Electroconvulsive therapy (ECT) and ketamine are among the most effective and rapidly acting treatments available for patients with severe and treatment-resistant depression. Over the past several years, multiple randomized trials and meta-analyses have compared these two interventions—yet conclusions have often been conflicting, leaving clinicians uncertain about how best to interpret the evidence.
A newly published systematic review and meta-analysis provides important clarity by addressing a critical and frequently overlooked factor: time.
Why This Study Matters
Most prior meta-analyses comparing ECT and ketamine relied on single “endpoint” assessments, despite substantial variation in treatment duration and assessment timing across trials. This approach risks comparing outcomes measured at fundamentally different points in the treatment course—effectively comparing apples to oranges.
This new analysis takes a different, more clinically meaningful approach by modeling symptom change over time, enabling a direct comparison of improvement rates rather than isolated endpoints. This methodological advance helps explain why earlier meta-analyses reached divergent conclusions and offers more actionable guidance for real-world clinical decision-making.
Study Overview
By including all available assessment time points and adjusting for baseline differences, the authors were able to model how depressive symptoms evolved throughout treatment rather than relying on a single snapshot.
Key Findings
After adjusting for baseline depression severity, ECT was associated with a faster daily rate of improvement, corresponding to an advantage of approximately 0.02 standardized mean difference (SMD) per day.
Over a typical four-week treatment course, this accumulated to a moderate efficacy advantage for ECT (SMD ≈ 0.59)—a difference that falls within the range considered clinically meaningful.
Patients randomized to ketamine entered treatment with lower baseline depression severity than those receiving ECT. This imbalance—previously underappreciated—likely contributed to inconsistent findings across earlier meta-analyses and underscores the importance of adjusting for baseline severity when comparing antidepressant treatments.
The findings do not contradict the well-established observation that ketamine produces a rapid, early antidepressant effect, often within hours of the first administration. Instead, the data suggest that while ketamine acts quickly, ECT catches up and surpasses ketamine over time, leading to greater cumulative improvement by the end of a multi-week course.
Clinical Implications
For clinicians treating patients with severe or treatment-resistant depression, this study reinforces several key principles:
Rather than positioning ECT and ketamine as competing therapies, these findings support a complementary, stage-based approach—one that aligns treatment selection with illness severity, urgency, and long-term treatment goals.
Looking Ahead
This analysis highlights the need for future comparative trials to:
As interventional psychiatry continues to evolve, methodologically rigorous studies like this one help move the field beyond oversimplified comparisons toward precision-informed, time-aware treatment strategies.
Reference
Nikolin S, Massaneda-Tuneu C, Brettell L, Loo C. Time matters for metas: a systematic review and meta-analysis of ECT vs ketamine for depression incorporating time. Translational Psychiatry. 2026.
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Disclaimer
This article was created with the assistance of artificial intelligence (AI) to support clarity and readability. All medical content has been reviewed and approved by Joao L. de Quevedo, MD, PhD, Director of the UTHealth Houston Center for Interventional Psychiatry. This content is for educational purposes only and does not substitute for professional medical advice.