Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial (KetECT)
Joakim Ekstrand, Christian Fattah, Marcus Persson, Tony Cheng, P. Nordanskog, J. Åkeson, A. Tingström, Mats B Lindström, A. Nordenskjöld, Pouya Movahed Rad
International Journal of Neuropsychopharmacology December 4, 2021 DOI: 10.1093/ijnp/pyab088 via Semantic Scholar
Summary
For severely depressed inpatients aged 18–85, electroconvulsive therapy (ECT) led to remission in 63% of patients, while ketamine infusions led to remission in 46%, a statistically significant difference. Both treatments required a median of six sessions to achieve remission. ECT caused more serious and long-lasting side effects, including persisting amnesia, whereas ketamine caused more treatment-emergent adverse events leading to dropouts. Among those who remitted, about two-thirds in each group relapsed within 12 months, with no significant difference between treatments. Ketamine, though less effective than ECT, appears to be a safe and useful option for treating unipolar depression.
Study at a glance
| Characteristics | Randomized controlled trial Open-label Peer reviewed |
|---|---|
| Sample size | 186 |
| Population | Hospitalized patients with unipolar depression aged 18-85 |
| Keywords | Medicine |
| Citations | 112 |
| Key finding | ECT produced a higher remission rate (63%) than ketamine (46%) in severely depressed inpatients, but ketamine had fewer serious long-term adverse effects. |
Abstract
Abstract Background Ketamine has emerged as a fast-acting and powerful antidepressant, but no head to head trial has been performed, Here, ketamine is compared with electroconvulsive therapy (ECT), the most effective therapy for depression. Methods Hospitalized patients with unipolar depression were randomized (1:1) to thrice-weekly racemic ketamine (0.5 mg/kg) infusions or ECT in a parallel, open-label, non-inferiority study. The primary outcome was remission (Montgomery Åsberg Depression Rating Scale score ≤10). Secondary outcomes included adverse events (AEs), time to remission, and relapse. Treatment sessions (maximum of 12) were administered until remission or maximal effect was achieved. Remitters were followed for 12 months after the final treatment session. Results In total 186 inpatients were included and received treatment. Among patients receiving ECT, 63% remitted compared with 46% receiving ketamine infusions (P = .026; difference 95% CI 2%, 30%). Both ketamine and ECT required a median of 6 treatment sessions to induce remission. Distinct AEs were associated with each treatment. Serious and long-lasting AEs, including cases of persisting amnesia, were more common with ECT, while treatment-emergent AEs led to more dropouts in the ketamine group. Among remitters, 70% and 63%, with 57 and 61 median days in remission, relapsed within 12 months in the ketamine and ECT groups, respectively (P = .52). Conclusion Remission and cumulative symptom reduction following multiple racemic ketamine infusions in severely ill patients (age 18–85 years) in an authentic clinical setting suggest that ketamine, despite being inferior to ECT, can be a safe and valuable tool in treating unipolar depression.