Source: The Mount Sinai Hospital
For the current study, participants were randomly assigned to receive six infusions of ketamine, administered three times per week over two consecutive weeks, compared to six infusions of the psychoactive placebo control midazolam (chosen because its pharmacokinetic parameters and nonspecific behavioral effects are similar to those of ketamine) administered and evaluated over the same schedule. Individuals in this study had severe and chronic PTSD from civilian or military trauma, with median duration of 14 years and nearly half of the sample taking concomitant psychotropic medications. The primary traumas reported by participants 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. All study participants were assessed at baseline, at week 1 and week 2, as well as on each infusion day by teams of trained study raters who administered the Clinician Administered PTSD Scale for DSM-5 and the Montgomery-Asberg Depression Rating Scale (MADRS), standard rating scales for the assessment of PTSD and depression.
Significantly more participants in the ketamine group (67 percent) attained at least 30 percent or more reduction in symptoms from baseline at week two than those in the midazolam group (20 percent). Furthermore, ketamine infusions were associated with marked improvements across three of the four PTSD symptom clusters — intrusions, avoidance, and negative alterations in cognitions and mood. In the subsample of ketamine responders, improvement in PTSD symptoms was rapid, observed 24 hours after the first infusion, and was maintained for a median of 27.5 days following the primary outcome assessment day. In addition to PTSD symptom improvement, the ketamine group exhibited markedly greater reduction in comorbid depressive symptoms than the midazolam group, which is notable given the high comorbidity of depression in individuals with PTSD. Study findings further suggested that repeated ketamine infusions are safe and generally well-tolerated in individuals with chronic PTSD.