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Re: NYTimes:Debate on SSRIs and Suicide risk continues » jrbecker

Posted by Larry Hoover on August 7, 2003, at 11:43:31

In reply to NYTimes:Debate on SSRIs and Suicide risk continues, posted by jrbecker on August 7, 2003, at 9:47:43

> looks like the mass media is going to grab a hold on this one again due to the latest paxil concerns in children
>
> http://www.nytimes.com/2003/08/07/health/07DEPR.html?hp

I'd like to add some context to this debate. What's being identified in this article, and similar pieces, is a short-term risk of suicidality which occurs early in treatment. That risk is not unique to Paxil, nor to SSRIs as a class. It has long been recognized as a risk of antidepressant therapy, in general.

I'm going to post a couple abstracts, with my comments.

J Affect Disord. 1996 Nov 4;41(1):1-8.

Epidemiological data suggest antidepressants reduce suicide risk among depressives.

Isacsson G, Bergman U, Rich CL.

Department of Clinical Neuroscience and Family Medicine, Division of Psychiatry, Karolinska Institute, Huddinge University Hospital, Sweden. goran.isacsson.@cnsf.ki.se

In spite of the availability of antidepressant medication for several decades, it has not been shown that such medication lowers the risk for suicide in depressed patients. This report explores this apparent paradox by means of pharmacoepidemiological methods. Data on the prevalence of depression in the population and among suicides as well as data on the prevalence of antidepressant medication in depressed suicides were obtained from a review of the literature. Data on the prevalence of antidepressant medication in the population in 1990-1991 were obtained from the statistics of the Swedish National Corporation of Pharmacies. It was found that only one in five depressed individuals with major depression were treated with antidepressants in Sweden. The calculated risk for suicide among depressed patients who were treated with antidepressants was 141 per 100,000 person years and, among the untreated, 259 per 100,000 person years (i.e., 1.8 times higher among the untreated). This supports the hypothesis that antidepressant medication decreases the risk for suicide in depressed patients. The reason this has not been obvious in the general suicide statistics seems to be that so few depressed people are treated with antidepressants. Effective suicide prevention strategies should include intensive efforts to recognize and treat more depressed people.

Comment: Note the confounding influence of the generally low rate of treatment of depression, which serves to obscure (by dilution) the benefit accruing from pharmacological treatment. Moreover, as this study does not distinguish in any way the group of suicides arising *from* treatment (they are included in the group statistic), there is a net benefit from pharmacological treatment, in the context of suicide.


Pharmacoepidemiol Drug Saf. 2001 Oct-Nov;10(6):525-30.

Antidepressant medication and suicide in Sweden.

Carlsten A, Waern M, Ekedahl A, Ranstam J.

Department of Social Medicine, University of Goteborg, Sweden. anders.carlsten@telia.com

OBJECTIVE: To explore a possible temporal association between changes in antidepressant sales and suicide rates in different age groups. METHODS: A time series analysis using a two-slope model to compare suicide rates in Sweden before and after introduction of the selective serotonin reuptake inhibitors, SSRIs. RESULTS: Antidepressant sales increased between 1977-1979 and 1995-1997 in men from 4.2 defined daily doses per 1000 inhabitants and day (DDD/t.i.d) to 21.8 and in women from 8.8 to 42.4. Antidepressant sales were twice as high in the elderly as in the 25-44-year-olds and eight times that in the 15-24-year-olds. During the same time period suicide rates decreased in men from 48.2 to 33.3 per 10,000 inhabitants/year and in women from 20.3 to 13.4. There was significant change in the slope in suicide rates after the introduction of the SSRI, for both men and women, which corresponds to approximately 348 fewer suicides during 1990-1997. Half of these 'saved lives' occurred among young adults. CONCLUSION: We demonstrate a statistically significant change in slope in suicide rates in men and women that coincided with the introduction of the SSRI antidepressants in Sweden. This change preceded the exponential increase in antidepressant sales.

Comment: A temporal association is literally coincidence. That said, coincidence does not mean "no relationship". There is a significant relationship between the introduction of SSRI medication and the change in the rate of suicide. That significant relationship is revealed by what they describe as a "significant change in slope" of the rate of suicide plot. This, from a statistical perspective, requires the introduction or removal of an independent variable, as the dependent variable plots to a different regression line (i.e. change in slope). The only change they identify is the introduction of SSRI medication (a new independent variable). So, even if SSRIs do lead to a short-term enhancement in the risk of suicide, the long-term risk (which embeds the short-term increase within it) is reduced.

What I find to be compelling about the latter study is that the subjects are the inhabitants of an entire nation. Unlike clinical trials, in which subjects do not have comorbid diseases, and are selected for disease severity and other things, the population under study (everybody in Sweden) includes substance abusers, people with comorbid conditions, people prescribed the meds off-label, people of all ages, those who stopped taking the meds or who didn't take it as prescribed, and so on. The entire gamut of human experience. All they're saying is, that at the same time SSRIs were added to the mix, suicide rates declined significantly.

What I wish to emphasize is that people need adequate supervision when initiating pharmacological treatment for depression. To blame the drugs is a little bit short-sighted. The issue is how the patients are managed, under care.

Lar

 

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poster:Larry Hoover thread:248910
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