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The FDA's Antidepressant Safety Warnings: 
a Balanced Summary, September 2007


A recent editorial in the American Journal of Psychiatry, one of the most prominent psychiatric journals in the world, presented a very careful and thoughtful summary of the issues regarding suicidal thinking and children and adolescents for whom an antidepressant is prescribed.  Here is a link to the editorial by Dr. Leckman, but if you'd prefer to read my attempt at a summary in plain English, proceed. If you would like to see a reference for any of the assertions below, see the original article.


Since the 1990s, antidepressant use in children and adolescents has been going up steadily and dramatically -- until the Food and Drug Administration (FDA) warned against possible increases in suicidal thinking and action in some children given these medications.

Since that warning, many mood experts have wondered whether this Warning might actually do more harm than good. If antidepressants really do work, then they may treat depression in people who could otherwise go on to commit suicide because of that illness.  While the evidence for these medications and ability to treat depression in children and adolescents is not as good as it is in adults, there is still good reason to think that they do indeed effectively treat depression in many individuals. Therefore a sharp reduction in the use of these medications in young people whose depression might otherwise have responded quickly to antidepressant treatment might actually lead to an increase in suicides.

Unfortunately, some recent evidence suggests that this potential increase in suicide is actually happening. Dr. Leckman points out carefully some of the flaws in this research, but the result is still worrisome and worth continued consideration and study. Certainly no one would want to see the suicide rate increase as a result of FDA regulation.

In children less than age 12, balancing the risks of medications and potential benefits may be particularly tricky. In that age group, available research suggests that the benefit of antidepressants is only slightly greater than that of a placebo. Overall, Dr. Leckman suggests careful discussions with parents comparing the potential benefit of non-drug treatment. He is not suggesting that antidepressants shouldn't be used, only that the medication approach be carefully thought through -- including the potential risks.

These risks might actually go beyond a moderate increase in suicidal thinking in some of these young children (roughly one child in 50*; this is higher than in adolescents where the rate is harder to characterize but is almost certainly quite a bit lower). Dr. Leckman notes that we know remarkably little about the long-term impact of giving children the antidepressants during a time in which their brains are very rapidly developing. The research we have on this issue is largely from studies of developing mice and rats. In those animals, some very concerning long-term brain changes have been seen when when these young mammals were exposed to antidepressants. On the other hand, because of the way that antidepressants work, it is possible that they lead to brain changes which leave the child better off in the long run (for details on the mechanisms of antidepressants, see my summary of the brain chemistry of depression,  particularly mini-Chapter 6). This remains completely unknown and definitely under-researched.

Nevertheless, the main point of the editorial by Dr. Leckman is that our concerns about safety, including such long-term issues as these, must be carefully balanced against the potential benefits which antidepressants can provide to some individuals. There is almost certainly a middle ground between causing harm by increasing suicidal thinking in some, versus causing harm -- potentially quite significant harm -- by increasing actual suicide rates, if this is indeed resulting from the reduction in antidepressant use in young people. With only a bit more research we may be able to identify those who will benefit, and those who might actually worsen. Some markers for this have already been tentatively identified.

 

*this number is based on interpretation of the overall picture the FDA data suggest in terms of increased risk -- provided by my Child and Adolescent Psychiatry colleague, Dr. Rick Bingham, who reviewed this summary, improving it.  Dr. Bingham is a participant in the research team described by Dr. Leckman, the Child and Adolescent Psychiatry Trials Network (CAPTN).