Repeated intravenous (IV) ketamine infusions may significantly reduce the severity of symptoms in individuals with chronic post-traumatic stress disorder (PTSD).
A study published in the American Journal of Psychiatry found the treatment displayed rapid symptom improvements and was generally safe and well-tolerated by patients with chronic PTSD. It is the first randomized controlled trial of repeated ketamine administration for chronic PTSD.
Previously, researchers from the Icahn School of Medicine at Mount Sinai, New York, New York, conducted a controlled trial of a single dose of IV ketamine for PTSD, which showed significant and rapid symptom reduction 24-hours post-infusion. Researchers observed the same rapid symptom reduction in the current study, and it was maintained for a median of 27.5 days following the primary outcome assessment day.
"The data presented in our current study not only replicate, but also builds on our initial findings about ketamine for PTSD, indicating that in addition to being rapid, ketamine’s effect can be maintained over several weeks,” Dennis S. Charney, MD, and colleagues said. “PTSD is an extremely debilitating condition and we are pleased that our discovery may lead to a treatment option for so many who are in need of relief from their suffering.
Study participants were randomly assigned to receive 6 infusions of ketamine, administered 3 times per week over 2 consecutive weeks. The control group received 6 infusions of the psychoactive placebo control midazolam administered and evaluated over the same schedule. Researchers chose to use midazolam in the placebo group because its pharmacokinetic parameters and nonspecific behavioral effects are similar to those of ketamine.
Of the ketamine group participants, 67% attained at least a 30% reduction in symptoms from baseline at week 2, compared with 20% in the midazolam group. Three of the four PTSD symptom clusters — intrusions, avoidance, and negative alterations in cognitions and mood — displayed marked improvements and were associated with the ketamine infusions. Compared to the midazolam group, the ketamine group also exhibited a more significant reduction in comorbid depressive symptoms.
Participants in the study had severe and chronic PTSD from civilian or military trauma, with a median duration of 14 years. The primary traumas reported included sexual assault of molestation, physical assault or abuse, witnessing violent assault or death, having survived or responded to the 9/11 attacks, and combat exposure.
“Future studies may include administering additional doses over time and examining repeated ketamine infusions combined with trauma-focused psychotherapy, to help us determine how we can maintain this robust response over the long term,” lead author Adriana Feder, MD, said, “We want people suffering with PTSD to know that hope is on the horizon and we are working diligently to collect the information that will help bring them the relief they so desperately need.”
Feder A, Costi S, Rutter S, et al. A randomized controlled trial of repeated ketamine administration for chronic posttraumatic stress disorder. The American Journal of Psychiatry: 2021 January 5; [Epub ahead of print.].