Mar 22 2012

How Electroconvulsive Therapy Works

Electroconvulsive therapy, or ECT, has been used for about 70 years and yet remains a controversial treatment. There is no real controversial over whether or not ECT works for depression – it is highly effective. The controversy is over the invasiveness and side effects. The controversy is also partly driven by the fact that we’re not sure how it works, so a new study shedding light on this question may change the debate.

ECT is the application of an electrical current to the temples in order to induce a seizure. It is used in severely depressed patients who are not responding to medication and therapy. The major side effect is memory loss, which can be significant. Over the years researchers have discovered how to make the procedure less and less invasive and traumatic. Forget that scene from One Flew Over the Cuckoos Nest, that’s old school. Patient are now given medication so that they are sedated and paralyzed so that they don’t convulse. Further, researchers learned that doing ECT to one hemisphere is just as effective as two, with fewer side effects. Researchers continue to tweak the dose of ECT to find the optimal benefit with least side effects, but there is no way with current ECT to eliminate the side effects, specifically the memory loss.

It has not been know exactly how ECT works. It is known that ECT reduces brain activity and raises seizure threshold (makes it less likely to have a seizure).  This implies that overall neuronal activity is reduced, so perhaps ECT is inhibiting overactivity in a part of the brain that is driving the depression. That hypothesis is supported by a recent study that uses fMRI scanning to look at brain activity in nine patients with major depression before and after ECT. They found:

A comparison of pre- and posttreatment functional connectivity data in a group of nine patients revealed a significant cluster of voxels in and around the left dorsolateral prefrontal cortical region (Brodmann areas 44, 45, and 46), where the average global functional connectivity was considerably decreased after ECT treatment (P < 0.05, family-wise error-corrected). This decrease in functional connectivity was accompanied by a significant improvement (P < 0.001) in depressive symptoms

Once way to interpret this result is that some patients with major depression have overactive connectivity between that part of the brain that generates the emotion of depression and the part of the brain involved in cognition and concentration. In these patients, therefore, their depressed mood has a significant effect on their thoughts and ability to concentrate. ECT appears to reduce this hyperconnectivity, which should significantly reduce the symptoms of depression.

This is all consistent with prior research on depression, and makes good sense. Still, it’s a small study that needs to be replicated and the whole question further explored. Assuming that the finding holds up, it does suggest the possibility of treating depression with less invasive interventions with fewer side effects. It may provide new targets for drug therapy, as well as a method for monitoring the effects of medication. It may also lead to more targeted non-pharmacological therapy. Perhaps, for example, we can use transcranial magnetic stimulation (TMS ) to specifically turn down just that one area of hyperconnectivity. This would be a good test of the hypothesis, and confirm the above findings if it works. It could also be an effective treatment for depression with much fewer side effects than ECT.

Right now ECT is a fairly crude treatment, inducing a seizure and affecting the whole brain. With TMS we could potentially target just one area of the brain – like using a scalpel instead of a sledge hammer. Other technologies that alter the hardwiring of the brain may also come into play, once we know what circuitry is causing depression in the first place. For example, implantable computer chips that alter brain activity.

This study shows the potential of new technology to improve our understanding of brain function, in both the healthy and disordered state, and create the opportunity to craft more targeted therapy. I hope this is another indication that we are shifting from our current therapeutic paradigm of treating the whole brain (whether with drugs or ECT) to therapies that can target specific brain circuits that are misbehaving.

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