Safe, effective
Results showed significantly lower total CAPS-5 scores for the ketamine group vs. the midazolam group at week 1 (score difference, 8.8 points; P = .03) and at week 2 (score difference, 11.88 points; P = .004).
Those receiving ketamine also showed improvements in three of the four PTSD symptom clusters on the CAPS-5: avoidance (P < .0001), negative mood and cognitions (P = .02), and intrusions (P = .03). The fourth symptom cluster – arousal and reactivity – did not show a significant improvement.
In addition, the ketamine group showed significantly greater improvement scores on the MADRS at both week 1 and week 2.
Treatment response at 2 weeks was achieved by 10 members of the ketamine group and by three members of the midazolam group (P = .03).
Secondary analyses showed rapid improvement in the treatment responders within the ketamine group, with a mean change of 26 points on the total IES-R score between baseline and 24 hours after their first infusion, and a mean change of 13.4 points on the MADRS total past-24-hour score, a 53% improvement on average.
“A response at 2 weeks is very rapid but they got better sometimes within the first day,” Dr. Feder noted.
There were no serious AEs reported. Although some dissociative symptoms occurred during ketamine infusions, with the highest levels reported at the end of the infusion, these symptoms had resolved by the next assessment, conducted 2 hours after infusion.
The most frequently reported AE in the ketamine group, compared with midazolam, after the start of infusions was blurred vision (53% vs. 0%), followed by dizziness (33% vs. 13%), fatigue (33% vs. 87%), headache (27% vs. 13%), and nausea or vomiting (20% vs. 7%).
‘Large-magnitude improvement’
The overall findings show that, in this patient population, “repeated intravenous ketamine infusions administered over 2 weeks were associated with a large-magnitude, clinically significant improvement in PTSD symptoms,” the investigators write.
The results “were very satisfying,” added Dr. Feder. “It was heartening also to hear what some of the participants would say. Some told us about how their symptoms and feelings had changed during the course of treatment with ketamine, where they felt stronger and better able to cope with their trauma and memories.”
She noted, however, that this was not a study designed to specifically assess ketamine in treatment-resistant PTSD. “Some patients had had multiple treatments before that hadn’t worked, while others had not received treatment before. Efficacy for treatment-resistant PTSD is an important question for future research,” Dr. Feder said.
Other areas worth future exploration include treatment efficacy in patients with different types of trauma and whether outcomes can last longer in patients receiving ketamine plus psychotherapy treatment, she noted.
“I don’t want to ignore the fact that currently available treatments work for a number of people with chronic PTSD. But because there are many more for whom [the treatments] don’t work, or they’re insufficiently helped by those treatments, this is certainly one potentially very promising approach that can be added” to a clinician’s toolbox, Dr. Feder said.
Speaks to clinical utility
Commenting for this news organization, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University, New Haven, Connecticut, called this a “very solid and well-designed” study.
“It definitely builds on what’s been found in the past, but it’s a critical piece of information speaking to the clinical utility of this treatment for PTSD,” said Dr. Sanacora, who is also director of the Yale Depression Research Program and was not involved with the current research.
He agreed with the investigators that PTSD has long been a condition that is difficult to treat.
“It’s an area that has a great unmet need for treatment options. Beyond that, as ketamine is becoming more widely used, there’s increasing demand for off-label uses. This [study] actually provides some evidence that there may be efficacy there,” Dr. Sanacora said.
Although he cautioned that this was a small study, and thus further research with a larger patient population will be needed, it provides a compelling foundation to build upon.
“This study provides clear evidence to support a larger study to really give a definitive statement on the efficacy and safety of its use for PTSD. I don’t think this is the study that provides that definitive evidence, but it is a very strong indication, and it very strongly supports the initiation of a large study to address that,” said Dr. Sanacora.
He noted that, although he’s used the term “cautious optimism” for studies in the past, he has “real optimism” that ketamine will be effective for PTSD based on the results of this current study.
“We still need some more data to really convince us of that before we can say with any clear statement that it is effective and safe, but I’m very optimistic,” Dr. Sanacora concluded.
The study was funded by the Brain and Behavior Research Foundation, Mount Sinai Innovation Partners and the Mount Sinai i3 Accelerator, Gerald and Glenda Greenwald, and the Ehrenkranz Laboratory for Human Resilience. Dr. Feder is a coinventor on issued patents for the use of ketamine as therapy for PTSD. A list of all disclosures for the other study authors are listed in the original article.
A version of this article first appeared on Medscape.com.