Antidepressants and the Risk of Suicide, Attempted Suicide, and Overall Mortality in a Nationwide Cohort
Jari Tiihonen, MD, PhD; Jouko Lönnqvist, MD, PhD; 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 with.
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 track.
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."
Comments
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?
Posted by: PhysioProf | December 9, 2006 12:11 PM
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.
Posted by: Joseph j7uy5 | December 9, 2006 1:26 PM