COMMENTARY
Advances in Technique and Understanding Mechanisms
of Action
Adding to the Evidence Base in Electroconvulsive Therapy (ECT)
Charles H. Kellner, MD
A s we come to the end of the year commemorating the 80th
anniversary of the invention of electroconvulsive therapy
(ECT), JECT continues to lead the way in providing a forum
for the latest in clinical and basic research on ECT. The follow-
ing three articles from the current issue exemplify additions to
the evidence base of refinements to ECT technique and our un-
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derstanding of mechanism(s) of action.
The study of Lemasson et al1 is a multinational, retrospec-
tive comparison of stimulus dosing methods in a cohort of over
500 patients. It is significant for the size of the study popula-
tion and the collaboration among investigators in different
countries, as well as for the actual study findings. Those find-
ings replicate previous work elucidating the variables that
contribute to seizure threshold (ST) in patient populations,
while adding new data about the comparative precision of dose
finding methods. Somewhat ironically, we may know more
about how to find an individual patient's ST than what to do
with the information. That is understandable, because research
correlating ST, subsequent dosing in the treatment series, and
clinical outcomes requires large, prospective studies that are
complex and hard to get funded. In general, it is now widely
accepted that right unilateral electrode placement should be
dosed more liberally in relation to ST than bilateral placements.
Further refinements in our knowledge, leading to more person-
alized ECT, will come with ongoing investigations that can cor-
relate clinical response to technical factors such as ST and
relation of subsequent dosing to ST. Lemasson and colleagues
are to be congratulated for their substantial contribution to the
evidence base.
Bozymski et al2 report their innovative work-around to
address a shortage of commercially available intravenous
caffeine for seizure augmentation in ECT. This is both instruc-
tive from a pharmacy perspective and because it serves to re-
mind us of this specific seizure-enhancing technique. Caffeine
augmentation, a fairly common feature of ECT practice 20 to
30 years ago, largely fell by the wayside more recently, but
may now be coming back. Its use is based on the notion that
seizure enhancement (longer duration of both motor and
EEG seizure) leads to better, and perhaps quicker, clinical re-
sponse. The hope that caffeine would also lower ST, and
thereby allow the use of lower stimulus doses, does not seem
to have been born out. The authors also remind us of the
From the Department of Electroconvulsive Therapy (ECT), New York Com-
munity Hospital, Brooklyn; and Department of Psychiatry, Icahn School of
Medicine at Mount Sinai, New York, NY.
Received for publication September 23, 2018; accepted September 24, 2018.
Reprints: Charles H. Kellner, MD, New York Community Hospital, Brooklyn,
NY (e‐mail: ckellner@nych.com).
Dr Kellner has received grant funding from the National Institute of Mental
Health. He receives payments/honoraria from UpToDate, Psychiatric
Times, and Cambridge University Press.
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/YCT.0000000000000552
Journal of ECT • Volume 34, Number 4, December 2018
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
beneficial additional effect of caffeine, namely, headache pro-
phylaxis. The Bozymski et al data clearly replicate the earlier
findings of increased seizure duration with caffeine, along
with an acceptable safety profile. Similar to the situation with
ST discussed previously, the clinical significance and impli-
cations of these findings is less clear. Do we know the effect
of lengthening the seizures in an individual patient from,
say, 30 to 40 seconds? Without well-designed, prospective
clinical trials, it remains a matter of speculation whether mod-
est increases in seizure length lead to meaningfully improved
patient outcomes. A similar situation exists regarding the use
of flumazenil to reverse on-board benzodiazepines, which are
assumed to prevent, or shorten, ECT seizures. It seems intui-
tively obvious that such an intervention would lead to better
ECT outcomes, but this remains to be proven. Finally, yet an-
other technical situation related to seizure length is the use of
propofol as an induction agent. Propofol has been shown to
clearly decrease seizure length compared with other anes-
thetics, but this has never been proven to be detrimental to
antidepressant efficacy. As ECT practitioners, we can make
interesting, safe pharmacological additions to the ECT anes-
thesia experience, but whether they actually improve clinical
efficacy remains to be proven.3
Xia et al4 report the results of a clinical trial using proton
magnetic resonance imaging spectroscopy to measure pre-
frontal gamma-aminobutyric acid (GABA) levels in patients
with schizophrenia, before and after treatment, either with
ECT plus antipsychotic medications or antipsychotic medications
alone. Their main findings are decreased baseline GABA levels in
patients compared with controls, and greater posttreatment in-
crease in GABA in those patients treated with ECT plus medica-
tions. These results are consistent with other work showing
GABA enhancement with ECT treatment, and are particularly
intriguing because of the possible interplay between an inhib-
itory neurotransmitter and the anticonvulsant hypothesis of
the mechanism of action of ECT. They also serve to remind
us that outside of the United States, schizophrenia is the lead-
ing indication for ECT, not depression.
Taken together, these 3 studies illustrate the vibrancy and
range of clinical research in ECT today. Of course, basic labo-
ratory studies, using the electroconvulsive shock paradigm, are
also thriving in many academic centers. Such clinical and basic
research activity is vitally important because, even as the clin-
ical world of ECT grows and becomes more integrated into main-
stream psychiatric medicine, ECT continues to be attacked by
antipsychiatry interests. Particular themes of these attacks are
the cognitive effects of the treatment and the fact that we do not
fully understand the exact mechanism(s) of action by which
ECT exerts its antidepressant and antipsychotic effects. New clin-
ical research data, as exemplified by the above three studies, pro-
vide the best response to parry the often inaccurate and biased
critiques of ECT; they attest to the ongoing, concerted efforts of
our field to provide patients with the safest, best tolerated, most
www.ectjournal.com 209
Commentary
refined forms of ECT. Our knowledge of how and why ECTexerts
its typically dramatic, beneficial effects on severe mood and psy-
chotic disorders is growing at a very rapid rate.
REFERENCES
1. Lemasson M, Rochette L, Galvão F, et al. Pertinence of titration and
age-based dosing methods for electroconvulsive therapy: an
international retrospective multicenter study. J ECT. 2018;34:
220–226.
210 www.ectjournal.com
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
Journal of ECT • Volume 34, Number 4, December 2018
2. Bozymski KM, Potter TG, Venkatachalam V, et al. Caffeine sodium
benzoate for electroconvulsive therapy augmentation. J ECT. 2018;
34:233–239.
3. Kellner CH, Bryson EO. Electroconvulsive therapy anesthesia
technique: minimalist versus maximally managed. J ECT. 2013;29:
153–155.
4. Xia M, Wang J, Sheng J, et al. Effect of electroconvulsive therapy on
medial prefrontal g-aminobutyric acid among schizophrenia: a
proton magnetic resonance spectroscopy study. J ECT. 2018;34:
227–232.
© 2018 Wolters Kluwer Health, Inc. All rights reserved.