Why Compare Ketamine and ECT?
For people with treatment-resistant depression (TRD), finding relief often requires advanced therapies. Electroconvulsive therapy (ECT) has long been one of the most effective options, but it comes with concerns about memory problems and other cognitive side effects. Intravenous ketamine, on the other hand, has gained attention for its rapid antidepressant effects and potential to improve thinking and memory.
Researchers in the ELEKT-D trial set out to compare the cognitive effects of ketamine vs ECT head-to-head in a large group of patients. The goal was to see not only which treatment reduced depressive symptoms but also how each affected brain functions like memory, attention, and flexibility.
How the Study Was Designed
The ELEKT-D trial, conducted between 2017 and 2022, enrolled 365 patients with treatment-resistant depression across multiple sites. Participants were randomly assigned to receive either six intravenous ketamine infusions or nine sessions of ECT.
Cognitive function was measured before and after treatment using validated tasks that assess memory, executive functioning, and flexibility in problem-solving. In addition, participants filled out self-reported questionnaires, including the Squire Memory Complaint Questionnaire (SMCQ) and the Global Self-Evaluation of Memory (GSE-My). Responders—those who achieved at least a 50 percent reduction in depressive symptoms—were followed for up to six months.
Findings on the Cognitive Effects of Ketamine vs ECT
At the end of treatment, patients who received ECT performed significantly worse than those who received ketamine on all objective cognitive tasks. This suggests that ketamine may protect or even enhance certain aspects of cognition in the short term.
Self-reports told a more nuanced story. Both groups reported improvements in everyday memory complaints, but ketamine recipients described greater functional gains. Interestingly, patients who received ketamine felt their memory improved, while those who had ECT felt it declined.
Importantly, when looking at responders over time, the differences evened out. At one-, three-, and six-month follow-ups, there were no significant differences between ketamine and ECT in cognitive performance. This finding reassures clinicians and patients that, despite short-term setbacks with ECT, both treatments appear cognitively safe over the long run.
The Independence of Mood and Cognition
One striking aspect of the study was that improvements in thinking skills among ketamine patients held up even after adjusting for changes in depression severity. This suggests that ketamine may have direct pro-cognitive effects beyond simply improving mood. For example, executive functioning and cognitive flexibility improved in the ketamine group, potentially helping patients regain problem-solving abilities and mental clarity more quickly.
What This Means for Patients and Clinicians
The cognitive effects of ketamine vs ECT are now clearer: ketamine shows advantages in the short term, particularly in how patients perceive their own memory and in objective test results. ECT, while highly effective for severe depression, carries a greater risk of temporary cognitive side effects, though these appear to fade with time.
For clinicians, this study supports offering ketamine as a promising option when concerns about cognition are front and center. For patients, it reinforces the idea that both therapies remain viable, safe, and effective paths toward recovery—each with unique benefits and considerations.
Looking Ahead
This trial highlights the need for personalized approaches in interventional psychiatry. Some patients may prioritize rapid relief with fewer cognitive effects, making ketamine attractive. Others may respond more reliably to ECT despite its temporary drawbacks. Future research will likely focus on combining or sequencing these treatments, tailoring care to individual needs, and exploring the brain mechanisms that explain ketamine’s cognitive edge.
Learn more at https://interventionalpsychiatry.org/
References
- Kumpf KT, Wilkinson ST, Hu B, et al. Comparing the Cognitive Effects of Repeated Intravenous Ketamine and Electroconvulsive Therapy in Patients With Treatment-Resistant Depression: A Secondary Analysis of the ELEKT-D Trial. J Clin Psychiatry. 2025. PMID: https://pubmed.ncbi.nlm.nih.gov/40900112/
- Andrade C. Ketamine for Depression: Efficacy, Safety, and the Cognitive Dimension. J Clin Psychiatry. 2023. PMID:https://pubmed.ncbi.nlm.nih.gov/37539341/