Does Ketamine Therapy for Anxiety Help?

About the Author Dr. Steven P. Levine is a board-certified psychiatrist internationally recognized for his contributions to advancements in mental health care. Though he is a psychiatrist who places great emphasis on the importance of psychotherapy, medication is often a necessary component of treatment, and he was dissatisfied with the relatively ineffective available options with burdensome side effects. Dr. Levine pioneered a protocol for the clinical use of ketamine infusions, has directly supervised many thousands of infusions and has helped establish similar programs across the country and around the world.

Ketamine is becoming widely accepted as a treatment for depression and is increasingly being used for other psychiatric disorders as well. Furthermore, it can lead to an immediate and robust response that has led a prominent research psychiatrist from Mt. Sinai, Dr. Murrough, to say “it blew the doors off what we thought we knew about depression treatment”. Sustained improvement in psychiatric symptomatology likely has to do with Ketamine’s mechanism of action which helps connect brain cells. In this blog, we will specifically examine the mechanisms underlying the efficacy of ketamine for anxiety as well as other mood disorders. 

Many are aware of Ketamine’s notorious use as a “club drug”. This is an unfortunate stigma for the drug because at safe doses, administered intravenously by a psychiatrist, antidepressant effects extend longer than just another “feel good” drug. In fact, this is a key distinction between many drugs of abuse and Ketamine. Ketamine is not an antidepressant because it can cause feelings of pleasure when administered. Rather, it is an antidepressant because of what happens after such side effects go away.

Ketamine for Anxiety – A Case Study

To demonstrate this idea, a 2013 study by Murrough JW et al.compared Ketamine with a drug called midazolam, which is a drug that produces an immediate “feel good” effect similar to alcohol. What researchers found is that patients who received a Ketamine infusion responded 2x more than those who received midazolam. Not only was the response greater, but the Ketamine-treated patients maintained the relative 2x response over one week after only one infusion, whereas the other patients did not. You might think that this is just repeating what we already know about Ketamine : it works, but what makes this study especially significant it that it compares Ketamine to an active intravenous placebo in what is called a randomized-controlled trial, essentially the gold standard of drug trials. Previous studies either didn’t have a comparison or had an inactive placebo, such as a sugar pill taken by mouth.

Most of the patients in the above study saw an antidepressant effect within 24 hours and an antidepressant effect was sustained for longer than the drug actually stays in the body, which is no longer than a day after the infusion. This type of response is unusual in the mental health community. We usually see that an antidepressant takes weeks if not months to achieve an antidepressant response and it does not maintain its effect unless it is taken every day.

As it turns out, Ketamine is fat soluble and this makes it efficient at penetrating the brain. Ketamine can enter the brain and reach the regions of the brain that exert an antidepressant response at a very fast rate. Two brain regions that may help Ketamine exert its antidepressant response are the hippocampus (a part of the brain responsible for short-term memory) and the prefrontal cortex or the part of the brain you “work-out” when you go to see a therapist.

Traditional antidepressants, like SSRIs, work by increasing the amount of serotonin available in your brain ㄧ this is based on the well-established theory that depression is precipitated by deficiencies in brain chemicals called neurotransmitters. However, there is more to depression than merely a “chemical imbalance” and perhaps you have suspected this after finding that SSRIs failed to adequately treat your depression. This is where Ketamine for anxiety comes in since it works at the synaptic level and actually increases the number of connections in the brain, thereby modulating transmission of nerve signals in certain parts of the brain. In a 2010 study, Li N et al. demonstrated that the very brain cells that produce serotonin and other neurotransmitters develop new synapse connections within 24 hours after Ketamine infusion. This was seen not only by looking through a microscope, but also by measuring the amount of proteins that help to build these synapse connections. The ability to change or build new synapse connections between brain cells is called neuroplasticity and this is a process that Ketamine can facilitate.

Often times the terms glutamate and NMDA come up when talking about Ketamine. Glutamate is a brain neurotransmitter and NMDA is a neurotransmitter “receptor”. If glutamate and NMDA were a key and ignition respectively, glutamate may be the “key to the ignition” that starts the process of synapse formation as mentioned above.

So now that we have one idea of how Ketamine exerts its antidepressant effect, how is it that the response stays around for days without actively taking the drug everyday? Although scientists are searching for this answer, Ketamine can clearly change not only neurotransmitter release but also brain cell synapse connections when viewed through a microscope. One hypothesis is that it is easier for the body to maintain new synapses that are actively used rather than the very neurotransmitters that are transmitted between the synapses. However, it has become abundantly clear that the use of ketamine for anxiety is not only safe, but is an ethical responsibility for treatment providers.

We must continue to remind ourselves that the brain is a structure that can be changed. Some patients find it easier to change certain maladaptive behaviors after Ketamine treatment and this may be possible because the newly formed synapses help support healthy behaviors. When we view Ketamine in this light, it becomes all the more important to maintain or start positive behaviors/habits after Ketamine treatment so that the positive effects of Ketamine are used and maintained.