PsyDactic

ECT: A method to the madness

December 28, 2021 T. Ryan O'Leary Episode 3
PsyDactic
ECT: A method to the madness
Show Notes Transcript

The mechanism of action of electroconvulsive therapy remains elusive, so I am going to describe how ECT induces seizures, discuss the evidence that ECT is not just an elaborate placebo (or in other words, inducing the seizure is what results in the therapeutic benefit), and then briefly discuss some of the many proposed mechanisms by which it might work.

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Welcome to PsyDactic - Residency Edition - Your podcast resource to survive and thrive in your psych residency.


I am Dr. O’Leary, and as of this recording I am a 2nd Year Resident  in the National Capital Consortium Psychiatry Residency Program.  However, make no mistake, I do not speak for this program, nor do I speak for the Department of Defense or the Federal Government or anyone else for that matter.  What I say is my opinion, and I reserve the right to be wrong, so trust me at your own risk.  It’s a risk some are willing to take.


In the last episode I gave a brief history of ECT, but in this episode I want to zoom in. I want to explore the mechanism of action of ECT, electroconvulsive therapy.  To say the mechanism of ECT is the induction of convulsive seizures is like saying the mechanism of action of hydraulic erosion is water touching rocks.  It is more descriptive than explanatory.  The mechanism of action remains elusive, so what I am going to do instead is to describe how ECT induces seizures, discuss the evidence that ECT is not just an elaborate placebo (or in other words, inducing the seizure is what results in the therapeutic benefit), and then briefly discuss some of the many proposed mechanisms by which it might work.


When I grab a prodigal screwdriver from my son’s hand while he is attempting to insert it clumsily into the wall outlet, what I am preventing him from doing is flooding his body with an excess of electrons.  Likely, a flood of electrons passing through his spaghetti sauce stained fingers would result in diffuse muscle contractions, the disruption of electricity through his heart, and parts of his body or clothing potentially could catch fire from the heat generated from the resistance to electrical flow.  That’s the long way of describing his impending death.  But it would also likely be a peaceful death, at least from his point of view, as he would likely lose consciousness immediately.  So why doesn’t ECT kill it’s patients?


The electricity delivered to patients is tightly controlled in amount and location.  When Lucio Bini first experimented on delivering electricity to dogs, he placed electrodes in the mouth and the anus, resulting in a large amount of the current running directly through the poor beast’s heart, resulting in death in a large portion of his formerly tail-wagging victims.  This is because electrons, like rivers, take the path of least resistance.  By shocking dogs in their bilateral temples, however, resistance to flow of electricity to the heart was high enough to result in a seizure without producing death.


When the originators of ECT first shocked heads, they did so by controlling the voltage and duration of the shock.  Voltage is defined as the current multiplied by the resistance, which can be conceptualized as the total amount of electricity available to be delivered or the force driving electricity forward.  You can increase voltage by increasing the current or by increasing the resistance.   Most devices now adjust for a constant current, which might be seen as the total amount of electricity actually delivered.  This gives more consistent results than just hooking straight up to a 120V outlet.


When electricity is delivered to the body, it encounters varying resistance, from the connection points, the hair, skin, fat, connective tissues, bones, etc.  This means that only a small amount of the current given to a person actually makes it to the brain.  If we could shock the brain directly, or drill a hole in the skull, we could turn the current way down.  But to penetrate that thick skull and make you seize we need ample current, and the amount needed can vary greatly between people.

 

It is important to note that seizure is the important thing here.  The elaborate nature of an ECT session at first made it seem possible that the benefit people derived was due entirely to a placebo response.  Having experienced such heroic efforts at a cure, the patient was likely to feel better, or at report feeling much better.  It is unclear how a catatonic patient could respond to a placebo, but not so hard in depressed patients, so it was necessary to test this idea.  There have been experiments where some patients are anesthetized and given ECT, some are anesthetized and not given ECT.  Those without ECT were also without benefit.   There was also a priori evidence that ECT would work because chemically induced seizures worked as well, but over-all the tolerability and safety of electrically induced seizures is much better.  Another line of evidence that ECT is in fact directly responsible for improvements in affective and catatonic symptoms is that other brain stimulation therapies as of yet can’t compete with the efficacy of ECT, though they do have a lower side effect profile.


Here I’ll quote: MAX FINK, MD (Induced Seizures as Psychiatric Therapy

Ladislas Meduna’s Contributions in Modern Neuroscience


All alternative methods of brain stimulation,

whether by medications, electricity, or magnetism that

fail to induce bilateral grand mal seizures are less effective

than seizure inducing methods.


So the point of this is that ECT works by generating a generalizing seizure and not by some other ghostly effects of actual or animal magnetism.  What we don’t know is how inducing a seizure actually helps.  If you recall from the ECT History episode, Ladislas Meduna thought that seizures somehow increase glial cells in the brain which he postulated was protective against psychosis.  This is called “antagonism” when one disease basically cures or prevents another.


There were a number of so-called “psychological” mechanisms proposed that make very little sense to a guy like me.  Psychoanalysis was still gaining popularity with ECT was invented, so they were remiss not to weigh in.  Whether ECT pushes patients to some fearful, or punished, or regressed, child-like state that somehow changes the course of the present illness sounds more like a scene from the HBO series The Doom Patrol than anything credible.  ECT also probably doesn’t make us “forget” why we are sad.  There is some transient periprocedural amnesia, but patients' access to their long term memories return over time.


While we can’t see measurable changes in the ego, after a seizure there are some measurable changes in the brain, including decreased metabolic rate, decreased blood flow, increase in slow waves, and a relative increase in inhibitory neurotransmission.  Seizure thresholds tend to increase during a course of treatment, requiring more and more electricity to induce the generalized convulsions. At the same time, the duration of the seizures decreases.  So we have an increase in threshold and a decrease in seizure duration throughout the course of treatment.  It is unclear how or if these changes are related to the treatment effects.


The sustained production of slow waves on EEG after ECT is associated with improvement, and these slow waves are a result of the inhibition of or hyperpolarization of pyramidal cells.  Researchers have also noticed reduced blood flow to and metabolic activity of the anterior frontal lobes that can last for months after ECT.  This finding has been associated with better outcomes.  So in general, maybe there are specific areas of inhibition of neurotransmission after seizure that results in clinical improvement.  There is also evidence of increased GABA activity in brains after ECT and decreased GABA activity in previously depressed brains.


Others say maybe the whole problem for mood and psychotic disorders is that people aren’t sleeping well, and ECT fixes that somehow, or at least helps alleviate it by inducing those slow waves that are similar to sleep waves, but there is little other evidence for this.


In a similar way that Meduna thought that seizure increased glial cells in the brain, some have proposed that ECT somehow induces neural regeneration or neurogenesis, especially in the hippocampus and diencephalon (which is all those “thalamusy” parts of the brain.)  This is thought to be somehow mediated through our friendly neighborhood signal molecule and neural rejuvenator, brain derived neurotropic factor (BDNF).


Others have proposed that ECT works through hormone release.  This is call the neuroendocrine hypothesis and is posits that brain associated endocrine organs such as the hypothalamus or pituitary gland release hormones, including prolactin, thyroid stimulating hormone, or adrenocorticotropic hormone, but there is little evidence that this is the case.


Maybe you’ve heard of the monoamine hypothesis, which proposes that deficiencies in neurotransmission of dopamine, serotonin, or norepinephrine drive depressive symptoms among other things.  Some propose that ECT causes a predictable modulation of the monoamines in the brain.  I will vastly over simplify a lot of research here by saying that the evidence supporting this is inconclusive at best, and you should consult an ECT expert if you want the low-down.  But I will say that, ECT seems to operate differently because it is still very effective in patients who have failed to respond to mono-amine targeting pharmacotherapies, suggesting, maybe, a different mechanism.


One might ask, since ECT is so effective already, with remission rates of depression as high as 80-90%, does knowing the mechanism of action really even matter?


Well, if we know what ECT was doing to remit depression, we might be able to develop more targeted approaches that don’t require convulsive seizures.  Because ECT affects the whole brain, it may be treating depression merely by accident, in the same way a baby peeing into the air might accidentally get some of it’s urine in your mouth.  If it pees all over everything then, well, I think you get the picture.


TMS (transcranial magnetic stimulation of the brain) is a more target, non-siezure inducing method, that has some efficacy in depression and is hoping to discover exactly where to target magnetic fields which deliver far less electromagnetic energy than ECT.  TMS developers  hope to achieve a similar effect as ECT.  They are not there yet.


In the next episode, I will explore the indications for ECT, when you may consider referring a patient to ECT, and if I’m lucky, I’ll have room to explore how to explain ECT to your patient.


Thank you for your time, and this has been an episode of PsyDactic - Residency Edition. 1–5

Bibliography

1. Mankad MV, Beyer JL, Weiner RD, Krystal A. Clinical Manual of Electroconvulsive Therapy. 1st ed. American Psychiatric Publishing, Inc.; 2010:239.

2. Fink M. Induced seizures as psychiatric therapy. J ECT. 2004;20(3):133-136. doi:10.1097/00124509-200409000-00001

3. Grover E, Mattoo S, Gupta N. Theories on Mechanism of Action of  Electroconvulsive Therapy. The German Journal of Psychiatry. Published online January 10, 2005.

4. Rosenquist PB, McCall WV, Youssef N. Charting the course of electroconvulsive therapy: where have we been and where are we headed? Psychiatr Ann. 2016;46(11):647-651. doi:10.3928/00485713-20160927-01

5. Heijnen WT, Birkenhäger TK, Wierdsma AI, van den Broek WW. Antidepressant pharmacotherapy failure and response to subsequent electroconvulsive therapy: a meta-analysis. J Clin Psychopharmacol. 2010;30(5):616-619. doi:10.1097/JCP.0b013e3181ee0f5f