Administration of Sub-anesthetic Dose of Ketamine and Electroconvulsive Treatment on Alternate Week Days in Patients with Treatment Resistant Depression: A Double Blind Placebo Controlled Trial
Murat Altinay, Harish Karne, Amit Anand
Psychopharmacology Bulletin August 12, 2025 DOI: 10.64719/pb.4588 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Patients with treatment-resistant depression (failed at least two antidepressants in the current episode); 15 recruited, 12 analyzed |
| Interventions | Ketamine ECT midazolam |
| Measures | 17-item Hamilton Depression Rating Scale (HAM-D), Young Mania Rating Scale, cognitive tests |
| Topics | Depression Esketamine Ketamine |
| Key findings | Ketamine and placebo groups did not differ on change in HAM-D, Young Mania Rating scores, or cognitive tests. Early remission (HAM-D < 8) occurred in 3 of 7 ketamine patients (42%) versus 0 of 5 placebo patients (0%), a trend-level difference (chi-square p = 0.0910). The authors suggest ketamine plus ECT may lead to faster symptom relief but note the small sample limits conclusions. |
Abstract
Introduction and Background Patients with depression who fail to respond to at least two antidepressants in their current episode are considered to have Treatment Resistant Depression (TRD). ECT is an effective treatment of TRD but cognitive side effects limit its use. Ketamine elicits a rapid antidepressant response in sub-anesthetic repeated doses. ECT and ketamine may be modulating the glutamate system, therefore when administered in an interleaved fashion, they could have a synergistic effect.
Methods: 15 TRD patients were recruited and 12 were included in the analysis. Patients were randomly assigned to an ECT + iv. ketamine or ECT + iv. placebo (midazolam). At baseline and before each infusion, depression severity scales were administered. At baseline, halfway through and at the end of the study, cognitive tests were administered.
Results: There was no difference between the ketamine and placebo arms, per change in 17-item Hamilton Depression Scores (HAM-D), Young Mania Rating Scores or cognitive tests. Per HAMD scores, 3 ECT +ketamine subjects (42%) showed early remission (HAMD < 8) and maintained euthymia for 3 additional visits. None of the ECT +midazolam subjects (0%) achieved early remission. This difference showed a trend level significance (Chi square P-Value = 0.0910).
Conclusion: The results of the study were limited due to the small sample size. However, a trend level difference in rates of early remission was seen, suggesting that ketamine + ECT may lead to a faster symptom relief. A larger sample size is needed for statistical confirmation.