Lack of Perspective in New Suicidality Warning for Antidepressants

Editor, Primary Psychiatry and Psychiatry Weekly, Professor of Psychiatry, New York University School of Medicine

When an advisory panel recommended in mid-December that all antidepressants should have their labeling amended to reflect findings of an increased risk of suicide linked to antidepressant use, virtually every newspaper and news program carried the story. This has long been a controversial issue, with debate about the risk of drug-induced suicidality playing out in public venues since at least the late 1980s.

The most recent label change is an extension of the product information warnings about antidepressant-associated suicide risk to include patients between the ages of 18 and 25, and is based on an analysis of antidepressant drug trials finding that adults under 25 administered the drugs were more than twice as likely as those on placebos to attempt, think about, or prepare for suicide.

Because the news reports have sensationalized the findings of the analysis, it might be worth putting some perspective on what was and was not found:

• In the studied population, actual suicidal behavior was extremely rare. In part, this is due to the fact that patients with suicidal ideation are routinely excluded from antidepressant trials. Consequently, none of the studies used in the analysis were able to determine the degree to which being on medication reduced suicidality. The trials were not designed to evaluate suicide risk.
  
  
• None of the patients taking antidepressants killed themselves
  
  
• The antidepressant drugs appeared to reduce the risk of suicidal behavior significantly in people 65 and over. Among those in the 25 to 65 age group, the antidepressants did not differ from placebo in causing suicidality
  
  
• The 2004 warning for children and adolescents made more sense, since the studies failed to demonstrate that antidepressants were effective in that population. The risk-benefit ratio was weighted more toward the risk. In the current analysis, while there was a clear increase in “suicidality,” the population aged 18 to 25 has been shown to respond to antidepressants in clinical trials.

While it cannot be disputed that there is a statistically increased risk of suicidal ideation and gestures among some subjects treated with antidepressants in clinical trials, the risk is very small.

Clearly, any potentially fatal treatment-emergent event needs to be made known to clinicians, disclosed to patients and their families, and monitored by both clinicians and patient families; unfortunately, what is lost in the news accounts of the FDA action is that depression is by far the most common cause of suicide. There is thus reason to believe that many more patients are prevented from committing suicide as a result of taking medication than become suicidal from the treatment. By narrowly focusing on the statistical aspects of risk in clinical trials, and by not providing some narrative that puts the subject of suicide into the broader clinical context, the latest warning could paradoxically increase the number of suicides, as patients and clinicians perceive treatment to be more dangerous than the disease itself.

Disclosure: Dr. Sussman has received honoraria from AstraZeneca, Bristol-Myers Squibb, and GlaxoSmithKline.