Antidepressants’ Black-Box Warning <\/a><\/div>\n
– 10 Years Later<\/a><\/div>\n
by Richard A. Friedman, M.D.<\/div>\n
New England Journal of Medicine<\/font><\/strong> 2014 371:1666-1668.<\/div>\n
[full text on-line<\/a>]<\/div>\n<\/blockquote>\n
The core of this seemingly endless debate about the Black Box Warning revolves around a more fundamental question about the source of medical knowledge – observations made on the collective? or on individual cases? Obviously the answer is some version of both<\/em>, but this debate puts the subtilties of the distinction in bas-relief:<\/div>\n
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- \nCase Reports:<\/font><\/strong> There are ample collections of case reports [SSRI Stories<\/a>, Rx<\/font>isk<\/font><\/a>, etc] that document the syndrome of Akathisia with suicidal and homicidal thoughts and acts. And the most convincing evidence comes from personal encounter. Having seen such cases, I have no question that it is a very real phenomenon, though uncommon. <\/div>\n<\/li>\n
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Data from RTCs [Randomized Clinical Trials]:<\/font><\/strong> Meta-analyses, notably the FDA review by Hamads et al, find a small but significant increase in suicidality in the Clinical Trials of antidepressants in youth. <\/div>\n<\/li>\n- \n
Population Studies:<\/font><\/strong> The majority of authors who oppose or want to revoke the Black Box Warning base their arguments on the collection of population studies that come from a variety of sources. They show that the Black Box Warning did decrease anti-depressant prescription rates particularly in youth. Most of these studies show no real change in the overall rates of suicidal thinking or completed suicide. <\/div>\n<\/li>\n<\/span><\/ul>\n
This debate is further complicated by controversy over the efficacy of antidepressant treatment in depressed children and adolescents. Only two of the SSRIs [Prozac and Lexapro] have been approved by the FDA for the treatment of pediatric depression. And none of the RCTs [including those of these two drugs] have shown anything like a robust response in this age group: <\/p>\n\n
Newer generation antidepressants for depressive disorders in children and adolescents<\/a><\/div>\nCochrane Systematic Reviews<\/font><\/strong><\/div>\nby Sarah E Hetrick, Joanne E McKenzie, Georgina R Cox, Magenta B Simmons, and Sally N Merry<\/div>\n14 NOV 2012<\/div>\n… Based on 14 of the trials [2490 participants in total], there was evidence that those treated with an antidepressant had lower depression severity scores than those on placebo, however, the size of this difference was small. Based on 17 trials [3229 participants in total], there was evidence of an increased risk [64%] of suicide-related outcomes for those on antidepressants compared with those given placebo…<\/p>\n<\/blockquote><\/div>\n
The argument mounted by people who support the Black Box Warning is simple, coming primarily from the case reports: The syndrome does occur and both doctors and patients need to know about it. It’s what the warning says:<\/div>\n![](\"http:\/\/1boringoldman.com\/images\/black-box-1.gif\")
<\/div>\nThe argument coming from the anti-Black-Box set is more complex. They propose that the Black Box Warning itself discourages doctors from prescribing and patients from taking antidepressants, so depressed youth are going untreated. In Friedman’s paper<\/a>, he says:<\/div>\n\n
Nevertheless, given the overall direction of these trends, it is critically important for primary care providers, who see and treat a substantial proportion of depressed patients, to know that the risk posed by untreated depression — in terms of morbidity and mortality — has always been far greater than the very small risk associated with antidepressant treatment.<\/font><\/strong> We need to better educate physicians, to help them understand that although they cannot ignore that small risk, they can safely manage it by carefully monitoring their patients, particularly children and adolescents, during pharmacotherapy.<\/div>\n<\/blockquote>\nThen he concludes:<\/div>\n\n
What should the FDA do in light of these observational data? Given that the agency’s 2007 modification of the black-box warning has not been sufficient to prevent what seems to be a chilling effect on depression treatment — perhaps the mere presence of a warning speaks louder than any clarification it may contain — I believe it’s unlikely that further modification would be helpful. I would therefore argue that the FDA should consider removing the warning entirely…<\/div>\n<\/blockquote>\nThe «chilling effect on depression treatment<\/font><\/strong><\/em>» punch line in this argument is hard for me to take, or for that matter, even follow. The notion that the antidepressant drugs are effective enough in pediatric depression to warrant Dr. Friedman’s «chill<\/font><\/strong><\/em>» is unsupported by anything I can see. And as for «the risk posed by untreated depression»<\/font><\/strong><\/em>, those unmedicated subjects have actually been well studied<\/em> themselves. They’re the Placebo Groups in each of those Clinical Trials.<\/div>\nWell, I wasn’t «chilled<\/font><\/strong><\/em>» by what I recalled of that paper Friedman is talking about, by Lu et al<\/a>, so I went back for another look. I still wasn’t impressed that the Black Box Warning had that big an effect. I noticed that their graphs were drawn on different scales for adolescents, young adults, and adults. So on a lark, I graphically transposed the antidepressant usage onto a single graph with a unified scale, and look what happened…<\/p>\n
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