The Corpus Callosum

Just when you thought there could not possibly be any more to say about
the subject, given the uncertainties inherent in the area, there is yet
another study.  This one is from analysis of a large patient
registry in Finland.  A total of 15,390 patients were included
in the analysis, over a period of 3.4 years.  This study
confirms the finding that antidepressant use does lead to an increase
in suicide attempts.  It also finds that there is a decrease
in actual death from suicide, and a decrease in
overall mortality.

and the Risk of Suicide, Attempted Suicide, and Overall
Mortality in a Nationwide Cohort

Jari Tiihonen, MD, PhD; Jouko Lönnqvist, MD,
Kristian Wahlbeck, MD, PhD; Timo Klaukka, MD, PhD; Antti Tanskanen,
PhLic; Jari Haukka, PhD

Arch Gen Psychiatry. 2006;63:1358-1367.

Background  It is unknown
if antidepressant treatment is associated with either increased or
decreased risk of suicide.

Objective  To estimate the risk of
suicide, attempted suicide, and overall mortality during antidepressant
treatments in a real-life setting with high statistical power.

Design and Setting  A cohort study in
which all subjects without psychosis, hospitalized because of a suicide
attempt from January 1, 1997, to December 31, 2003, in Finland, were
followed up through a nationwide computerized database.

Participants  A total of 15 390 patients
with a mean follow-up of 3.4 years.

Main Outcome Measures  The propensity
score–adjusted relative risks (RRs) during monotherapy with
the most frequently used antidepressants compared with no
antidepressant treatment.

Results  In the entire cohort, fluoxetine
use was associated with the lowest risk (RR, 0.52; 95% confidence
interval [CI], 0.30-0.93), and venlafaxine hydrochloride use with the
highest risk (RR, 1.61; 95% CI, 1.01-2.57), of suicide. A substantially
lower mortality was observed during selective serotonin reuptake
inhibitor use (RR, 0.59; 95% CI, 0.49-0.71; P<.001), and this
was attributable to a decrease in cardiovascular- and
cerebrovascular-related deaths (RR, 0.42; 95% CI, 0.24-0.71; P=.001).
Among subjects who had ever used any antidepressant, the current use of
medication was associated with a markedly increased risk of attempted
suicide (39%, P<.001), but also with a markedly decreased risk
of completed suicide (–32%, P=.002) and mortality
(–49%, P<.001), when compared with no current use of
medication. The results for subjects aged 10 to 19 years were basically
the same as those in the total population, except for an increased risk
of death with paroxetine hydrochloride use (RR, 5.44; 95% CI,
2.15-13.70; P<.001).

Conclusions  Among suicidal subjects who
had ever used antidepressants, the current use of any antidepressant
was associated with a markedly increased risk of attempted suicide and,
at the same time, with a markedly decreased risk of completed suicide
and death. Lower mortality was attributable to a decrease in
cardiovascular- and cerebrovascular-related deaths during selective
serotonin reuptake inhibitor use.

As always, one has to be cautious about drawing general conclusions
from this study.  It is limited to residents of Finland.
 It is limited to patients who had been hospitalized because
of a suicide attempt.  It is limited to patients who did not
have psychosis.  

There are some positives.  The authors appear to have no
conflict of interest.  That is, they are not drug company
shills.  They had a large, comprehensive data set to work

The thing about this study that is at least somewhat reassuring, is
that overall, the use of antidepressants was associated with a decrease
in overall mortality.  Doctors tend to notice things like
that, because it is a bottom-line assessment.  Regardless of
all the nuances and pros and cons and political and sociocultural
issues, if the end result is a reduction in mortality, then you know
you are on the right track.  Or at least not very far off

As for the specifics, it suggests that the old standby, fluoxetine, is
still a good choice.   The deal with venlafaxine and
paroxetine suggests that they should not be first-line drugs, until
further notice.  

As an aside, when patients ask me how to choose an antidepressant, I’ll
sometimes comment that “all other things being equal, if you need a
tiebreaker, the older drugs are preferred over the newer ones.”


  1. #1 PhysioProf
    December 9, 2006

    I have heard it said that the reason antidepressants can increase the incidence of suicide is that in cases of people who are so depressed that they can’t even muster the physical and mental energy to try to kill themselves, it lifts them just enough out of this state that they have the energy to attempt suicide, but not high enough that they no longer wish to die. Is there any evidence that this is actually the case?

  2. #2 Joseph j7uy5
    December 9, 2006

    There is anecdotal evidence about the phenomenon you mention, but not systematic evidence. It is obviously very difficult to find out what motivated people to kill themselves, because after they are successful, they cannot talk anymore.

    It appears that suicide attempts and completed suicide are such different phenomena that it is hard to generalize findings about one class of events to the other. We ask people who attempt suicide why they did it, but what does that tell us about those who actually succeeded in killing themselves? No way to know.

    With that caveat in mind, I can tell you that when people are treaded with antidepressants, not all symptoms improve at the same rate. I can’t recall any citation, but I am fairly sure there are studies showing that psychomotor retardation is one of the symptoms that improves first.

    In fact, it happens sometimes that people will start to look better before they feel better. They look better when they are more lively, have more gestures and facial expression, etc.

    I’ve had patients tell me that it is annoying when, in that early phase, people tell the patient he or she looks better, when they still feel the same. It is kind of alienating when there is that discordance between what the patient experiences inside, and what others tell them they see from the outside.

    But getting back to the point, we can say objectively that energy level tends to improve earlier than other symptoms. What is hard to do, is to prove the link between that and the incidence of suicide or attempts. For what it is worth, mental health professionals do tend to believe they are linked.