Brain Stimulation Wars

href="http://www.researchblogging.org"> alt="ResearchBlogging.org"
src="http://www.researchblogging.org/images/rbicons/ResearchBlogging-Medium-White.png"
height="50" width="80">Just as
we learn of favorable studies about rTMS (see yesterday's post on this blog), studies that suggest
that ECT could be surpassed, the ECT camp fires again.  A new
study by Sackeim indicates that a new form of ECT is highly effective,
with lower negative impact on cognition.  The difference is in
the length of the electrical pulse.  They use what they call
an ultrabrief pulse (0.3 millisecond), as opposed
to the traditional 1.5 millisecond pulse.

href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B8JBG-4S79T61-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=757ecfb979ffeea3b40d0e89a88b0371">Effects
of pulse width and electrode placement on the efficacy and cognitive
effects of electroconvulsive therapy

Harold A. Sackeim PhD, Joan Prudic MDa,
Mitchell S. Nobler MDa, Linda Fitzsimons RNa, Sarah H. Lisanby MDa,
Nancy Payne CSWa, Robert M. Berman MD, PhDa, Eva-Lotta Brakemeier MAa,
Tarique Perera MDa and D.P. Devanand MD

Brain Stimulation

Volume 1, Issue 2, April 2008, Pages 71-83

Background

Although electroconvulsive therapy
(ECT) in major depression is effective, cognitive effects limit its
use. Reducing the width of the electrical pulse and by using the right
unilateral electrode placement may decrease adverse cognitive effects,
while preserving efficacy.

Methods

In a
double-masked study, we randomly assigned 90 depressed patients to
right unilateral ECT at 6 times seizure threshold or bilateral ECT at
2.5 times seizure threshold, using either a traditional brief pulse
(1.5 milliseconds) or an ultrabrief pulse (0.3 millisecond). Depressive
symptoms and cognition were assessed before, during, and immediately,
2, and 6 months after therapy. Patients who responded were monitored
for a 1-year period.

Results

The final
remission rate for ultrabrief bilateral ECT was 35%, compared with 73%
for ultrabrief unilateral ECT, 65% for standard pulse width bilateral
ECT, and 59% for standard pulse width unilateral ECT (all P
< .05 after covariate adjustment). The ultrabrief right
unilateral
group had less severe cognitive side effects than the other three
groups in virtually all primary outcome measures assessed in the acute
postictal period, and during and immediately after therapy. Both the
ultrabrief stimulus and right unilateral electrode placement produced
less short- and long-term retrograde amnesia. Patients rated their
memory deficits as less severe after ultrabrief right unilateral ECT
compared with each of the other three conditions (P
< .001).

Conclusions

The
use of an ultrabrief stimulus markedly reduces adverse cognitive
effects, and when coupled with markedly suprathreshold right unilateral
ECT, also preserves efficacy. (ClinicalTrials.gov number, NCT00487500.)

Note the following: random, doulbe-blind design (good); 90 patients
(fair); 1-year follow up (good); cognitive effects assessed by patient
ratings (not so good).



Note that an even longer follow-up period would be good, and that, in
order to be convincing, I would want to see comprehensive
neuropsychological testing performed periodically on all participants.



As in all such studies, we really need to see replication in order to
believe it.  This particular study is something that we all
want to believe, but wishing does not make it so.  In fact,
that kind of wishing makes it particularly important to be cautious in
interpreting the results.  The fact that it is plausible at
face value is another reason to be cautious.



I am not faulting the authors.  It is expensive to have a
really large, (and preferably) multi-center study.
 Neuropsychological testing is particularly expensive.
 It makes sense to do a more limited study first, to see if
the expense of a more definitive study has a chance of being
worthwhile.  



Although ECT is highly effective, the cognitive problems are a major
impediment to wider implementation.  See this study ( href="http://www.cma.ca/index.cfm/ci_id/53071/la_id/1.htm">The
long-term impact of treatment with electroconvulsive therapy on
discrete memory systems in patients with bipolar disorder)
for a full discussion.  The authors conclude that their
findings "raise the question of whether certain strategies that
minimize cognitive dysfunction with ECT should be routinely employed in
this patient group."  Until now, it has not been clear exactly
what those strategies might be.  



I will be interested to see what comes of this.   href="http://en.wikipedia.org/wiki/Antipsychiatry" rel="tag">Antipsychiatry
groups have long derided href="http://en.wikipedia.org/wiki/Antipsychiatry#Electroconvulsive_therapy"
rel="tag">Electroconvulsive Therapy in particular.
 Even unbiased persons have a hard time accepting the
rationale and clinical utility of ECT.  If it is possible to
further reduce the adverse effect burden, it is possible that public
acceptance eventually will improve.  



For this to happen, though, it will be necessary to avoid overplaying
the technical advances, and to communicate clearly and openly the
implications of new developments.  Some persons have gotten to
be skeptical of announcements of techincal advances in medical
treatments.  And rightly so, as demonstrated by the experience
with Vioxx and other supposedly new-and-improved treatments.  





formal citation:

title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.aulast=SACKEIM&rft.aufirst=H&rft.au=H+ SACKEIM&rft.au=J+PRUDIC&rft.au=M+NOBLER&rft.au=L+FITZSIMONS&rft.au=S+LISANBY&rft.au=N+PAYNE&rft.au=R+BERMAN&rft.au=E+BRAKEMEIER&rft.au=T+PERERA&rft.au=D+DEVANAND&rft.title=Brain+Stimulation&rft.atitle=Effects+of+pulse+width+and+electrode+placement+on+the+efficacy+and+cognitive+effects+of+electroconvulsive+therapy&rft.date=2008&rft.volume=1&rft.issue=2&rft.spage=71&rft.epage=83&rft.genre=article&rft.id=info:DOI/10.1016%2Fj.brs.2008.03.001">SACKEIM,
H., PRUDIC, J., NOBLER, M., FITZSIMONS, L., LISANBY, S., PAYNE, N.,
BERMAN, R., BRAKEMEIER, E., PERERA, T., DEVANAND, D. (2008). Effects of
pulse width and electrode placement on the efficacy and cognitive
effects of electroconvulsive therapy. style="font-style: italic;">Brain Stimulation, 1(2),
71-83. DOI: href="http://dx.doi.org/10.1016/j.brs.2008.03.001">10.1016/j.brs.2008.03.001