Repeated ketamine infusions may lead to rapid symptom improvement in people with chronic posttraumatic stress disorder (PTSD), suggests a study in AJP in Advance. Participants who received six ketamine infusions over a two-week period experienced greater drops in PTSD symptoms and comorbid depressive symptoms compared with participants who received the sedative midazolam.

The findings are “an important next step in our quest to develop novel pharmacologic interventions for this chronic and disabling disorder, as a large number of individuals are not sufficiently helped by currently available treatments,” said lead author Adriana Feder, M.D., of the Icahn School of Medicine at Mount Sinai in a press release.

The study involved patients aged 18 to 70 with a primary diagnosis of PTSD who had been experiencing symptoms for at least three months and had a score of ≥30 on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), indicating symptoms of at least moderate severity. In total, 30 patients were randomly assigned to receive six infusions of either IV ketamine or midazolam (psychoactive placebo control) approximately three times a week for two weeks.

The researchers evaluated the study participants using several measures, including the CAPS-5 and the Montgomery-Åsberg Depression Rating Scale (MADRS), before the first infusion and following the first and second week of infusions. On infusion days, the researchers also evaluated the study participants for potential side effects (including dissociative and manic symptoms) before and following the infusion.

The ketamine group showed a significantly greater improvement in CAPS-5 and MADRS total scores than the midazolam group from baseline to week 2, Feder and colleagues reported. Additionally, significantly more participants in the ketamine group (67%) experienced a ≥30% reduction in symptoms from baseline compared with those in the midazolam group (20%).

“Ketamine infusions were associated with marked improvements across three of the four PTSD symptom clusters: intrusions, avoidance, and negative alterations in cognitions and mood,” the authors wrote. “In the subsample of ketamine responders, improvement in PTSD symptoms was rapid, observed 24 hours after the first infusion, and maintained for a median of 27.5 days after the primary outcome assessment day.”

The most frequently reported side effects by the ketamine group included blurred vision, dizziness, fatigue, and headache. Although some dissociative symptoms emerged during ketamine infusions, these symptoms tended to resolve within two hours.

“The study findings suggest the overall safety and tolerability of repeated ketamine infusions in this patient population. Further research is needed to evaluate the efficacy of novel interventions to prevent PTSD symptom relapse over time, including clinical trials to evaluate the safety, tolerability, and efficacy of periodic intravenous ketamine (or intranasal esketamine) administration as maintenance over several months … and studies examining whether combining repeated ketamine administration with evidence-based psychotherapy for PTSD can help reduce the likelihood of relapse after cessation of ketamine infusions,” the authors concluded.

For related information, see the American Journal of Psychiatry article “Psychedelics and Psychedelic-Assisted Psychotherapy.”

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