Acute cognitive effects of single-dose intravenous ketamine in major depressive and posttraumatic stress disorder

Abstract

Intravenous (IV) subanesthetic doses of ketamine have been shown to reduce psychiatric distress in both major depressive (MDD) and posttraumatic stress disorder (PTSD). However, the effect of ketamine on cognitive function in these disorders is not well understood. To address this gap, we examined the effect of a single dose of IV ketamine on cognition in individuals with MDD and/or PTSD relative to healthy controls (HC). Psychiatric (n = 29; 15 PTSD, 14 MDD) and sex- age- and IQ matched HC (n = 29) groups were recruited from the community. A single subanesthetic dose of IV ketamine was administered. Mood and cognitive measures were collected prior to, 2 h and 1 day post-ketamine administration. MDD/PTSD individuals evidenced a large-magnitude improvement in severity of depressive symptoms at both 2-hours and 1 day post-ketamine administration (p's < .001, Cohen d's = 0.80-1.02). Controlling for baseline performance and years of education, IV ketamine induced declines in attention (ATTN), executive function (EF), and verbal memory (VM) 2 h post-administration, all of which had resolved by 1 day post-ketamine across groups. The magnitude of cognitive decline was significantly larger in MDD/PTSD relative to HC on attention only (p = .012, d = 0.56). Ketamine did not affect working memory (WM) performance. Cognitive function (baseline, change from baseline to post-ketamine) was not associated with antidepressant response to ketamine. Results suggest that while ketamine may have an acute deleterious effect on some cognitive domains in both MDD/PTSD and HC individuals, most notably attention, this reduction is transient and there is no evidence of ketamine-related cognitive dysfunction at 1 day post-administration.

Fig. 1. Mean depression symptom severity scores (self-reported on the Beck Depression Inventory II) across timepoints in healthy control participants (HC) and participants with major depressive disorder (MDD) and posttraumatic stress disorder (PTSD).

Error bars indicate 95% confidence intervals. Dotted lines separate categories of depression symptom severity. BDI-II Beck Depression Inventory II.

Fig. 2. Mean and 95% confidence intervals for normalized Cogstate scores/composite scores across the three study timepoints: pre-ketamine (prior to ketamine administration); 2 h post-ketamine; 24 h post-ketamine administration across groups.

HC healthy control, MDD major depressive disorder, PTSD posttraumatic stress disorder, IDN identification task, DET detection task, OCL one card learning task, ONB, one-back task, GML Groton maze learning test, ISL International Shopping List. *p < .01.

Fig. 3. Mean and SD for change scores at each timepoint relative to baseline for each Cogstate score/composite score.

HC healthy control, MDD major depressive disorder, PTSD posttraumatic stress disorder, ATTN attention composite score, WM working memory composite score, EF executive functioning, VM verbal memory. *p < .01.