by Richard A. Friedman, M.D.New England Journal of Medicine 2014 371:1666-1668.
Case Reports: There are ample collections of case reports [SSRI Stories, Rxisk, 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.
Data from RTCs [Randomized Clinical Trials]: 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.
Population Studies: 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.
Cochrane Systematic Reviewsby Sarah E Hetrick, Joanne E McKenzie, Georgina R Cox, Magenta B Simmons, and Sally N Merry14 NOV 2012
… 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…
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. 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.
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…
Well, I wasn’t «chilled» by what I recalled of that paper Friedman is talking about, by Lu et al, 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…
compared to this [a bit of presentation
bias trickery at work in my humble opinion].
The dip in prescriptions for adolescents was not so impressive after all! And as I look at those changes, they’re exactly what I would predict [and want] from the Warning. In all three cases [adolescent, young adult, and adult] it’s not so much that prescription rates even fell, they stopped rising [recall that it’s a percentage scale]. That’s expected, rational, careful – good for them. So back to the thread, I’m really not «chilled» now.
This is my biggest pet peeve with the KOL set. They talk as if a diagnosis of depression means the patient should be on antidepressants. Where did that ever come from? That’s not even true for adults – and it’s absolutely not true for adolescents. These drugs are just not that powerful. And, by the way, they’re still prescribing a whole lot of antidepressants for kids. So Dr. Friedman’s [and other anti-Black-Box-Ninjas’] argument that we need to get rid of the Warning so that Primary Care Doctors won’t be afraid to give these deprived teens antidepressants is unsupportable and totally irrational from any direction I know. Shame on him for even making the suggestion.
by Marc B. Stone, M.D.New England Journal of Medicine 2014 371:1668-1671.