3 Clinical psychopharmacology3.3 Pharmacodynamics
3.3.7 Putative neurochemical changes associated with ECT
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Written by Resident Doctor Committee · Published
The seizure as the starting point
An adequate induced seizure is central to how ECT works, and benefit builds across a course of usually 6 to 12 treatments.
Seizures acutely release monoamines, glutamate, GABA and neuropeptides, which may start adaptation without explaining later benefit.
ECT acutely releases prolactin, adrenocorticotropic hormone, cortisol, vasopressin and oxytocin.
Receptor changes
Receptor | Repeated ECT | Long-term antidepressants |
|---|---|---|
Postsynaptic beta-adrenergic | Downregulated | Downregulated |
5-HT2A | Upregulated | Downregulated |
ECT and antidepressants may reach a similar outcome through different initial pathways.
Changes after a course
Measure | Direction | Note |
|---|---|---|
Hippocampal brain-derived neurotrophic factor (BDNF) | Rises | The most consistent neurochemical effect; signals through TrkB to support plasticity |
Hippocampal volume | Rises | Amygdala volume often rises too; does not consistently track improvement |
Cortical GABA | Rises | |
Seizure threshold | Rises | Basis of the anticonvulsant hypothesis |
N-acetylaspartate | Falls, reversibly | Spectroscopic marker of neuronal integrity |
N-acetylaspartate is the measure that falls, while the others rise.
The anticonvulsant hypothesis links benefit to stronger inhibition involving GABA and adenosine, but threshold rise and response are inconsistently linked.
Limits of the evidence
Much mechanistic evidence comes from animals, and peripheral biomarkers and imaging are indirect.
Changes may cause, follow or merely accompany improvement, so no single model explains the benefit.