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

September 5, 2022

Authors: C Sophia Albott, Kelvin O Lim, Christopher Erbes, Paul Thuras, Joseph Wels, Susanna J Tye, Paulo R Shiroma

Journal: Journal of Affective Disorders

DOI: 10.1016/j.jad.2022.04.066

Year Published: 2022


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.


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.


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.


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


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.

Back to Publications