How electroconvulsive therapy works in the treatment of depression: is it the seizure, the electricity, or both?

Abstract We have known for nearly a century that triggering seizures can treat serious mental illness, but what we do not know is why. Electroconvulsive Therapy (ECT) works faster and better than conventional pharmacological interventions; however, those benefits come with a burden of side effects, most notably memory loss. Disentangling the mechanisms by which ECT exerts rapid therapeutic benefit from the mechanisms driving adverse effects could enable the development of the next generation of seizure therapies that lack the downside of ECT. The latest research suggests that this goal may be attainable because modifications of ECT technique have already yielded improvements in cognitive outcomes without sacrificing efficacy. These modifications involve changes in how the electricity is administered (both where in the brain, and how much), which in turn impacts the characteristics of the resulting seizure. What we do not completely understand is whether it is the changes in the applied electricity, or in the resulting seizure, or both, that are responsible for improved safety. Answering this question may be key to developing the next generation of seizure therapies that lack these adverse side effects, and ushering in novel interventions that are better, faster, and safer than ECT.