Ketamine and Esketamine (Spravato) For PTSD
Posttraumatic stress disorder (PTSD) is a condition for which treatment with the anesthetic drug ketamine is sometimes considered. This article explains what PTSD is and discusses the possible role of ketamine in its management.
What is PTSD?
PTSD is an illness that develops in some people who experience or witness a terrifying and potentially life-threatening event. Examples of such traumatic events are military combat, fires, traffic accidents, and rape; serious medical events may also result in PTSD. Persons with PTSD uncontrollably re-experience the traumatic event in flashbacks and nightmares. They have high anxiety levels and other forms of emotional disturbance. They avoid thoughts and situations that remind them of the event. They have disturbances of thinking and behavior. Other symptoms can also be present. The illness lasts for months to years and can be difficult to successfully treat.
How common is PTSD?
About 8% of the American population may expect to suffer from PTSD at some time during their lives. The risk is higher in people, such as soldiers, who are more likely to be exposed to danger. The risk is lower, such as 1-3%, in some other parts of the world.
Treatment of PTSD
PTSD is most commonly treated using antidepressant drugs such as sertraline and paroxetine. However, only about 50-60% of patients improve and fewer than a quarter of patients recover completely with treatment. A small proportion of patients continues to remain severely ill for years.
Some patients with PTSD may be severely impaired by their symptoms and unable to function meaningfully in everyday life. Some may experience severe emotional and behavioral disturbances that can range from aggression and violence to suicidality. Effective treatments are needed for such patients. The anesthetic drug ketamine, administered in doses much lower than those used for anesthesia, may be of unique value in such patients with PTSD.
Ketamine for PTSD
There have been many individual reports in the medical literature of patients improving with intravenous ketamine treatment. In an important study conducted at Mount Sinai in New York a few years ago, researchers identified 41 patients with severe, longstanding PTSD. These patients were randomly assigned to receive a single session of treatment with either ketamine or a sedating drug, midazolam. Two weeks later, patients who received ketamine were treated with midazolam and vice versa. Neither patients nor those who assessed the treatment benefits knew who received which drug and when; therefore, the benefits of the two drugs could be validly compared without risk of bias by preconceived expectations. Ketamine was administered by intravenous infusion across 40 minutes.
In both phases of the study, ketamine was associated with substantial reduction in PTSD symptom severity. The benefit with ketamine was significantly greater than that with the comparison drug, midazolam. The benefit was most prominent one day after the treatment and, in about a third of patients, persisted for at least two weeks.
Ketamine also had an antidepressant effect, and this also was seen most strongly after one day. Ketamine-related improvement in PTSD was independent of ketamine-esketamine-related improvement in depression.
Whereas patients experienced minor side effects with ketamine, these were mostly brief and were no longer present four hours after ketamine administration. There were no serious side effects associated with ketamine. Similar controlled studies have confirmed this effect.
Take home message
Low dose (0.5 mg/kg), intravenous ketamine infusion may be a useful treatment for patients with severe, longstanding PTSD. An advantage of ketamine is that the benefits are substantial and are obtained within just one day of treatment. A further advantage is that accompanying depressive symptoms are also improved within a day of receiving ketamine. Thus, ketamine may be useful in PTSD patients who do not respond to oral medicines, and in those who require an emergency intervention for distressing and disabling symptoms.