The Corpus Callosum

Being on vacation over the following two weeks, I’ve scheduled publication of some old posts. The formatting might be a little funny, but I can’t really check that ahead of time. The preview function in MT is not perfect. This one is from June, 2004….

From the newsletter, Psychiatric Times, here is a summary of recent
findings from analysis of data pertaining to the association between
antidepressant use and the incidence of suicide.  I wrote a
flurry
of articles on this subject back in April.  (previous title="Corpus Callosum">CC posts: href="http://corpus-callosum.blogspot.com/2004_03_01_corpus-callosum_archive.html#108079558149980607">1 
href="http://corpus-callosum.blogspot.com/2004_03_01_corpus-callosum_archive.html#108070429064327921">2 
href="http://corpus-callosum.blogspot.com/2004_03_01_corpus-callosum_archive.html#108049844246815314">3 
href="http://corpus-callosum.blogspot.com/2004_03_01_corpus-callosum_archive.html#108043594436480395">4 
href="http://corpus-callosum.blogspot.com/2004_04_01_corpus-callosum_archive.html#108168685298661651">5 
href="http://corpus-callosum.blogspot.com/2004_04_01_corpus-callosum_archive.html#108182769925734237">6 
href="http://corpus-callosum.blogspot.com/2004_04_01_corpus-callosum_archive.html#108191715850665798">7 
href="http://corpus-callosum.blogspot.com/2004_04_01_corpus-callosum_archive.html#108252076120747627">8 
href="http://corpus-callosum.blogspot.com/2004_04_01_corpus-callosum_archive.html#108278477653702456">9)

href="http://www.waypath.com/multibuzz?qs=antidepressant&qs2=suicide&qs3=medication"> src="http://img36.photobucket.com/albums/v108/jyaroch/antidep-suicide-multibuzz.jpg"
title="" alt=""
style="border: 2px solid ; width: 275px; height: 229px;"
align="left">Now,
however, the interest in the topic has waned; people just aren’t
talking about it so much any more.  Despite the fickle nature
of
the sensational-news-consuming public, the scientific community has
retained an interest in the topic. 

Yes, there was an href="http://www.nytimes.com/2004/06/02/health/02DEPR.html?ex=1401508800&en=955e76acdca97d65&ei=5007&partner=USERLAND">article 
in the NYT last week, regarding a study that showed a positive effect
using fluoxetine to treat depressed adolescents.  This article
did
not attract much attention, which, in fact, was appropriate. 
Few
few individual studies deserve front-page coverage in a major
newspaper.  Although the results of the study were
encouraging,
any such study must be viewed in a wider context in order to be
interpreted properly.

Because of the need for a wider context, it was with interest that I
read the recent article in the Psychiatric Times.  The article
reviews the findings of five population-based studies of the
association between antidepressant prescribing and suicide
rates. 

The entire report is fairly short, so it would be almost as easy to ask
readers to just go read the entire thing, as opposed to providing
excerpts here.  However, the article is rather technical,
enough
so that I imagine it would take a sustained effort of will to plow
through it. 


This is one of those articles that starts out by reviewing studies that
reported negative findings, then goes into the ones that show positive
findings, then shows why we should believe the positive findings and
not the negative ones.  Therefore, persons who have already
made
up their minds should not bother reading it.  If you have
decided
already what you believe, this article will not change your
mind. 
If, on the other hand, you are willing to be open-minded about it, you
may find it sways you one way or the other.

Is
Antidepressant Prescribing Associated With Suicide Rates?

by Philip B. Mitchell, M.D., MB, FRCPsych

Psychiatric Times 
May 2004  Vol. XXI  Issue 6

First, the negative findings:

style="color: rgb(153, 0, 0);">In
2003, the eminent European mood disorder researcher Herman van Praag
lamented what he has termed the “stubborn behaviour” of the failure of
antidepressants to reduce suicide rates, arguing that the majority of
evidence does not support any reduction in such outcomes related to the
increased volume of prescribing.
Van Praag highlighted two major issues. First, there have been few
countries reporting sustained reductions in suicide rates, despite the
substantial increase in antidepressant prescribing. Second, randomized,
controlled trials of antidepressants have failed to demonstrate any
effect on suicide. In a most telling report, Khan et al. (2003)
analyzed U.S. Food and Drug Administration summary reports of
controlled clinical trials for nine recently marketed antidepressants.
Similar suicide rates were seen in those randomly assigned to each
SSRI, comparator antidepressant or placebo, failing to provide any
evidence of a suicide-reducing effect of antidepressants.

Next, the limitations of the negative findings:

style="color: rgb(153, 0, 0);">There
are, however, limitations as to how much one can infer from such
trials. Suicide is a rare event, and even in the FDA trials, which
comprised over 48,000 patients with depression, only 77 committed
suicide, making comparisons between treatment groups difficult.
Moreover, such trials exclude entry to those with prior significant
suicidal risk.

Next, the positive findings:

style="color: rgb(153, 0, 0);">Despite
such negative findings, a potential beneficial effect of
antidepressants on suicide rates has become apparent in a recent series
of national population-based reports. The first studies came from
countries that had observed overall reductions in their suicide rates.
Isacsson (2000) and Carlsten et al. (2001) both investigated the
Swedish experience, where there had been a gradual reduction in suicide
rates over the period from 1977 to 1997. They found that the decline in
suicides accelerated after 1990 when the SSRIs were introduced. The
rate of suicides in the 1990s was significantly inversely related to
the rate of antidepressant prescribing in most age and gender groups.
Similarly, in Hungary, rates of suicide declined in parallel with a
rapid growth of antidepressant usage, despite steep increases in
unemployment and per capita alcohol consumption (Rihmer, 2001, as cited
in Hall et al., 2003). The same phenomenon was, however, not observed
in all European countries, with no such association being seen in Italy
(Barbui et al., 1999).

Next, the author’s own findings, which, in their view, indicate that
the positive findings are the ones we should pay attention to:

We
examined the
association between changes in antidepressant prescribing in Australia
for the period 1991 to 2000 (Hall et al., 2003).

One
of the
complexities that faced us, however, was that the total suicide rate
for Australian men and women did not change between 1991 and 2000,
because marked decreases in suicide rates in older men and women were
offset by increases in younger adults, especially young men. A similar
phenomenon has been observed in the United Kingdom, where suicide rates
doubled in males younger than 45 between 1950 and 1998, but rates
declined in older males and females of all ages (Gunnell et al., 2003).
Because of this phenomenon, we analyzed differences in suicide trends
between men and women in different age groups to assess whether age and
gender rates in suicide were related to differences between these
groups in exposure to antidepressant medication (Hall et al., 2003).

style="color: rgb(153, 0, 0);">[...]
We found strong evidence of a beneficial impact of antidepressant
prescribing on suicide rates. Among both men and women, the largest
declines in suicide occurred in the age groups with the highest
exposure to antidepressants across the study period (males, r=-0.91;
females, r=-0.76; both significant) ( href="http://www.psychiatrictimes.com/p040553b.gif"
style="color: rgb(153, 0, 0);">Figure 1 style="color: rgb(153, 0, 0);">). Furthermore, as detailed
in href="http://www.psychiatrictimes.com/p040553c.gif"
style="color: rgb(153, 0, 0);">Figure 2 style="color: rgb(153, 0, 0);">, there was also a
significant inverse
correlation between change in the defined daily dose/1,000 for women
(r=-0.74), with a trend toward significance for males (r=-0.62).

Then, more supporting evidence:

style="color: rgb(153, 0, 0);">The
validity of our findings has been supported by two other studies
published in 2003. In the United States, Olfson et al. (2003) evaluated
the relationship between geographical regional changes in
antidepressant prescribing and suicide in adolescents from 1990 to
2000. A significant negative relationship (after adjusting for
potential confounds such as gender, age, income and race) was found
between regional change in antidepressant medication treatment and
suicide during the study period. They calculated that a 1% increase in
adolescent use of antidepressants was associated with a decrease of
0.23 suicides per 100,000 adolescents per year. The clearest benefits
were found in males, youths aged 15 to 19 and those with lower family
incomes. In the United Kingdom, Gunnell et al. (2003), examining the
period 1950 to 1998, found that the dramatic reductions in suicide
rates in older people were associated with increases in gross domestic
product, the size of the female work force, marriage and the increased
prescribing of antidepressants. This report highlighted that the
population trends in suicide appeared to be associated with a range of
social and health-related factors, with antidepressants comprising one
of the latter.

The author is careful to point out that such correlations do not
establish causation.  They do, however, argue against the
proposition that antidepressant medication is more likely to cause
suicidal behavior than it is to prevent it. 

style="color: rgb(153, 0, 0);">It
is therefore apparent from these studies of five different national
data sets that the recent phenomenon of a substantial increase in the
recognition of depression and greater rates of treatment with
antidepressant medications and psychosocial interventions appears to be
one of the significant contributants to reduced suicide rates in either
total populations, older people or adolescents.

Note that the studies cited by the author are studies of adult
populations.  The recent controversy had more to do with the
risks
of using antidepressant medication in children and
adolescents. 
It looks as though we will have to wait for more definitive information
on that issue.