SSRIs and the Suicidality Risk: Class Numbers Belie a Deeper Story

On August 11, 2009, the British Medical Journal published an article detailing the results of a study aimed at measuring the association between modern antidepressants (Prozac, Paxil, Zoloft, Celexa, Lexapro, etc.) and increased suicidal thinking and conduct. August 11, 2009 BMJ Article

Although the study results are just now being published in a medical journal, they were first reported to the FDA in November 2006, following the FDA’s collection of clinical trial data from all of the major antidepressant manufacturers. The study was conducted by – and the current articled authored in part by – Marc Stone and Lisa Jones, who are medical officers at the FDA. Nov. 2006 FDA Memo and Attached Report by Stone & Jones

The British Medical Journal article concludes that “[r]isk of suicidality associated with use of antidepressants is strongly age dependent.” The article explains that the increased risk for suicidality and suicidal behaviour among adults under 25 approaches that seen in children and adolescents,” while “the net effect seems to be neutral on suicidal behaviour but possibly protective for suidical ideation in adults aged 25-64.” And the researches posit a “protective” effect for persons aged 65 and older.

What continues to be puzzling about the report is that the investigators seem to go out of their way to compartmentalize risk by splitting the study population into age groups. Why is the cut-off for the bottom group age 25, for instance, instead of age 26? Or age 30? Why is the upper limit for the middle group age 65? How would shifting the age brackets slightly in one direction or the other alter the risk picture? What would the risk look like if there were no age groups?

And why does the study present drug-specific risk figures – which clearly suggest that certain antidepressants pose a greater suicidality risk – and yet reach sweeping, class-wide conclusions about the risk? For instance, Table 5 in the article clearly shows that Celexa (citalopram) and Lexapro (escitalopram) carry a more than two-fold increased risk of “suicidal ideation or worse” compared to placebo (2.11 and 2.44, respectively) for all adults. And these ratios approach statistically significant p-values (0.09 and 0.08, respectively). In other words, it appears that this risk might be real for these two drugs.

Furthermore, it is curious that the authors decided to exclude from the BMJ article a table that appeared in their original report to the FDA: Table 16. That table, which showed figures for all adults for “suicidal preparation or worse,” demonstrated that Paxil (paroxetine) carries a 2.76 increased risk, which was statistically significant (p-value 0.02), and that Lexapro carries a 5.67 increased risk, which approached statistical significance (p-value 0.06). Why is this table missing from the BMJ article?

The most troubling part about the numbers is that they are not readily available to the physicians who prescribe these drugs. Indeed, current antidepressant labeling discloses the increased risk of suicidality for those aged 25 and under but stops short of articulating any association for other age groups. 2009 Lexapro Prescribing Information

On the whole, the article – and the 2006 report that spawned it – smack of a continued effort to minimize, downplay, and contain the increased risk of suicidality that may be posed to all age groups by ingestion of modern antidepressants.