Research Update: Intravenous Ketamine for PTSD
April 01, 2021
Post-traumatic Stress Disorder affects approximately 4% of Americans each year. More than 60% of people are exposed to a severe, potentially traumatic event in their lifetime. A World Health Organization study found that 2.3 % of upper-middle-income people will experience PTSD as the result of such an exposure. Traditional treatments include therapy and medication, although a substantial proportion of patients will only partially respond to traditional interventions.
Researchers at the Icahn School of Medicine recently published their work on the effectiveness of intravenous ketamine in the treatment of PTSD.
The article, entitled “A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Post-traumatic Stress Disorder” was published in the American Journal of Psychiatry in the February 2021 issue.
Individuals enrolled in the study had severe and chronic PTSD, with a median duration of 15 years. Participants were between the ages of 18 and 70. All subjects had a primary diagnosis of PTSD as defined in the DSM-5. Patients on long-term antidepressants, antipsychotics, or mood stabilizers remained on those medications during the trial.
The participants were divided in 2 groups. The ketamine group received 6 treatments of intravenous ketamine over a 2-week period. The control group received 6 treatments of midazolam over 2 weeks. All patients received continuous EKG monitoring. A physician and nurse monitored all infusions.
67% of patients receiving ketamine attained a response, defined as a 30% reduction in PTSD symptoms by the end of the 2 weeks. Among patients that responded to ketamine, the improvement was rapid, observed within 24 hours of the first infusion.
Among the ketamine responders, the improvement lasted for a median of 27 days after the 2 weeks of treatment. One patient was still feeling improvement after 50 days another patient at 102 days.
The study was stopped early due to the “robust, large magnitude and clinically significant difference” between the ketamine group and the midazolam group.
The ketamine group also exhibited a markedly greater reduction in depressive symptoms, which is important because many patients with PTSD also suffer from depression.
The ketamine treatment was safe and well-tolerated in the study population, with any side effects being minor and transient.
The authors point out that there are very few medications that are helpful in the treatment of PTSD. Only sertraline and paroxetine have FDA approval for this use. Both of these medications take months to achieve maximal effect. The lack of other medication options has made it imperative to develop new treatment options for chronic PTSD.
The mechanism of action of ketamine in patients with PTSD is not fully understood and is the subject of intense research. The authors suggest the potential mechanism may involve a rapid increase in glutamate release. Glutamate is the major excitatory neurotransmitter in the central nervous system of humans. This burst of glutamate release causes multiple downstream effects including an increase in BDNF , or brain-derived neurotrophic factor. Ketamine also causes activation of mTORC1 signaling, which leads to synaptogenesis or the formation of new connections between nerve cells in the brain.