Neurocognitive effects of repeated ketamine infusions in comorbid posttraumatic stress disorder and major depressive disorder

This open-label study (n=15) assessed the effectiveness of six ketamine infusions (35mg/70kg) over a 12-day period on neurocognitive function in veterans with comorbid PTSD and major depressive disorder (MDD). Significant improvement was observed in working memory following completion of the infusion series while greater improvements in PTSD and MDD symptoms were associated with lower working memory, slower processing speed and faster set-shifting at baseline.

Abstract

“Background: The glutamate N-methyl-d-aspartate (NMDA) receptor antagonist ketamine rapidly ameliorates posttraumatic stress disorder (PTSD) and depression symptoms in individuals with comorbid PTSD and major depressive disorder (MDD). However, concerns over ketamine’s potential neurocognitive side effects have yet to be assessed in this population. The current study investigated 1) changes in neurocognitive performance after a repeated ketamine dosing regimen and 2) baseline neurocognitive performance as a predictor of ketamine treatment effect.

Method: Veterans with comorbid PTSD and MDD (N = 15) received six infusions of 0.5 mg/kg ketamine over a 12-day period. Neurocognitive and clinical outcomes assessments occurred at baseline and within 7 days of infusion-series completion using the CogState battery.

Results: Repeated ketamine infusions did not significantly worsen any measures of cognition. Rather, significant improvement was observed in working memory following completion of the infusion series. In addition, greater improvements in PTSD and MDD symptoms were associated with lower working memory, slower processing speed and faster set-shifting at baseline. Lower verbal learning was also predictive of improvement in depression.

Limitations: This study applied an open-label design without placebo control. As such, it is not known to what extent the correlations or improvement in neurocognitive performance may have occurred under placebo conditions.

Conclusion: This is the first study to examine the neurocognitive effects of repeated ketamine in participants with comorbid PTSD and MDD. Our findings suggest potential baseline neurocognitive predictors of ketamine response for comorbid PTSD and MDD symptoms.”

Authors: Sophia Albott, Kelvin O. Lim, Christopher Erbes, Paul Thuras, Joseph Wels, Suanna J. Tye & Paulo R. Shiroma

Summary of Neurocognitive effects of repeated ketamine infusions in comorbid PTSD and MDD

Ketamine is a high-affinity, non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist that has been used as an anaesthetic for over 40 years. It has recently been shown to have rapid-onset antidepressant effects in patients with treatment-resistant depression.

Ketamine has been shown to seriously affect neurocognition in healthy volunteers and a ketamine model of schizophrenia. However, repeated ketamine infusions may cause short- and long-term neurocognitive effects.