Supplementary Material for: A Randomized Controlled Trial on the Efficacy of Ketamine vs. Electroconvulsive Therapy in Severe Depression with Suicidal Ideation

Background: Severe depressive episodes with suicidal ideation present major therapeutic challenges and often require interventions beyond standard antidepressant therapy. Electroconvulsive therapy (ECT) remains a cornerstone treatment for refractory depression, while ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has emerged as a rapid-acting antidepressant with potential benefits in reducing suicidal ideation. This study compares the efficacy, onset of action, and tolerability of intravenous ketamine and ECT as adjunctive treatments in severe major depressive disorder with active suicidal ideation.

Methods: A randomised controlled trial was conducted at a tertiary care psychiatry department in India, enrolling 64 patients aged 18–60 years with severe depression (HAM-D ≥ 19, SSI ≥ 4). Participants were randomly assigned to receive either intravenous ketamine (n = 31) or ECT (n = 33), alongside ongoing oral antidepressants. Both groups underwent six treatment sessions over two weeks. Outcomes were assessed at baseline, post-treatment, and four weeks after completion. Primary endpoints included changes in depression severity (HAM-D) and suicidal ideation (SSI), while secondary outcomes included response and remission rates, as well as safety and tolerability profiles.

Results: Both ECT and ketamine significantly reduced depressive symptoms and suicidal ideation (p < 0.001). HAM-D scores declined from 27 to 1 in the ECT group and from 26 to 2 in the ketamine group by the 4-week follow-up. SSI scores showed parallel improvement, from 12.1 to 1.2 with ECT and 12.6 to 2.0 with ketamine. Ketamine demonstrated a faster onset of clinical improvement, while ECT showed slightly greater durability of response. Side effects were mild in both groups, though ECT was associated with transient cognitive impairment, whereas ketamine produced minor dissociative and urinary symptoms.
Conclusion: Ketamine offers a faster reduction in suicidal ideation than ECT, making it a promising acute intervention. Both are effective, safe adjunctive therapies, with treatment choice guided by patient profile and tolerability.