Introduction to Ketamine Therapy

Major Depressive Disorder, Bipolar Disorder, and Post-traumatic Stress Disorder (PTSD) are among the most painful experiences a human being can endure – so painful, in fact, that each year over one million people choose suicide rather than suffering one more day with these conditions. The general public often thinks wrongly of these conditions as purely emotional, but sufferers endure serious and debilitating physical symptoms that impede their ability to function normally, in addition to the emotional pain amplified by those symptoms. People with the very worst cases do not respond to standard treatments. For them, depression/bipolar/PTSD is often a life sentence – or a death sentence – but ketamine offers a new source of hope.

Use the Learn menu at the top of the page to read about the following topics:

Route of Administration Explains why the method used to put ketamine in the body is so important.

Cost

Explains why the treatment costs what it does, and why it isn’t covered by insurance yet. The Infusion Experience

Describes the experience of undergoing a ketamine infusion. The Relief Experience

Explains the subtle way relief reveals itself and the way it improves function and mood. Getting the Most Out of Treatment

Practical tips to help you maximize the benefits of ketamine therapy. Opposition Explains why widespread use of ketamine therapy is opposed by Big Pharma, some ketamine researchers, and many psychiatrists.

This site focuses on extreme cases of depression, bipolar disorder, and PTSD. The word depression is casually used to describe any kind of low mood, but on this site it always means treatment-resistant major depressive disorder and is not meant to cover situational or temporary depression caused, for example, by a failing marriage or a toxic work environment. Anywhere on this site where we say patients like us, we mean patients with treatment-resistant major depression or bipolar or PTSD – grave medical conditions unresponsive to medication or therapy and involving years of intense suffering and extreme physical symptoms that dramatically impair one’s ability to function. It is patients like us who founded the Ketamine Advocacy Network and created this website.

For the past 15 years researchers have known that tiny doses of ketamine can rapidly relieve depression symptoms when delivered via slow intravenous infusion. The first scholarly paper describing this discovery was published by Yale in 2000. Since then, dozens more studies have been conducted by Yale and other major institutions, including the National Institutes of Health, the Veterans Administration, Harvard, Johns Hopkins, Mount Sinai Medical School, Oxford University, and more. The original findings have been reconfirmed many times.

Studies to date have focused on the worst-of-the-worst cases. These are treatment-resistant patients who have suffered for years or decades, often since childhood. They have tried SSRIs, mood stabilizers, and many other medications with no success. Most have also tried standard therapies like psychological counseling or CBT, as well as alternative treatments like acupuncture, with little to no benefit. Among these extreme cases, an astonishing 70% experience rapid relief after a small IV infusion of ketamine.

If you’ve suffered for years and given up hope of ever finding relief, ketamine can sound too good to be true. But the number of patients receiving ketamine therapy (and the number of doctors who offer it) is growing rapidly. Today, more than 15 years after the breakthrough discovery at Yale, the treatment is finally starting to reach the patients who need it most.

But what does it mean when ketamine “works?” What does it feel like? Does it relieve physical symptoms, or emotional ones, or both? Will you instantly become the person you always wanted to be? Is it a permanent cure? Are there risks?

Those are big questions that can’t be answered adequately on a single web page. In the forums and throughout this site, you’ll find info about these questions from patients who have actually been there, and findings from the foremost ketamine researchers. For the remainder of this intro, we’ll stick to the most important headlines you need to get you started.

Ketamine Headlines for Newcomers

Ketamine works in a completely different way from any med you've ever taken for depression, bipolar, PTSD, or anxiety. Most medications prescribed for major depression work by manipulating the quantity of certain neurotransmitters in your brain, and their side-effects can be miserable. Ketamine works differently: it briefly blocks a certain type of receptor in the brain from being triggered. This blockade only occurs during the treatment, while you are actually connected to the IV. Afterwards, the Most medications prescribed for major depression work by manipulating the quantity of certain neurotransmitters in your brain, and their side-effects can be miserable. Ketamine works differently: it briefly blocks a certain type of receptor in the brain from being triggered. This blockade only occurs during the treatment, while you are actually connected to the IV. Afterwards, the acute effects of the infusion dissipate within minutes, and any lingering side-effects like fatigue rarely last more than a few hours.

We don’t completely understand yet exactly how ketamine relieves symptoms, but we have a pretty good idea. When ketamine is administered via slow infusion, unique conditions are created in the brain which trigger a delicate cascade of events. This cascade affects certain receptors and signalling pathways, and produces a protein that triggers rapid growth of neural connections. Researchers suspect this “rewiring” is part of the antidepressant effect. Ketamine is also a powerful anti-inflammatory agent, and since depression is highly correlated with chronic inflammation, this may also be part of the antidepressant effect. There may well be other factors that haven’t been identified yet. When ketamine is administered via slow infusion, unique conditions are created in the brain which trigger a delicate cascade of events. This cascade affects certain receptors and signalling pathways, and produces a protein that triggers rapid growth of neural connections. Researchers suspect this “rewiring” is part of the antidepressant effect. Ketamine is also a powerful anti-inflammatory agent, and since depression is highly correlated with chronic inflammation, this may also be part of the antidepressant effect. There may well be other factors that haven’t been identified yet.

Ketamine is not a one-time, permanent cure but it has the potential for lasting relief. For most patients who respond to ketamine, the symptomatic relief will begin to diminish eventually. Duration varies from patient to patient. In general, a series of multiple infusions provides longer lasting relief than a single infusion, and younger patients tend to get longer relief than older ones. For patients who relapse, getting additional infusions can often restore the relief. Only a few hundred patients so far have been treated longer than one year, which is a tiny fraction of the the world’s 350 million sufferers, and we don’t yet know if the infusions can be repeated indefinitely with sustained effect. For most patients who respond to ketamine, the symptomatic relief will begin to diminish eventually. Duration varies from patient to patient. In general, a series of multiple infusions provides longer lasting relief than a single infusion, and younger patients tend to get longer relief than older ones. For patients who relapse, getting additional infusions can often restore the relief. Only a few hundred patients so far have been treated longer than one year, which is a tiny fraction of the the world’s 350 million sufferers, and we don’t yet know if the infusions can be repeated indefinitely with sustained effect. Many patients find that during the initial period of relief they are suddenly able to break out of persistant negative behaviors and thought loops, and achieve massive emotional healing rapidly, so that even if the physical symptoms of depression return they are much better able to handle it than before – even if they don’t get ongoing infusions. This period can enable them to make lasting behavioral changes that were previously impossible, and to get real value out of talk therapy even after years of futility.

The antidepressant effect depends on administering the ketamine in a unique and precise way. The The route of administration (ROA) is extremely important. The delicate cascade of events described above is triggered only when precise conditions are created in the brain. A slow IV infusion creates these conditions. It allows the ketamine to travel directly to the brain at a controlled rate, without being metabolized by the internal organs. Other ROAs – nasal, oral, injection – cannot deliver ketamine to the brain in this manner. They may help some patients, but IV infusion is the gold standard of ketamine therapy, and is used in virtually all the published studies.

Ketamine therapy is not covered by insurance. In the US, the infusion fee charged by most ketamine doctors is a In the US, the infusion fee charged by most ketamine doctors is a few hundred dollars . This is consistent with similar procedures that involve an IV drip, monitoring of vitals, etc. Examples are hemodialysis, chemotherapy, or infusions for rheumatologic disorders. Insurance covers most of the cost of those other procedures. But ketamine patients must bear the full cost out-of-pocket, which makes it far too expensive for many who need it. Many lifelong sufferers are unemployed or underemployed, and simply can’t afford the treatment. The lack of insurance coverage is the single greatest obstacle preventing widespread adoption.

Ketamine is not FDA approved for treatment of depression. This is the reason insurance won't cover it. Ketamine has been FDA approved as an anesthetic for 50 years and is used in virtually every operating room in the world. It’s on the World Health Organization’s Ketamine has been FDA approved as an anesthetic for 50 years and is used in virtually every operating room in the world. It’s on the World Health Organization’s List of Essential Medicines , and doctors around the world have extensive clinical experience with it. But today’s FDA is designed to approve brand new drugs, not to re-examine old ones. So getting an old drug approved for a new use is virtually impossible because the FDA requires extensive trials, and they are enormously expensive to conduct. Pharmaceutical companies make this investment for new, patented drugs in order to turn them into moneymakers that will recover the cost of the trials, and then some. But ketamine’s patent expired long ago. It is inexpensive to manufacture and is sold generically. As a result, pharmaceutical companies could not earn much profit from ketamine even if demand were to soar. Although ketamine can relieve immense human suffering, no one is interested in footing the bill to conduct FDA trials. Luckily, doctors in the U.S. are permitted to use it off label.