Monday, June 07, 2004

More Facts About Antidepressants and Suicide

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 CC posts: 1  2  3  4  5  6  7  8  9)

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 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:

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:

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:

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).

[...] 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) (Figure 1). Furthermore, as detailed in Figure 2, 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:

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 corellations 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. 

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.

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