Low-Dose Ketamine Benefits Cognitive Function in Treatment-Resistant Depression

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Ketamine also had beneficial effects on cognitive function in relation to its antidepressant effect.

A low dose of ketamine infusion can provide a rapid and sustained antidepressant effect in patients with treatment-resistant depression, according to a study published in the Journal of Affective Disorders. In addition, a subanesthetic dose of ketamine was shown to improve functional impairment traditionally associated with treatment-resistant depression.

This randomized, double-blind, placebo-controlled study included 71 adults aged 21 to 65, diagnosed with major depressive disorder according to the DMS-IV, and who additionally met criteria of treatment-resistant depression. Patients with major comorbidities or a history of alcohol or drug abuse were excluded. Participants were randomly assigned into a group receiving ketamine 0.5 mg/kg, ketamine 0.2 mg/kg, or normal saline placebo infusions. The Hamilton Depression Rating Scale was used to assess the participants’ depressive symptoms at baseline and at different time points following infusion; cognitive function was evaluated by testing the participants’ working memory and go/no-go tasks at baseline, day 3, and day 14 post treatment.

Study results showed that depressive symptoms improved across different time periods among patients with treatment-resistant depression receiving either ketamine infusion (0.5 or 0.2 mg/kg) or placebo. Paired t tests were used to stratify results by treatment group and treatment response, and they revealed that correct responses in the go/no-go task significantly increased from baseline to day 14 in the 0.5 mg/kg ketamine infusion group. After adjusting for age, gender, and education, a significant association was also observed between depressive symptoms and changes in cognitive function at day 3 in the 0.5 mg/kg infusion group.

A limitation of the study was the add-on design, in which normal medications taken by the participants were not discontinued during the ketamine treatment and evaluation; therefore, the findings are more appropriately explained as an add-on effect of low-dose ketamine infusion. The study was also limited by testing only working memory and go/no-go tasks in assessing cognitive function; it did not test episodic and autobiographical memory. Furthermore, researchers did not arrange post-ketamine infusion assessments for Day 2 to avoid a potential learning effect attributed to the cognitive tasks.

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The study findings indicated that a single low dose of ketamine infusion did not impair cognitive function of patients with treatment-resistant disorder; rather, patients in the 0.5 mg/kg ketamine infusion group demonstrated specific cognitive improvement measured by the go/no-go task. Although this study showed that ketamine had beneficial effects on cognitive function in relation to its antidepressant effect, further studies are needed to understand the effects of repeated ketamine infusions on cognitive function.


Chen MH, Li CT, Lin WC, et al. Cognitive function of patients with treatment-resistant depression after a single low dose of ketamine infusionJ Affect Disord. 2018; 241:1-7.