January 28, 2011: Media Release:
FDA REPORT on ELECTROSHOCK UNDER-ESTIMATES MORTALITY AND
MEMORY LOSS
Professor John Read (University of Auckland, New Zealand) has
submitted to the FDA ‘Commentary’ of the FDA’s 150 page ‘Executive Summary’
report – released on the eve of its hearings about Electroshock Therapy (Jan
27-28).
Dr Read had previously submitted a 2010 research
literature review, co-authored with Professor Richard Bentall (University of
Liverpool), concluding that ECT had no benefits beyond the treatment period,
did not prevent suicide and caused long-lasting, sometimes permanent memory
dysfunction. Read, J., Bentall,
R. (2010). The effectiveness of electroconvulsive therapy: A literature review.
Epidemiologia e Psychiatria Sociale, 19, 333-347.
Effectiveness
The five page Commentary (available on request:
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) states, in relation to effectivness,‘The FDA staff seem
to have conducted a comprehensive review of the available research. They reach
broadly similar conclusions to that of our own recent review’, namely:
‘Little evidence exists supporting the long-term
effectiveness of ECT’
(FDA Report))
Suicide Prevention
The belief that ECT somehow prevents suicide has long
been a central plank of claims that it is effective made by ECT proponents. The
Commentary notes that the FDA reports no studies at all in support of this
claim. There are none. There were,
however, 43 individual submissions to the FDA citing suicidality as an adverse
effect (p 68).
Deaths
The FDA report devotes only half a page to this issue.
A claim first made by the American Psychiatric
Association (2001) is repeated verbatim by the FDA: ‘mortality rate of 1:10,000
patient, or 1:80,000 treatments’.
Our literature review (Read & Bentall, 2010) found
numerous studies with mortality rates far in excess of that claimed by the APA
and reproduced, rather uncritically, by the FDA.
103 deaths were reported to the FDA in individual
submissions “The FDA report appears to have significantly underestimated the
mortality rate of ECT.”
Memory Loss
The FDA report fails to include the best designed study
to date assessing autobiographical memory.
Despite repeated claims, for 50
years, that ECT is safe, the first large-scale prospective study of cognitive
outcomes following ECT did not occur until 2007.
Prominent ECT advocate Harold
Sackeim, found that autobiographical memory was significantly worse than
pre-ECT levels six months later. At both times the degree of impairment was
significantly related to the number of shocks.
[The Sackeim study was formally submitted
to the FDA, by JR, on Dec. 30, 2010, with the Read & Bentall literature
review – which is also uncited]
A New Zealand Government report, commissioned
by the Ministry of Health concluded that “ECT may permanently affect memory”
(Ministry of Health, 2004) and bemoans the “slowness in acceptance by some
professional groups that such outcomes are real and significant in people’s
lives”.
Even the 2001 APA Report has acknowledged that “In some
patients the recovery from retrograde amnesia will be incomplete, and evidence
has shown that ECT can result in persistent or permanent memory loss”.
The Commentary concludes: “The FDA report has grossly
underestimated the duration of the memory deficits caused by ECT”.
‘Subjective’ Memory Loss
“The FDA report also repeats the claim that much of the
memory loss is related to the depression rather than to the ECT, using the term
‘subjective memory loss’ employed by by ECT proponents to promote this
hypothesis. Our review points out that this oft-made claim has been repeatedly
demonstrated to be unsubstatantiated.”
~~~~~~~~~~~~~~~~~~~~
COMMENTARY ON FDA REPORT PREPARED
FOR MEETING OF THE NEUROLOGICAL DEVICES PANEL ON ELECTROSHOCK THERAPY AND
DEVICES - JANUARY 27-28, 2011
Submitted to FDA January
26,2010
Professor John Read,
University of Auckland, New Zealand. January 26, 2011.
Note: This commentary focuses
primarily on the research using sham/simulated ECT vs real ECT methodology –
which is unanimously agreed to be the best available design to control for the
powerful placebo effects associated with ECT. See Read and Bentall (2010).
EFFECTIVENESS
FDA staff seem to have conducted a comprehensive review of the available
research. They reach broadly similar conclusions to that of our own recent
review, namely:
Depression (the most
commonly targeted diagnosis – especially depressed older women):
‘Evidence for the
effectiveness of ECT exists only for acute effects’ (p 36)
‘Little evidence exists
supporting the long-term effectiveness of ECT’ (p 37)
‘For depression, after one
month, the limited available evidence does not support the conclusion that that
ECT is more effective than sham’.
Our own literature review concurred,
i.e. ECT has no beneficial effects beyond the actual treatment period. We
found, however, that even those short term advantages over sham ECT were ‘only for some patients, on some measures, sometimes
perceived only by psychiatrists and not by other raters’.
Schizophrenia (for which ECT was invented, –
currently the second most common diagnosis of ECT recipients)
‘ECT for Schizophrenia: In ECT
vs. sham comparisons, the effectiveness of ECT and sham were not found to be
significantly different.’ (p 42)
Prevention of Suicide
The belief that
ECT is life-saving, primarily through its supposed ability to prevent suicide,
has long been a central plank of claims that it is effective made by ECT
proponents. (For recent examples see statements by Drs Kellner and Fochtman in NYTimes article Jan
23, 2011.)
The FDA reports no
studies at all on this issue.
It claims nevertheless,
in a Table (p 72), that there is ‘No
indication of increased risk in the literature, and some suggestion that risk
may decrease’.
The use of the
term ‘may’ is far more tentative than the categorical assertions of ECT
proponents.
Our review found
no properly designed studies supporting this claim, and two studies suggesting
an increased risk.
It appears that
this claim is particularly immune to the fact that there is no research
evidence to support it. The FDA should not repeat this unsubstantiated claim.
There were 43
individual submissions to the FDA citing suicidality as an adverse effect (p
68).
ADVERSE EFFECTS
In this area the conclusions of the FDA
report differ from our own conclusions somewhat.
Deaths
The FDA report devotes only half a page to this issue. (p
35-36).
A claim first made by the
American Psychiatric Association (2001) is repeated verbatim by the FDA: ‘mortality
rate of 1:10,000 patient, or 1:80,000 treatments’. (pp 35, 131)
Our literature review found numerous
studies with mortality rates far in excess of that claimed by the APA and
reproduced, rather uncritically, by the FDA. The FDA report itself cites one of
these; with a death rate of 79:10,000 (18 out of 2,279 patients), i.e. 79 times
greater than the APA claim:
‘Nuttall and
colleagues (2004) conducted a large retrospective review of ECT. They examined
2,279 patients who underwent 17,394 ECT treatments. Twenty-one patients (0.92%)
experienced a complication during their series of ECT (median number of
treatments = 7). Cardiac arrhythmias represented the majority of complications.
Although there were no occurrences of permanent injury or death immediately
after ECT, there were 18 deaths within 30 days of the last treatment.’ (p
36)
However the FDA report
goes on to state, despite one of the deaths being a cardiac arrest within two
days of ECT, that ‘… none were thought to be related to ECT’. The obvious, but
unasked, question here is ‘thought’ by whom?
Elsewhere the FDA
report correctly points out that: ‘Cardiovascular
complications are one of the most frequent causes of significant morbidity and
mortality associated with ECT (p
19).
The FDA also repeats the APA claim
that the mortality rate ‘is estimated to be approximately the same as the
rate associated with minor surgery’ (p 35). Even if this were true of an
individual administration of ECT (which is unlikely given the cardiovascular
and other complications specific to ECT) the claim ignores the rather obvious
fact that a course of ECT averages about eight adminstrations of the procedure,
and that the actual risk is, therefore, several times higher than an individual
procedure for each ECT recipient.
103 deaths were reported to the FDA
in individual submissions (p 68)
Two of the 151 incidents reported to
date by the Manufacturer and User Facility Device Experience (MAUDE) database
were deaths
The FDA report appears to have significantly underestimated
the mortality rate of ECT.
Memory Loss
Our review and the FDA concur on the
fact that the most common adverse effects are in the domain of memory loss.
‘There is clear evidence
that memory and cognitive impairment (i.e., orientation, retrograde memory,
anterograde memory and global cognitive function) occur both immediately after
administration of ECT and following a course of therapy
• The primary type of retrograde memory affected is autobiographical memory
• Estimated memory loss ranges from
29% - 79% (Rose et al., 2003)’ (p 22)
The two reports differ, however, on
the crucial issue of how long the memory dysfunction lasts. The FDA search of
the literature seems to be less comprehensive on adverse effects (eg deaths see
above) than for effectiveness.
For example, the FDA report fails to
include the best designed study to date assessing autobiographical memory. Despite repeated claims, for 50 years, that ECT is safe,
the first large-scale prospective study of cognitive outcomes following ECT did
not occur until 2007. Prominent ECT advocate Harold Sackeim, found that
autobiographical memory was significantly (p < .0001) worse than pre-ECT
levels both shortly after ECT (on average 4.4 days) and six months later. At
both times the degree of impairment was significantly related to the number of
shocks. Women and older people (both of whom are given ECT more frequently)
were particularly impaired. Even using a conservative definition of two
standard deviations worse than pre-ECT scores, 38 (12.4%) met the criterion for
‘marked and persistent retrograde amnesia’ (Sackeim et al., 2007).
[The Sackeim study was
formally submitted to the FDA, by JR, on Dec. 30, 2010, with the Read &
Bentall literature review – which is also uncited]
Similarly,
although the FDA report cites a literature review that ‘Estimated memory loss ranges from 29% - 79% (Rose et al., 2003)’ (p 22), the report fails to add that
the same review found a range for “persistent or
permanent memory loss” of 29% to 55%, with a weighted average of 38%.
A New Zealand
Government report, commissioned by
the Ministry of Health concluded that
“ECT may permanently affect memory” (Ministry of Health, 2004) and
bemoans the “slowness in acceptance by some professional groups that such
outcomes are real and significant in people’s lives”.
Even the 2001
APA Report has acknowledged that “In some patients the recovery from retrograde
amnesia will be incomplete, and evidence has shown that ECT can result in
persistent or permanent memory loss”.
the FDA report
has grossly underestimated the duration of the memory deficits caused by ECT.
‘Subjective’ Memory Loss
The FDA report
also repeats the claim that much of the memory loss is related to the
depression rather than to the ECT, using the term ‘subjective memory loss’
employed by by ECT proponents to promote this hypothesis. Our review points out
that this oft-made claim has been repeatedly demonstrated to be
unsubstatantiated. For example:
Another study (Neylan et
al., 2001), which acknowledged that “the memory loss for events
immediately preceding, during and after the treatment course can
be permanent”, found “no significant correlation between the change in
depression rating and the change in any of the 12 cognitive measures”. A recent
review concluded that “There is no evidence of a correlation between
impaired memory/cognition after ECT and impaired mood, much less a causal
relationship” (Robertson & Pryor, 2006).
The only large scale
prospective study found no relationship between severity of depression and 19
of the 22 cognitive measures employed (Sackeim et al.,
2007).
Neither of these
three studies are cited by the FDA report.
The FDA report fails
to acknowledge that even if there was a correlation, the causal relationship
might have been in the other direction. It can be depressing to lose one’s
memory.
MODALITY AND VOLTAGE:
A DILEMMA FOR THE FDA
Much of the FDA report
is, appropriately, taken up with comparing the effects of bi-lateral (ECT
administered across the brain from two electrodes) vs the effects of unilateral
ECT, and the effects of a range of voltages.
The findings,
consistent with many previous reports, are that bilateral and higher voltages
are more effective but that they also carry greater risk of adverse effects,
particularly memory and other cognitive dysfunction.
For example:
‘Bilateral electrode
placement is associated with a greater risk of cognitive impairment than
unilateral electrode placement, and when unilateral electrodeplacement is
utilized, high energy ECT dose is associated with a greater risk ofcognitive
impairment than low energy dose ECT’ (p 23).
‘Bilateral ECT is probably
more effective than unilateral’(p 36)
‘Increased electrical stimulus
above seizure threshold (ST) increases efficacy of unilateral ECT at the
expense of increased memory and cognitive impairment’ (p 36)
This creates a dilemma for
those charged with making regulatory decisions. ECT is at best minimally
effective and had serious adverse effects. The logical consequence of the
findings about bi-lateral treatment (which remains very common) would be to
prohibit any devices capable of administering this particularly damaging form
of ECT. However, the minimal effectiveness of ECT can only be improved at the
cost of further increasing the probability of memory loss, i.e by using
bi-lateral treatment.
This was not a dilemma for the
early pioneers of ECT. As our review points out:
In the 1940s it
was accepted that ECT worked precisely because it does cause brain damage and
memory deficits. In 1941, Walter Freeman, who imported ECT from Europe to
the U.S., wrote:
“The greater the damage, the more likely
the remission of psychotic symptoms. … Maybe it will be shown that a
mentally ill patient can think more clearly and
more constructively with less brain in actual operation” (Freeman, 1941).
The paper was entitled “Brain damaging therapeutics”. Myerson (1942) explained:
“There have to be organic changes or organic disturbances in the physiology
of the brain for the cure to take place. I think the disturbance in
memory is probably an integral part of the recovery process”.
Read,
J., Bentall, R. (2010). The effectiveness of electroconvulsive therapy: A
literature review. Epidemiologia e Psychiatria Sociale, 19, 333-347.
SUMMARY. Aim –
To review the literature on the efficacy of electroconvulsive therapy [ECT],
with a particular focus on depression, its primary target group.
Methods – PsycINFO, Medline, previous reviews
and the eight identified meta-analyses were
searched in an attempt
to identify all studies comparing ECT with simulated-ECT [SECT]. Results –
These placebo controlled studies show minimal support for effectiveness with
either depression or ‘schizophrenia’ during the course of treatment (only for
some patients, on some measures, sometimes perceived only by psychiatrists and
not by other raters), and no evidence, for either diagnostic group, of any
benefits beyond the treatment period. There are no placebo-controlled studies
evaluating the hypothesis that ECT prevents suicide, and no robust evidence
from other kinds of studies to support the hypothesis.
Conclusions – Given the strong evidence (summarised here)
of persistent and, for some, permanent brain dysfunction, primarily evidenced
in the form of retrograde and anterograde amnesia. and the evidence of a slight
but significant increased risk of death, the cost-benefit analysis for ECT is
so poor that its use cannot be scientifically justified.
Declaration of
Interest: Neither author has any
financial conflicts
Ministry of Health
(2004). Use of ECT in New Zealand: A Review of Efficacy, Safety and Regulatory
Controls. Ministry of Health: Wellington, New Zealand.
Sackeim H., et al.
(2007). The cognitive effects of ECT in community settings. Neuropyschophamacology
32, 244-254).
