EDITORIAL

Mechanisms of ECT
Reviewing the Science and Dismissing the Myths
Pascal Sienaert, MD, PhD

The main claim of the physical approach, that is the assumption that mental disorders are
dependent on physiological changes, is that it is a useful working hypothesis. It has made great
advances and looks like making more.

Sargant and Slater

An Introduction to Physical Methods of
Treatment in Psychiatry. 19441

E l ectroconvulsive therapy (ECT) is the oldest biological treatment in psychiatry still available. Al-
though critics claim that it is (still) performed without any knowledge of how it works,2 from its
birth, the use of ECT was based on theory and scientic facts. In the early 1930s, Medunas idea of
eliciting brain seizures was based on a theory of a biological antagonism: the assumption that psy-
chotic symptoms and epilepsy could not coexist. The facts: In neuropathological studies, Meduna
had shown that in the horn of Ammon of patients with dementia praecox, there was a paucity of glial
cells, whereas in patients with epilepsy, glial cells were increased.3 Inducing seizures in psychotic
patients, he theorized, would restore the number of glial cells and reverse the symptoms of dementia
praecox.3 Time has proven him right. Neurogenesis, gliogenesis, and neuronal plasticity hypotheses
are among the most conclusive theories about ECTs mechanism of action.4,5
The past decades have seen some major efforts to summarize the state of knowledge of ECTs
working mechanism and to encourage its further study. In 1972, a National Institute of Mental Health
conference was held in Puerto Rico, the proceedings of which were published in the 1974 volume
Psychobiology of Convulsive Therapy.6 Based on the biogenic amine hypothesis, postulating that de-
pression is caused by a functional deciency of catecholamines, particularly norepinephrine,7
neurotransmitters were an important focus. It is evident, however, that neither complex psychiatric
diseases nor the mechanism of action of their treatments can be explained by an imbalance in 2 or
3 chemical substances. At a second conference, held in New Orleans in 1978, the proceedings of
which were not published, Ottoson and Fink urged the eld to shift attention toward neuroendocrine
theories8 (Fink, personal communication, 2013). Some years later, in a special issue of this journal,
Fink and Nemeroff postulated the existence of a hypothalamic peptide that regulates mood and vegetative
functions, antidepressin, the production of which was supposed to be stimulated by repeated seizures.9 The
same year, Sidney Malitz and Harold Sackeim edited the proceedings of a conference held in 1985 in New
York,10 presenting more than 25 papers on neurochemical, neuroendocrinological, neurophysiological, and
neuropsychological aspects of ECT.
More recently, theorizing about pathogenesis and mechanisms of treatment effects has focused on
disturbances in cellular plasticity cascades leading to aberrant information processing in critical circuits11
and genetics.12,13 It is a tempting thought that ECT restores the neurocircuitry, via an inuence of brain
growth factors, so neurotransmitters can act properly. Even more tempting is the idea that both the
effects and the transient adverse effects of ECT could be explained by these same mechanisms. The fact
that cognitive (adverse) effects are not essential for the therapeutic effect, that is, that effective ECT

From the ECT Department and Department of Mood Disorders, University Psychiatric Center KU Leuven, Campus Kortenberg, Belgium; and Faculty of
Medicine, Catholic University of Leuven, Leuven, Belgium.
Received for publication January 22, 2014; accepted January 23, 2014.
Reprints: Pascal Sienaert, MD, PhD, ECT Department and Department of Mood Disorders, University Psychiatric Center KU Leuven; and Catholic University
Leuven, Campus Kortenberg, Leuvensesteenweg 517, Kortenberg, Brabant, 3070 Belgium (email: pascal.sienaert@pandora.be;
pascal.sienaert@uc-kortenberg.be).
The author has no conict of interest or nancial disclosures to report.
Copyright 2014 by Lippincott Williams & Wilkins
DOI: 10.1097/YCT.0000000000000118

Journal of ECT Volume 30, Number 2, June 2014 www.ectjournal.com 85

Copyright 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

can be performed without measurable cognitive adverse effects,1416
does not preclude the possibility that the therapeutic mechanism
shares some features with the transient cognitive effects. An initial
phase of increased neurogenesis, therapeutic efcacy, and cogni-
tive adverse effects can be followed by a phase during which
new neurons succeed in making functional connections, resum-
ing cognitive function.5,17 Recent data suggest that the inhibition
of the expression of genes that play an important role in regulat-
ing neuronal plasticity during memory formation and consolida-
tion, via epigenetic mechanisms, might provide an explanation
for cognitive adverse effects observed after ECT.13
In the past 25 years, the Journal of ECT published 3 special
issues devoted to the mechanisms of ECT: one, in 1989, edited by
Harold Sackeim18; and two, in 1998 and 1999, edited by Bernard
Lerer,19,20 reecting that the quest did not cease. It is true that an
acceptable and fully explanatory and convincing theory still needs
to be postulated, to cite Endler and Persads The Myths and the
Realities.21 This issue presents a small but signicant insight in
the endeavors that have been undertaken in the past decades.
The reader will nd a wealth of papers reviewing the science
and dismissing the myths. This issue summarizes both past and re-
cent data that show a marked progression in the insight in ECTs
mechanisms of action. It shows that there is neither a poverty of
theories nor a paucity of data. Electroconvulsive therapy produces
various changes, and, as Seymour Kety stated 40 years ago, The
difculty lies not in demonstrating such changes, but in differ-
entiating between those which are more fundamental and
those which are clearly secondary, and also in attempting to
discern which of the changes may be related to the important
antidepressive or amnestic effects and which are quite irrele-
vant to these.22 As of today, there is no denitive unied the-
ory on how ECT works, on how cognitive adverse effects are
explained, and on how both are related. This is, however, not
a sign of a failing science but of a continuously growing insight
in the complex mechanism underlying the most effective and
indispensable treatment in psychiatry.
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3. Fink M. Catatonia and ECT: Medunas Biological Antagonism
Hypothesis Reconsidered. World J Biol Psychiatry. 2002;3:4.
4. Ongur D, Heckers S. A role for glia in the action of electroconvulsive
therapy. Harv Rev Psychiatry. 2004;12:253262.
5. Bouckaert F, Sienaert P, Obbels J, et al. ECT: its brain enabling effects.
A review of electroconvulsive therapyinduced structural brain
plasticity. J ECT. 2014;30:143151.
86 www.ectjournal.com
Copyright 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Journal of ECT Volume 30, Number 2, June 2014
6. Fink M. Psychobiology of Convulsive Therapy. Washington: V. H.
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2014 Lippincott Williams & Wilkins