Ketamine Treatment and Depression

What is Ketamine?

Ketamine is an anesthetic that has been safely used in both humans and animals since the 70’s.  It was then approved by the FDA for use on soldiers during the Vietnam War.  It proved to be a useful anesthetic in the battle field because it was fast acting and provided hemodynamic stability, which was of paramount importance for the wounded.  Ketamine was first used as a general anesthetic, which is still used today.

Over the last decade, ketamine has been used in non-traditional ways; most impressive of all is its ability to act as an efficacious, rapid-acting medication against depression and other mood disorders.  Several prominent institutions including Yale University, Cleveland Clinic, Mayo Clinic, NYU, Massachusetts General Hospital, the Black Dog Institute, and the National Institute of Mental Health have conducted their own clinical trials, and have shown up to a 70% response rate to ketamine as an antidepressant.


How does it work?

Depression causes a disruption of neuronal connections in the cortical and limbic regions of the brain which control cognition, mood, and emotion.  When we experience persistent high levels of social, environmental, and work-related stresses, the neuronal connections in our brain, called synapses, dwindle and atrophy.  This, in turn, affects how we think, and our motivation and emotion.  The longer we experience these stressors, the more connections we lose; and, the more severe the neuronal atrophy.

In contrast to the effects of stress and depression, chronic treatment of antidepressants produce a slow increase in neuroplasticity, and allows for the neural connections to reform.  The response rate to a first line antidepressant, however, is less than 50% and takes weeks to months to start taking effect.

As an NMDA receptor blocker, Ketamine works by a different mechanism. It causes a surge in glutatamate,  a major excitatory neurotransmitter in the brain.  Through an elaborate pathway,  there is a subsequent increase in BDNF (Brain-Derived Neurotrophic Factor), a neurotrophin that promotes neuronal growth and connections in the brain.  A single infusion of ketamine alleviates depressive symptoms within hours in patients who have failed to respond to conventional antidepressants.  It is therefore very effective in significantly decreasing suicidal ideations.  Ketamine rapidly reestablishes the neuronal connections in the brain that were once lost due to chronic persistent depression.

The fast and efficacious mechanism by which ketamine treats symptomatology is an exciting new advancement in the management of depression.


Route of Administration?

While there are other administrations available, intravenous infusions are absorbed more easily by the body in comparison to other routes. Plus, an IV administration allows a much more accurate dosage based on body weight. Overall, the precision and effectiveness of IV administration makes it the top choice of most professionals.

The effectiveness of how ketamine impacts the body centers largely on how it is administered. Bioavailability refers to the portion of the drug that circulates the body once it enters it. Check out the bioavailability of three of the main options for administration.

The fast and efficacious mechanism by which ketamine treats symptomatology is an exciting new advancement in the management of depression.


IV Administration 100% Ketamine Bioavailability

The only way to ensure that an individual’s body is getting an exact dose of ketamine is to administer it through an IV. This is the most controlled method that ensures that the patient’s body is getting the specific dose that their condition requires. Ketamine used as a general anesthetic is designed to be given in this method so it only makes sense that it would work well being administered through an IV for infusion therapy. This process takes out the guess-work and can get proper dosage down to the milligram based on the patient’s weight and height.

Intramuscular Administration ~93% Ketamine Bioavailability

Some doctors offer intramuscular administration. The issue here is that this method often leads to uneven absorption which could cause prolonged side effects. This could make it vir-tually impossible for a doctor to identify if ketamine infusion therapy is even effective on their patient.

Intranasal Administration ~45% Ketamine Bioavailability

Another method that is sometimes used is intranasal administration. That is, a mist is shot up through the nasal passage. The issue with this method is that it has to overcome a number of barriers before it reaches the body’s bloodstream. The chance of the mist being evenly ad-ministered through the nasal passage is incredibly unlikely. However, even if that was accom-plished, patients could possibly sneeze it out, or the ketamine could run into a mucus barrier in the nasal cavity before it even has the opportunity to enter the bloodstream. There are a number of variables that could impact the effectiveness of the dose.



IV administration is the most efficient way for the body to receive ketamine infusion therapy. Not only can the dosage be better controlled, but the body will have 100% access to the dose at the most precise rate. Individuals who are considering ketamine to treat depression should ask their doctor which method they use for administration. Keep in mind; the answer could severely influence the outcome of your treatment.


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