Electroconvulsive Therapy: Why is it Effective? A Challenge to the Modes of Action

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Biology 202
2002 Third Paper
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Electroconvulsive Therapy: Why is it Effective? A Challenge to the Modes of Action

Cass Barnes

Reported for the first time in the 18th century, was the use of convulsive therapy. Psychiatrists observed that after spontaneous epileptic seizure the psychiatric conditions of patients improved. Previously, in the sixteenth-century, Paracelsus, a Swiss physician and alchemist gave camphor by mouth to produce convulsions and to cure lunacy. Originally, the induced convulsions treated severe catatonic stupors and schizophrenia. Today we know the convulsions are secondary to grand mal seizures in the brain, and that the seizure is the primary therapeutic agent of electroconvuslive therapy (ECT). Metrazol and Cardiazol later replaced Camphor because of its rapid onset. The extremely unpleasant sensations led investigators to seek alternative methods and electroconvulsive therapy was born. Electrical stimulation first tested epileptic seizures on dogs and pigs, and its first treatment helped a delusional, hallucinating homeless man diagnosed with schizophrenia in 1938. After chronic administration of ECT, the patient fully recovered.

The introduction of ECT to the United States created a burst of therapeutic optimism in psychiatry. Psychiatrists used ECT experimentally on patients with major mental disorders. This led to its current use for Major Depression. A negative stigma has remained since movies like One Flew Over the Cuckoo's Nest stress the abuse of ECT: "The Shock Shop, Mr. McMurphy . . . might be said to do the work of the sleeping pill, the electric chair and the torture rack. It's a clever little procedure, simple, quick, nearly painless it happens so fast, but no one ever wants another one. Ever".

The idea that all the Doctor has to do is "push the button" and hope for the best, while prolonging the electric shock for hours at a time, to increase the effectiveness, instills the fear that ECT will be a horrific traumatic experience with brain damage and severe side effects. It is possible that this may have existed in the times of asylums as a form of punishment, but today, doctors are more careful and familiar with the equipment to produce positive effects.

However, there still remains controversy. There remains controversy because some experience more negative effects than they do positive effects. Negative results include side effects, relapse, and possible death. On the other hand, the positive result is an immediate anti-depressant effect despite the possible side effects and relapse. Some argue however, "There is no controversy about the indications for ECT and its efficacy in alleviating severe mood disorders, not about the safety of the procedure when properly done" (2). There are those who argue that ECT is brain-damaging or brain-disabling, but research has not been able to find tangible evidence on long-term brain changes when properly administered.

What remains unknown is why electroconvulsive therapy is effective. A plethora of studies show the neurochemical correlates of this treatment and its relation to the anti-depressant effect, yet none are conclusive. Richard Abrams has studied ECT for years and discusses a wide variety of reasons for its effectiveness in his revised edition of Electroconvulsive Therapy. For a person who has studied this treatment for 50 years, he concludes that there is nothing more to say about ECT's mechanism of action than he did when ECT was first widely used.

Electroconvulsive therapy is "the induction of a seizure (fit) for therapeutic purposes by the administration of a low frequency electrical stimulus shock" (1). Why does a seizure, which creates random activity in the brain, able to relieve depression and other mental conditions? What does the electricity do to one's brain? Abrams' interpretation of its effectiveness, partially based on his own work and the interpretations of many other researchers, is that "the mechanism of the anti-depressant effect remains unknown and probably involves several interacting neurotransmitters. It seems that ECT affects various neurotransmitters and neuromodulators and that the interactions among these systems result in the neuroendocrine changes observed following an ECT course" (2).

Researchers, such as Abrams, believe that ECT changes the inactive neurotransmitter systems involved those suffering from depression. However, this claim is unsatisfying because of its vagueness, and is most likely due to the fact that the etiologies of these "disorders" are unknown. Furthermore, ECT has merits when used for a wide range of depressive disorders, notably psychotic depression and bipolar disorder, as well as catatonia (mental numbness), schizophrenia, and schizoaffective disorders (3). There are several plausible reasons as to why these mental conditions result, but they are too generalized and vague. In addition, there exists no coherent generalized neurochemical theory of action of ECT, although it remains efficacious for these states. Moreover, since the mode of action is unknown in these mental states, the discovery of the mechanism of ECT is that much more difficult to assess.

The most common neurotransmitter systems involved in depression are the dopamine, norepinephrine, and serotonin systems. These systems are also involved in other psychiatric conditions, and include a long list of neurochemical correlates. It ranges from endorphins, enkephalins and prolactin, to GABA, glutamate and acetylcholine correlates. All of these systems in some way or another are involved in the behavioral manifestations of psychiatric illness, yet researchers do not know which systems are more involved with depression, than depression with psychosis. If this is unknown, then certainly the mechanism of action will not make sense, especially if there are multitudes of chemicals involved. The excessive amount of possible neurochemical correlates makes it difficult to sort out which chemicals are normal and which relate to the mental illness. Complexity of the system doubles when illnesses become comorbid.

The etiology of major depression for instance, hypothesizes it occurs because of a lack of activity in neurotransmitter systems (dopamine, norepinephrine, serotonin) (5) Some argue that the ECT-induced seizures create an upsurge of activity in the brain, and therefore increase any or all of these neurotransmitters, resulting in an elevated mood (4). For the other mental conditions, such as schizophrenia, ECT increases the prefrontal cortex activity, which may be low in these patients (1). For those in a catatonic state, ECT revives their stupor. How? Researchers do not know. Their best hypothesis or guess would say, 'Electrical stimulation in the brains of catatonics, creates more activity in the brain. This neuro-stimulation and activation may have allowed for involuntary communication within the brain, and therefore the automatic reconnection of the mental processes, and ultimate recovery'. Clearly, this is just as vague as 'ECT induces activity in the areas of the brain that are inactive in those who are depressed', or schizophrenic. If science knew the mechanism of these psychiatric conditions, then the mode of action for ECT would not be as vague. Similarly, if science knew the action of ECT, the mechanisms for psychiatric conditions of which ECT is effective could be insightful as well.

ECT is arguably superior to all other forms of treatment, especially for depression (6). Nevertheless, none of the studies tells us why. If there was a coherent theory for each of these mental conditions, which psychiatry and society labels illness, then the mechanism of action of ECT would be something more than a generalized statement about the reactivation of the brain and increase in neurotransmitter systems.

It is possible that chronic ECT administration is effective because it changes gene expression in those suffering from a mental health condition, but none of the literature discusses this in detail. ECT may strengthen the second messenger systems in these people and allow for a re-alteration in gene expression, which serves to increase neurotransmission and create an anti-depressant effect or "anti-schizophrenic effect". Furthermore, relapse in these people may occur because the ECT treatment ends, and what was once re-altering these genes, is no longer. Ending treatment may cause re-re-alteration in genes that serves to bring the patient back to his original state of depression.

We must assume that the brain's activity manifests itself in behavior concerning these mental conditions. For example, the reason we know anti-depressant medication works, is because it induces activity in the neurotransmitter systems that are low. One concludes therefore, that a dopamine agonist, which increases dopamine activity and has a positive effect on mood, must be lacking in a person with severe depression. Hence, this treatment becomes effective. The same goes for ant psychotic drugs as well. Presumably, if these medications (SSRI's, tricyclic anti-depressants, psychotropics) work for depression and schizophrenia for instance, then ECT must have the same mechanism of action. Clearly, some studies show this, while others do not. It follows the general rule of halves. In half of the subjects, ECT shows an increase of these systems, and in the other half, ECT does not increase activity. So why does it work? Aside from "spotty" memory loss, "transient" cognitive impairment and possible death from ECT, which is not very scientifically credible (2), there is no conclusive evidence for the effectiveness of ECT. Yet, it is a widely used treatment and has far higher success rates than any other form of treatment, including sham ECT (2).
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The fact of the matter is that we do not understand ECT's mode of action. But then, we are no worse off with regard to ECT than in our lack of understanding of the mode of action of psychoactive drugs, or behavior modification, or psychoanalysis, or psychotherapy. Max Fink, M.D., an expert on ECT states, and commentator in Abrams' book states, "I believe we actually know more about the effects of induced seizures in man than we do about the effects of psychoactive drugs, and a concerted effort at research into the mode of action of ECT would be particularly rewarding in our understanding of mood disorders, psychosis, brain function, and behavior" (2).

Agreeable? Yes. If science knew more about the action of ECT then it would certainly help in understanding the mechanisms involved in the conditions for which it works. However, if the field knows more about the effects of seizures on psychiatric conditions than drugs, the literature does not examine it. Moreover, if the field knows more about why ECT is effective, it is not discussed either. The book, designed for clinicians, researchers, students, administrators, and patients, does discuss "possible neurochemical correlates". Even then, the chemicals overlap from mental condition to mental condition, and from person to person. Therefore, science still does not know what takes place in the brain to account for its effectiveness. Research knows that it is effective, but not how or why.

There must be other observations to make better sense of ECT treatment. Perhaps there is a final common pathway for all of these neurochemical correlates, and discovering this would lead to the answer of why electricity helps patients. If neurotransmitters went to one area of the brain, the end of this pathway, then plausibly ECT may activate this area. This would lead to an effective treatment. ECT may activate gene replication and create cells that were once not there. Although unlikely, perhaps ECT alters just one mutated gene that caused the mental illness. Brain activation with ECT may switch the mutation, in the end helping the patient. As one can see, it is hard to come up with plausible explanations of why this treatment is effective. It would make sense to find out why the diseases take place, then examine the treatment. However, one way is not better than the other is since discovery would lead to insight in both cases.

The interpretations of the efficaciousness of ECT do not fit very well into the problem of these mental conditions. This is because there is not a "depression gene" or any other. There is not one system serving as the culprit of this "illness". If there is no firm theory for depression, or schizophrenia than how does one expect there to be a profound interpretation of ECT? Abrams put it well when he said "modern theories of the action of ECT- even as formulated by sophisticated investigators...have not surpassed in conceptual elegance the 18th century claim that things burned because they contained phlogiston; ECT awaits its Lavoisier" (2). Indeed, ECT awaits its father of psychopharmacology, so does depression, and every other mental illness. How long are we going to sit on the idea that the effects of ECT are unknown and that it probably involves several neurotransmitter and neuromodulator systems acting together? Research must continue to study the mechanisms of action of ECT and severe mental illness in hopes of coming to a definitive conclusion about why they occur, and how treatment is effective.

 

References

1)Electroconvulsive therapy for schizophrenia

2) Abrams, R. (1997). Electroconvulsive Therapy. (3rd ed.). New York: Oxford University Press.

3)Electroconvulsive Therapy

4)ECT and Receptor Function

5)Depression FAQ

6)All about ECT- Electroconvulsive Therapy

 

Recommended Reference

7)ECT On-line: Some ECT links

 

 

Comments made prior to 2007


As I reviewed your article for information on ECT I found some dubious information. The article purports that depression is caused by an under-activity of neurotransmitters, but I learned in psychology classes time and again that the opposite is true. This of course, is why there are prescription medications such as SSRI's, which work by collecting some of the excess serotonin in a depressed individual's brain. Correct me if I'm wrong, I just wanted to clarify this so as to avoid a spread of incorrect information. Thank you for your time ... Jessica Mahoney, 15 July 2004

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