The FDA’s Antidepressant Warning Didn’t Really “Backfire”

By Neuroskeptic | June 24, 2014 5:31 am

We read this week that

‘Black Box’ Warning on Antidepressants Raised Suicide Attempts
A so-called “black box” warning on antidepressants that the medications increase the risk of suicidal thinking and behavior in kids may have had a horrible side-effect. New research finds the warning backfired, causing an increase in suicide attempts by teens and young adults.

The research in question is this paper in the British Medical Journal from Harvard researchers Christine Lu and colleagues.

The move that supposedly backfired was the US Food and Drug Administration (FDA)’s 2004 decision to issue an official ‘black box’ warning concerning the fact that antidepressants may cause suicidal thoughts and behaviors in children and teens.

Lu et al say that this warning was followed by decreased antidepressant use in this age group but, ironically, the rate of suicide attempts rose.

And while the authors never outright state that the FDA’s warning caused the extra suicide attempts, they strongly imply that, using phrases such as

It is disturbing that after the health advisories, warnings, and media reports […] we found substantial reductions in antidepressant treatment and simultaneous, small but meaningful increases in suicide attempts.

Are they right to be disturbed? By my reading – no. Their data just don’t support a causal effect. The reason why is quite simple:


This montage shows, for three age groups, the timeseries for three variables: antidepressant use, (a proxy measure for) suicide attempts, and actual suicides. The grey band on each graph shows 2004, the year of the FDA warning. Data are anonymized records from the MHRN.

From the graphs, we see that in adolescents, the warning was followed by a sharp (though not enormous) drop in antidepressant use. This drop was accompanied by a rise in suicide attempts. However (red box) an even larger rise was seen in young adults (age 18-29) over the exact same time period, yet antidepressant use did not fall in this group. Use stopped rising at this point, but it didn’t fall.

This seems clear evidence against a causal link between antidepressants and suicide attempts. The rise in suicide attempts in young adults can’t have been caused by a fall in antidepressant use, because there was no fall in that age group. It must have been caused by another factor. Given which, it would be parsimonious to assume that this unknown factor was responsible for the rise in suicide attempts in teenagers as well. (There were no effects on actual suicides in any age category.)

Remarkably, however, Lu et al. come to a very different conclusion, saying (my emphasis) that “we found substantial reductions in antidepressant use […] among adolescents and young adults“.

What Lu et al. mean is that antidepressant use in young adults ‘fell’ relative to what it ‘would’ have been, sans FDA warning, i.e. assuming that the previous increasing trend had continued (shown as the red dashed line on the graph). But that’s silly. By that logic, when a child becomes an adult and stops growing, their height ‘decreases’! Extrapolated red dashed lines aside, there was no decrease.

So that’s that. But I must point out that many of the critics of this paper have also been silly. Check out the BMJ Rapid Responses‘. There’s some good comments there, but they are accompanied by tenuous speculation and irrelevant pontificating about antidepressants.

The key point about the non-existent ‘decline’ in antidepressant use in young adults was made by Dr Mark Olfson and later by Dr Bernard Carroll. But these sensible voices were drowned out by the sound of axes being ground and dead horses beaten.

Finally, while these results don’t establish that decreasing antidepressant use increased suicides, they equally provide no evidence that it decreased them. Rather, Lu et al.’s study joins the many others that have found no correlations between antidepressant use and suicide rates, in either direction, at a population level.

ResearchBlogging.orgLu CY, Zhang F, Lakoma MD, Madden JM, Rusinak D, Penfold RB, Simon G, Ahmedani BK, Clarke G, Hunkeler EM, Waitzfelder B, Owen-Smith A, Raebel MA, Rossom R, Coleman KJ, Copeland LA, & Soumerai SB (2014). Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study. BMJ (Clinical research ed.), 348 PMID: 24942789

  • BrightUmbra

    “Correlation is not causation” – is one of the HARDEST things to explain to lay people. It goes so far against our intuitions – thing A happened, then thing B happened, so thing A MUST have caused thing B! Getting people to understand why that isn’t always so is one of the biggest challenges I’ve faced in my, um, impromptu debates with people.

    There’s got to be a good way to teach this, without simply leaning on example.

  • Amtram

    Lies, damn lies, and statistics. I knew this sounded too made-for-TV.

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  • Lily Dryburgh-Smith

    Whilst parsimonious to assume the factor causing the increase in suicides is the same in both groups is the same, surely it is more plausible that the increase is explained by an increased proportion of more seriously depressed individuals in the teenage treatment group than before the warning?

    • Neuroskeptic

      Ah – I think I wasn’t very clear. The rates of suicide attempts are rates in the whole population, not within the treated group only.

  • Praz Nina

    I’m not sure why they claim there is a correlational link between the drop in antidepressant use and the increased proportion of suicide attempts. There are two more plausible explanations:

    1. Placebo (then it needs to be explored why the adult group is not so susceptible, maybe they don’t even know what the black box mean or they have been using ADs for so long and haven’t made suicidal attempts, so why would they now?)

    2. People become afraid and only severe cases (with a priori higher chance of suicide attempt) stay on/take medication.

    To determine which one of those is more probable, absolute numbers would be needed as well, not just percentages.

  • Enopoletus Harding

    Might the FDA warning have inspired young people to attempt suicide?

  • Matt

    1BOM has been extensively covering this over the past week or so –

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  • Evie S.

    Washington Post used these two graphs to bring the black box warning into question, ignoring something that’s easier to see when you draw a vertical line a few years after 2004. It appears that self-poisonings with psychotropic drugs (a lousy proxy for suicide due to lack of psychotropic drugs, by the way), were stable until antidepressant prescriptions were on the rise again.

    Self-poisoning by the young might be positively related to prescriptions for antidepressants for parents, by the way.

  • Flat 5

    Christine Lu is the archetype of the blinkered scientist, doing research shuttered away in a lab, while remaining utterly blind to the influence of socio-economic events. As if the only determinant of the public mood was the amount of pharmaceutical product coursing through the national bloodstream!! Psychotropic drug overdoses as a measure of suicide attempts?? At the nadir of the Bush Disaster and the height of the “rave drug” epidemic??? These kids weren’t trying to kill themselves. They were partying!! (in a dangerous way). Christine Lu is just another Pharma Pawn, bucking for a $3 million per year Pharma Sinecure…like Julie Gerberding got…



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About Neuroskeptic

Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.


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