Comparing the Cognitive Effects of Repeated Intravenous Ketamine and Electroconvulsive Therapy in Patients With Treatment-Resistant Depression

In a multisite randomized trial comparing cognitive effects of intravenous ketamine and electroconvulsive therapy (ECT) in patients with treatment-resistant depression, those receiving six ketamine treatments showed superior cognitive functioning after a three-week treatment course compared with those receiving nine ECT sessions. No significant differences in cognitive task performance were associated with response to either treatment. Among responders followed for up to six months, no group differences emerged. Subjective memory measures were mixed: both groups improved on the Squire Memory Complaint Questionnaire, with ketamine recipients reporting greater functional gains, while ketamine-treated patients reported improvements on a global self-evaluation of memory but ECT-treated patients reported a decline. Within the ketamine group, improvements in executive functioning and cognitive flexibility survived adjustment for changes in depression, suggesting partial independence of cognitive and mood effects.

Study at a glance

Abstract

Electroconvulsive therapy (ECT) has potent antidepressant effects yet can lead to neurocognitive side effects. Ketamine is a rapid-acting antidepressant, which may be an alternative to ECT. Few have directly compared the cognitive effects of ECT and ketamine treatment. We compared cognitive effects of intravenous ketamine and ECT in patients with treatment-resistant depression (TRD), collected through a multisite, randomized trial conducted between April 2017 and November 2022 (the ELEKT-D study). Participants received 6 IV ketamine treatments or 9 ECT sessions. Cognitive functioning was assessed through 4 validated cognitive tasks at pre- and posttreatment visits. The Squire Memory Complaint Questionnaire (SMCQ) and Global Self-Evaluation of Memory (GSE-My) were used to measure changes in memory functioning. Responders (those who achieved ≥50% reduction in depressive symptoms) were evaluated again at 1-, 3-, and 6-month follow-up visits. < .001), with no significant differences in task performance associated with response to either treatment. Among responders, we observed no significant group differences at 1-, 3-, and 6-month follow-up. Analyses of subjective memory questionnaires were mixed. SMCQ scores improved for both groups with ketamine recipients reporting greater functional gains; ketamine-treated patients reported improvements in GSE-My scores while ECT-treated patients reported a decline in GSE-My scores. Within-group analyses in the ketamine group found improvements in executive functioning and cognitive flexibility. This survived adjustments for changes in depression, suggesting partial independence of cognitive and mood effects. Patients treated with ketamine demonstrated superior cognitive functioning compared with those treated with ECT following a 3-week treatment course, with no differences between treatments observed among responders in follow-up. Findings support the short-term superiority of ketamine on cognitive functioning and the long-term cognitive safety of both treatments for TRD. ClinicalTrials.gov identifier: NCT03113968.