Ketamine and esketamine (Spravato) overview

 

Ketamine was developed several decades ago as an anesthesia drug, but it was found in 2006 to provide quick relief from depression symptoms for treatment-resistant patients.  Since then, many other studies have continued to show the same type of result - ketamine provides quick improvement in depression.

Ketamine, which works about 65% of the time for treatment-resistant depression, is different from other medications because it targets the glutamate neurotransmitter system, while typical antidepressants affect serotonin, norepinephrine, or dopamine.  Ketamine also works faster than other medications - many people get better after just one treatment. Other antidepressants usually take a few weeks to start working, so you can see the advantage.  Another important difference is that ketamine is especially good at stopping suicidal thoughts, which is critically important where safety is concerned.

Esketamine became available in 2019.  While ketamine is usually given as an IV infusion, esketamine (Spravato) is a nasal spray, which is much easier to administer.  It is chemically related to ketamine, a mixture of the two chemical isomers S-ketamine and R-ketamine.  Esketamine, or Spravato, is actually the one isomer isolated from the ketamine mixture, S-ketamine, which is thought to be the more effective of the two isomers.

 

Both of these medicines are important options for treatment-resistant depression, which is usually defined as a depression that has not responded to 2 or more antidepressants.  Overall, depression creates an enormous burden on individuals and on society as a whole.  A 2018 study found a 10% one-year and 21% lifetime prevalence of Major Depressive Disorder, which is just one of the different types of depression (Hasin DS, JAMA Psychiatry. 2018 Apr 1;75(4):336-346).  Another past study, known as the STAR*D trial, showed that over 30% of patients do not respond to a traditional antidepressant.  After failing 2 antidepressants, and chances of success with a 3rd or 4th medication go down dramatically.

 

Now people can choose from ketamine or esketamine (Spravato), two treatments that provide more rapid results for many of those suffering from treatment-resistant depression.  And while they are not effective for everyone, we are fortunate to have these options that do work so much of the time.