Theories on Mechanism of Action of

Electroconvulsive Therapy

Sandeep Grover, Surendra Kumar Mattoo, Nitin Gupta

Abstract. Electroconvulsive therapy (ECT) is a useful yet controversial mode of treatment. Despite being in use for over 70 years, its mechanism of action (MOA) is still not clearly understood. Various theories on MOA of ECT have been proposed over the years. These have included looking at psychological, neurophysiological, neurochemical, neuroendocrine, and neuropeptides mechanisms.An attempt is made here to review the existing literature on the MOA of ECT in a historical perspective. Various theories are discussed in context of the available pre-clinical and clinical research evidence with highlighting of the methodological issues and looking at the relevance of each theory.In summary, there is no single theory that satisfactorily explains the MOA of ECT in various psychiatric illnesses. The need for properly

designed, ethically sound pre-clinical and clinical studies is highlighted (German J Psychiatry 2005; 8: 70-84).

E-mail: [email protected]

Dear,

Two articles regarding the mechanism of action of ECT (for mood disorders)

Regards,

M. Arts

Article:

Frais AT. Electroconvulsive therapy: a theory for the mechanism of action. J ECT 2010 Mar;26(1):60-1.

Cases of memory deficits after electroconvulsive therapy (ECT) have been widely reported particularly short-term memory and to a lesser extent, long-term and autobiographical memory. Explanations for the mechanisms of ECT action have largely been limited to studies of the effect on brain metabolism, neurochemistry, and areas of the brain such as the hippocampus and frontal lobes. However, passing a current of electricity through the brain is clearly a holistic treatment, and consequently, a holistic theory may offer a better understanding of ECT action. Because of its effect on memory systems both positive and negative, it is possible that aspects of memory function could hold the key in explaining how and why successful ECT treatment functions. It will be argued that successful ECT treatment is effective because it facilitates and restores the function of specific memory systems that are deficient in the course of a severe depressive episode. It is these memory systems that link a person to the very essence of their existence and personal identity.

Article:

Perrin JS et al. Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder. PNAS 2012;109(14): 5464-5468.

To date, electroconvulsive therapy (ECT) is the most potent treatment in severe depression. Although ECT has been successfully applied in clinical practice for over 70 years, the underlying mechanisms of action remain unclear. We used functional MRI and a unique data-driven analysis approach to examine functional connectivity in the brain before and after ECT treatment. Our results show that ECT has lasting effects on the functional architecture of the brain. 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; the patients’ mean scores on the Montgomery Asberg Depression Rating Scale pre- and posttreatment were 36.4 (SD = 4.9) and 10.7 (SD = 9.6), respectively. The findings reported here add weight to the emerging “hyperconnectivity hypothesis” in depression and support the proposal that increased connectivity may constitute both a biomarker for mood disorder and a potential therapeutic target.

Having discussed this at length with Neurologists, Psychiatrists, and Patients who have undergone ECT; I must agree that the mechanism of action for what makes this treatment method successful with severely depressed patients, has yet to be identified.

The hyperconnectivity hypothesis is interesting. Regarding hypotheses, allow me to refer to a review paper I wrote in Canadian Journal og psychiatry 1911.

Jpn J Pharmacol. 1999 Jul;80(3):185-9.

Mechanism underlying the therapeutic effects of electroconvulsive therapy (ECT) on depression.

Ishihara K, Sasa M.

"5-HT1A-receptor sensitization may be important for explaining the effectiveness of ECT, as this change induces a decrease in the number of 5-HT2A receptors that are elevated in depressive patients. Facilitation of neurotransmitter releases due to 5-HT3-receptor sensitization by ECT may also play an important role in effective treatment of depressive patients refractory to therapeutic drugs."

The June 2nd  edition of the Psychiatric News discusses the risks and  benefits of ECT.

Well, I'm pretty sure it has nothing to do with a receptor. This kind of thinking of antidepressant receptors or neurotransmitter abnormalities has been around for over 60 years, defining the whole field of pharmacology. But all billions spent in drug development have led to no new therapeutic modalities. The newest drugs actually seem to resemble the earliest drugs, again attacking all the possible monoamines and a variety of receptors.

What is new is the advent of the rapid-acting antidepressant drugs, such as ketamine. The method of action in these is still as unknown, but resembles similar time scales as ECT. It is very likely, that the mechanism behind the action of these "shock" therapies is an innate mechanism in the brain, and it is simply not activated by a drug binds to any spesific receptor. The response of the brain to the drug or electricity is what makes it work. Disrupting the already messed up homeostatic state and possibly triggering a more trophic state, providing a basis for the formation of new neuronal connections. With repeated treatment, therapy and time passing, this might then lead to the end of depression.

Originally it was observed that people with epilepsy were less depressed after a discharge so researchers tried to create this kind of electric impulse chaos in artificial way and it worked. 

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