Enhancing Trauma-Memories Reconsolidation With One-Time Ketamine Infusion

Background
NMDA receptor antagonists were found to have a vital role in extinction and reconsolidation processes. During reconsolidation, memories are activated into a labile state and can be stored in an altered form. This idea might have clinical implications in the treatment of PTSD, with current psychotherapies’ success rate rounding 50%. Here we used a single subanesthetic intravenous infusion of ketamine (NMDA receptor antagonist; 0.5mg/kg over 40min) to enhance post-retrieval extinction of real traumatic memories.
Methods
24 PTSD patients were randomized to ketamine or midazolam groups. The procedure included a one-time 40min infusion following reactivation of the traumatic memory, while in the MR scanner. This was followed by 5 prolonged exposure sessions. Brain activation during memory retrieval was assessed before and after treatment, as well as 30 and 90-days follow-up.
Results
Ketamine caused a significant decline in the amygdala and hippocampus reactivation to the traumatic event at the end of treatment, compared with the midazolam group (mean group difference amygdala=-31.78, SD=10.54, 95%CI = [-52.57, -11.48]; hippocampus = -20.12, SD=10.71, 95%CI = [-41.73, -0.07]). The ketamine group presented a decline in connectivity between amygdala and hippocampus, and hippocampus and vmPFC, compared to the midazolam group. Skin conductance response to the traumatic event was lower in the ketamine group.
Conclusions
These results suggest that one-time ketamine infusion, received after retrieval of the traumatic memory, enhances the reconsolidation process, and promotes post-retrieval extinction in humans. These findings are also presenting a proof of concept for the ability to use ketamine to augment short-term prolonged exposure for PTSD.