Ketamine for Treatment Resistant Depression


Globally, approximately more than 350-million people of all ages suffer from some form of depression. It is a world-wide epidemic that constitutes the leading global cause of disability. It is also one of the primary contributors to the overall global burden of disease. In its worst form, depression can lead to its most fatal expression – suicide.

A number that appears to be increasing daily, approximately one-third of patients with major depressive disorder (MDD) do not respond to existing antidepressants. Their depression is treatment-resistant depression or TRD. Those who do respond to pre-existing antidepressants generally take weeks or even months to achieve any significant results. The necessity for rapidly-acting and more efficacious treatments has never been more clear.

What Is Ketamine?

There is a growing amount of evidence surrounding the efficacy of ketamine in the treatment of depression that has grown resistant to other types of treatment. But what actually is ketamine? It’s a powerful general anesthetic which stops feelings of pain, and it’s used for operations on both humans and animals. The effects don’t last long, but until they wear off, ketamine can cause a loss of feeling in the body and paralysis of the muscles. It can also lead human beings to experience a distortion in their perceived reality.

Recent studies showed that ketamine has shown significant promise as a rapidly-acting antidepressant in treatment-resistant patients with unipolar MDD. What’s more, further evidence suggests that ketamine may be efficacious also in patients with bipolar depression, post-traumatic stress disorder (PTSD), and acute suicidal ideation.

But What Does It Actually Do?

Across a range of clinical trials, as published recently in the British Medical Journal (BMJ), evidence clearly demonstrated that a single low dose (0.5mg/kg) of intravenous (KV) ketamine results in a 50-70% response rate in patients with TRD. Further research also showed that depressed patients may achieve symptom relief as early as 2 hours after a single IV shot of ketamine, and that said relief may last for up to two weeks. As previously mentioned, ketamine has also been demonstrated as efficacious in the treatment of other types of depression – namely bipolar depression, comorbid anxiety disorder, PTSD, and acute suicidal ideation. When utilizing ketamine to address the varied types of depression, it is, of course, obvious that specific considerations must be made for the conditions of administration on a case-by-case basis. For example, bipolar depression generally sees a shorter duration of the effect of ketamine, and so specific considerations must be made for the frequency of treatments in clinical practice. Nevertheless, the overall clinical findings thus far are indeed promising; very promising.



The part of the human brain that is affected by depression is called the ‘reward system’. Depression causes significant impairment to the reward system and, as demonstrated above, can cause suicidality. Given these facts, it is very likely that ketamine targets this particular neural circuit in the brain, which includes areas of the dorsal anterior cingulate cortex, orbitofrontal cortex, hippocampus, and basal ganglia. It is a major consideration that patients with severe depression, anhedonia, suicidal ideation and/or cognitive deficits have seen positive outcomes after intravenous ketamine treatments.

What The Patients Are Saying

Patients who have gone through this treatment have been generally very optimistic and positive about their treatment experiences, and word of these positive experiences is most certainly spreading fairly quickly. In a review published on, one patient said:

“You start thinking about all kinds of stuff. Whatever races through your mind—and usually when you’re depressed it’s negative sh*t—when you’re on ketamine, it’s just like: ‘Well, nothing I can do about that.’ You feel like, ‘I’m not in control, and that’s fine; you’re going to die someday and that’s just life.’ You kind of learn to just accept it, I guess.”

In another article published in 2015 by, Brent Miles, a 41-year old songwriter and journalist from Phoenix, Arizona, who suffered from bipolar depression stated:

“After my first treatment, I felt good for a week. Not the kind of bipolar ‘good’ where I’d be manic. I felt normal for the first time in a long time.”

The Pros…And The Cons

Despite all of these positive experiences, and despite the fact that ketamine has been shown to be safe and effective as an anesthetic in both children and adults at doses ranging from 1 to 3mg/kg, as well as at the subanesthetic doses of between 0.1 to 1mg/kg when treating pain and depression, there are specific side effects and, more importantly, cons, to take into account when considering Ketamine as a solution for your depression. At its subanesthetic dose level, ketamine can be associated with short-lasting neuropsychiatric effects, including neurocognitive disturbances, sensory-motor disturbances, and dissociation. On top of this, time-limited increases in the heart rate and blood pressure are also notable side effects. Up to 4 hours after the initial administration of ketamine, common adverse effects have proven to include dizziness, blurred vision, headache, nausea or vomiting, dry mouth, restlessness, and impairments in coordination and concentration.

For those of you who know ketamine’s background in the modern world, you’ll know that it has a significant history of being abused as a recreational substance. This makes the potential for abuse a very valid clinical concern and a necessary focus for research and investigation. Clearly, the lack of concrete comprehension of ketamine from this perspective reflects one solid truth. The use of ketamine for depression and alterations in mood is still a very new form of treatment. Despite there being a growing number of studies to support the theory of ketamine’s efficacy as a rapidly-acting treatment for patients with TRD, as well as those with bipolar depression, PTSD and, in some cases, those with acute SI, both clinicians and patients must be aware of the limited amount of information available thus far. Especially when addressing questions around optimal dosing and the long-term effects of ketamine treatment.

Is It Worth A ‘Shot’?

As you may clearly observe above, patients with direct experience of ketamine as treatment for their depression have had overall very positive experiences. Some mild critics may argue that other – drug-free – practices or pursuits may be a more beneficial and/or balanced approach to tackling depressive states. Practices or pursuits such as walking in nature, Yoga, swimming, dancing, or other physical endeavors. However, as a valid counter-argument, those in favour of using ketamine may argue that when experiencing deep levels of depression, one is simply unable to pull themselves together enough to partake in such activities. Ultimately, if it’s something you’re considering experimenting with, do your research and prepare yourself with as much information as possible before making your decision.'

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