bit more out into the mystic I now call it. I had a moment of WTF but it wasn’t frightening it was amazing. I noticed that as if the spiritual realm I was in allowed me to accept awesomely incites into what my life truly was meant to be like free. Free of depression, anxiety, pain. Very comfortable. I was feeling nauseous as hell the next day but it was manageable somewhat considering my experience. Also, I had a Flood of overwhelming sadness related to my combat experiences in Iraq. For the first time in almost 20 yrs, I was able to grieve the loss of my best friend as well as other war-related issues I had. After talking with my DR, and therapist I was able to process that. Incredible as if the piece of my soul that was left in Iraq was being returned back to me.


Od_Arts
10 days ago
My 3rd treatment was so powerful. I feel as if all exposures of trauma I've experienced are being reset with truth and recycled into my subconscious. My Dr. hooked me up with nausea med through drip and has worked wonders. My anxiety and depression have subsided big-time. I do experience some anger but it disappears quickly and turns into these moments of clarity and electricity throughout my mind. No constantly nagging intrusive thoughts. If I have one I deal with it as false and move forward and that's huge. Suicidal ideation was a kind of ebb and flow with MDD my least favorite part. I've had 2 again I notice it and deal with it as false and move on. This has been an incredible journey so far. I've had to deal with some shit moments but expect that on the in-between speaking for myself only. I can see how each journey builds onto one another. I have hope now and feel like I can take on the world. This experience also reverberates throughout my family. Look forward to the next.



4th treatment today was awesome! Very linear rather than organic I feel on the right track it’s been a minute)

5th treatment was so awesome! My depression and anxiety have completely subsided. I have newfound motivation my artwork has transformed. I will be one year sober from alcohol and I have had no cravings. The real work I have noticed is the days after treatment. I can tell the effects carry on to my family and that’s most important to me. I'm not stuck anymore so I can be more supportive of my loved ones instead of being crippled with mental health issues and the cycle of addiction. It’s not easy, I had to be open and honest with myself really wanting to do the internal work that it takes to move past trauma. This works. This works.

6th treatment was epic. I had a rough couple of days after my fifth treatment, I had a flashback due to an anniversary date what I noticed was even though it was a rough experience I was able to get past it in a healthy way and the event didn't force me down a hole for months or even yrs on end. I am even optimistic about my future in taking better care of myself as well as taking my art to a new level. Overall this treatment has worked very well for me. My wife, my Dr., and his wife have been the best support during this time. I would absolutely recommend CBT or some one-on-one therapy will getting the infusions to help make sense of the transformations that come with each unique experience. There is no more crippling depression and suicidal ideation. I feel at ease and at peace with myself. I know I will have to go back for booster infusions and that is ok. The only downside that I can say doesn't have to do with the effectiveness of the treatment but the cost. I consider myself in the lower rungs of the middle class as of now I hope one day soon this can be covered by insurance so there are no barriers between economic classes. Everyone should have access. Thanks for reading.

[beikdw]

Why is this not used as a first treatment for depression? Regrowth and interconnections in the brain sounds better than relying on constant psychostimulation using SSRI for potentially years.

[shimel]

One treatment in, and after 30 years of depression, I feel free and normal. No more sensations of heaviness or anxiety in my chest.

[APOLLINAIREBARTHOLOMIEU]

Psilocybin saved my life. I was addicted to heroin for 15 years and after Psilocybin treatment I will be 3 years clean in September. I have zero cravings. This is something that truly needs to be more broadly used in addiction treatment.

[arkgawilson]

Off antidepressants for the first time in 18 years. Changed my life.

[yanpisar]

This is incredibly underrated and underutilized as a tool for people who are genuinely struggling in life

[liljohntownsend]

Hope is a powerful thing my first treatment is tomorrow

[noaha]

Been mixing this with lions mane, ginseng, and ginko biloba extracts. Ketamine therapy has always helped me but now I'm seeing huge rapid changes. I'm trying to get a job now for the first time in years!

[johntnguyen]

Psychedelic mushrooms really healed me years back. Totally got rid of depression, anxiety and illicit pill addiction. I’ve been looking to try some recently but I can’t find anywhere to source.

[BigDaddyB]

4 more days I start my Ketamine treatment!! Im so hopeful to be able to regain a sense of joy in my life again!

[MsRayH]

Ive been on antidepressants and/or anti-anxiety meds for the most of 20 years. I suffered a lot of trauma when i was younger so it's caused some issues to say the least. On friday I start my first treatment with a doctor in conjunction with my therapist. I'm so sroked and I've been looking forward to this for months. I've read lots of great comments and it's making me even more excited. I cant even remember what it feels like to "be happy" or "at peace" for real. Wiah me luck!

[tnfatbelly]

This treatment has brought me back to life from severe chronic pain and depression/anxiety!!! I’m only 3 treatments in and feel better than I have in years!

[swimmer]

I’m currently half way through my ketamine therapy. As a combat veteran, many things linger. After 10+ years of doing, psych therapy, various antidepressants and so forth. I’ve found ketamine to have an unexplainable success with some of my most serious issues. I relate it to electricity when people ask me how it works, I explain I don’t know how ketamine works, just as the same as I don’t know what exactly electricity works however I enjoy the benefits of it. I wish I would have known about it sooner.

[konne]

I didn't know, but aparently ive got slight manic depression, work in hospitality, after loosing my job girlfriend house and few more things I don't want to mention in public, i discovered Ketamin, its like a positivity BOOST... for me literally instantly iam able to think clear, productive, logic creative, this stuff works, i have got my life and routine back❤

[susanmenegus]

They gave me that at the hospital when I got surgery it's the happiest I've ever been in my life

[tessbrand]

Praying for a way to afford it. I’ve had 7 infusions. Money is becoming an issue at $450 a session. It helped me and was very noticeable in every aspect of my life. My major depression has robbed me of far too many years. My first treatment was 4/29 . I became a new me about the 5th treatment. I want that back. It felt so good to live!

[stephenpowstinger]

I’m comforted to hear a prestigious institution support ketamine use. I had a course of it awhile back. Short vid. But no one greeted me with “my you look better” afterwards. I think it helped but I’m still dragging many times.

[grtzam]

I wish they mentioned it's use in studies to be a preventive measure for Alzheimer's/Dementia.

[jacobdraves]

Ever since an LSD trip completely rid me of my nicotine cravings, I’ve been a promoter of psychedelic therapy.

[Usedwtm]

My first infusion is in 6 days. Im honestly terrified. Psychedelics scare and intimidate me, but my family and my doctors think it'll save my life. I want this to work so badly. Not only for my psychiatric disorders, but I have pretty bad chronic pain.