PTSD Augmented Psychotherapy With Ketamine (KPE) - First Results

Background
Augmenting prolonged exposure (PE) with pharmacotherapy has been suggested as a promising solution to address treatment-resistant PTSD and high dropout rates. Ketamine has been shown to have rapid-acting effects on treatment resistant depression following single infusion and with neurogenesis, that may promote new learning. We present first results of ketamine augmentation of intensive 7-day-PE (KPE) for PTSD patients.
Methods
17 PTSD patients were randomized to Ketamine or Midazolam groups, after undergoing medical and clinical evaluation. The treatment protocol consisted of 7 daily sessions of PE with one-time 40min infusion of 0.5mg/kg ketamine or midazolam following the first exposure session inside an MRI. Before, after and follow-up treatment measurements included behavioral and fMRI data.
Results
PTSD symptoms scores were significantly reduced in both groups at 30-days follow-up [F(1,13)=7.47, pResting-state MRI before and after infusion indicated connectivity between caudate and parieto-occipital were significantly higher in the ketamine group [t(13)=5.74, pKetamine group showed higher global brain connectivity in tempo-occipital clusters at the end of treatment (7 days after first scan). A negative correlation between default mode network connectivity and PCL5 scores at follow up was found [r=-0.57, t(10)=-2.2, p=0.051)].
Conclusions
Augmenting PE with ketamine is a novel treatment. This study shows promising results in behavioral and neural measures, suggesting higher efficacy for KPE in long-term outcomes. The low number of patients requires us to use these results with caution, but evidence supporting changes in brain connectivity and no drop out propel further investigation.