TL;DR
- •ECT (electroconvulsive therapy) has been the gold standard for severe treatment-resistant depression for decades, with response rates of 60-80% in severe cases. Ketamine is a newer NMDA-receptor antagonist with rapid onset and comparable efficacy in non-severe TRD.
- •Anand 2023 (NEJM) randomized 403 patients with non-psychotic treatment-resistant depression to ECT or ketamine — ketamine was non-inferior to ECT in response rates with fewer cognitive side effects.
- •ECT requires general anesthesia and induces a controlled brief seizure. Memory effects (anterograde amnesia during treatment, occasional retrograde amnesia) are the main concern, partly mitigated by right-unilateral electrode placement.
- •Ketamine is given without anesthesia. Side effects are dissociation during sessions and rare bladder issues with chronic high-dose use — no memory effects of the ECT kind.
- •ECT is preferred over ketamine for severe depression with psychotic features, catatonia, or pregnancy-related severe depression where pharmacological options are constrained.
- •Ketamine is increasingly preferred for non-severe TRD given the comparable efficacy and lower side-effect burden — sublingual at-home administration has further widened the access gap.
- •Both can be sequenced — patients who fail one frequently respond to the other given the different mechanisms.
Side by side
ECT
Electroconvulsive Therapy
Neurostimulation under general anesthesia
What it treats
Severe TRD, Severe depression with psychotic features, Catatonia, Severe mania, Bipolar depression refractory
Mechanism
Brief electrical current induces a controlled generalized seizure under general anesthesia. Hypothesized mechanisms include neurotrophic factor release, synaptic plasticity, and HPA axis recalibration. Mechanism still incompletely understood despite ~80 years of clinical use.
Strengths
- •Highest response rate of any depression treatment in severe cases (~60-80%)
- •Effective for psychotic depression where ketamine and most antidepressants aren't
- •First-line for catatonia
- •Effective in pregnancy when medication options are constrained
- •Decades of safety data
Limitations
- •Memory effects — anterograde amnesia common; retrograde amnesia possible
- •General anesthesia required for each session
- •Can't drive on treatment days
- •Stigma + complex scheduling
- •Maintenance ECT typically needed to prevent relapse
Ketamine
Racemic ketamine (NMDA antagonist)
NMDA-receptor antagonist (off-label for depression)
What it treats
Off-label: treatment-resistant depression, anxiety, PTSD, FDA-approved: anesthesia
Mechanism
NMDA-receptor antagonism producing acute glutamate surge and BDNF-mediated synaptic plasticity. Rapid antidepressant effect emerges within hours, often before the dissociative experience resolves.
Strengths
- •No anesthesia required, no seizure
- •No memory effects of the ECT type
- •Rapid onset (hours)
- •At-home administration option (sublingual)
- •Lower per-course cost than ECT
Limitations
- •Off-label use for depression specifically (esketamine/Spravato is FDA-approved variant)
- •Not first-line for psychotic depression or catatonia
- •Dissociation during sessions can be uncomfortable for some patients
- •Less efficacy data in the most severe (psychotic, catatonic) presentations
Which one for your situation?
If:
Severe TRD with psychotic features
Verdict:
ECT — first-line for psychotic depression; ketamine isn't typically effective
If:
Catatonia (mutism, immobility, posturing)
Verdict:
ECT — first-line treatment for catatonia
If:
Non-psychotic moderate-to-severe TRD
Verdict:
Per Anand 2023 NEJM, ketamine is non-inferior to ECT with fewer cognitive side effects — reasonable to try first
If:
Pregnant patient with severe depression
Verdict:
ECT is the most-studied option in pregnancy when medication is constrained; ketamine's pregnancy data is more limited
If:
Memory effects are a hard constraint (cognitively demanding profession, autobiographical importance)
Verdict:
Ketamine — no comparable memory effect profile
If:
Failed ECT — what's next?
Verdict:
Ketamine is the typical next-tier option; different mechanism, often responds where ECT didn't
Where ketamine fits
Tovani provides sublingual ketamine via telehealth in Florida and New Jersey — a non-ECT option for treatment-resistant depression without the anesthesia, memory effects, or in-clinic burden of ECT. The Anand 2023 NEJM trial established ketamine's non-inferiority in non-psychotic TRD. ECT remains the right choice for severe psychotic or catatonic presentations.
ECT: response measured at 1-2 weeks of 2-3x weekly sessions. Ketamine: response within hours of first session. Both produce lasting effects with maintenance dosing.
5-minute screening · Reviewed by a board-certified physician · FL & NJ
Frequently asked
Is ECT still used?
Yes — ECT remains a widely-practiced and effective treatment for severe depression, particularly in academic medical centers and for the most severe presentations (psychotic depression, catatonia, severe mania). It has decades of safety data and the highest response rates of any depression treatment in severe cases. Stigma has decreased somewhat but persists; technique has refined substantially since the early decades of use.
Will ECT erase my memories permanently?
Generally no, but memory effects are the most well-known ECT side effect. Anterograde amnesia (difficulty forming new memories during treatment) is common but typically resolves weeks after treatment ends. Retrograde amnesia (losing memories of events before treatment) occurs in a subset of patients and can be more persistent. Right-unilateral electrode placement and ultrabrief pulse settings reduce memory effects while maintaining efficacy.
How did Anand 2023 change the conversation?
The Anand 2023 NEJM trial randomized 403 patients with non-psychotic treatment-resistant depression to ketamine or ECT and found ketamine non-inferior in response rates. Ketamine patients had fewer cognitive side effects. This evidence supports trying ketamine before ECT in non-psychotic TRD when both options are available. ECT remains preferred for psychotic, catatonic, or severely suicidal presentations.
Can I do ketamine if ECT didn't work?
Yes — and often. The mechanisms are different (controlled seizure + neurotrophic effects vs NMDA antagonism), so patients who don't respond to one frequently do respond to the other. After ECT failure, ketamine is the most common next-tier escalation. The reverse sequence (failed ketamine → ECT) is also clinically standard.
Which is safer overall?
Both have established safety profiles in their protocols. ECT involves general anesthesia (a small but real risk per session) and memory effects. Ketamine involves dissociation during sessions and rare bladder issues with chronic high-dose use. For most patients, ketamine has a lower side-effect burden; for severely ill patients where rapid stabilization matters more than side effects, ECT's higher response rate may be worth the trade-off.
References
- Anand A et al. 2023, New England Journal of Medicine. RCT of ketamine vs ECT in non-psychotic treatment-resistant depression — 403 patients, ketamine non-inferior to ECT in response rates with fewer cognitive side effects. PMID 37224232
- Murrough JW et al. 2013, American Journal of Psychiatry. Ketamine RCT in treatment-resistant depression — 64% response vs 28% placebo, establishing the rapid-onset antidepressant mechanism. PMID 23982301
- Sanacora G et al. 2017, JAMA Psychiatry. APA consensus on ketamine use in mood disorders, addressing ketamine's positioning relative to ECT in TRD escalation. PMID 28249076
- Mathiassen AB et al. 2026, British Journal of Psychiatry. Systematic review and meta-analysis of autobiographical memory effects after ECT. PMID 40357797