Ever since the FDA added Black Box warnings to antidepressants in 2004 over concerns the drugs could lead to teenage suicidal thoughts and actions, there has been debate and controversy over the extent to which, if any, the warnings did a different kind of harm. To wit, some experts argued the publicity about side effects may have robbed teens of needed treatment. In particular, studies suggested teen suicides subsequently rose (seehere and here).
Now, a new paper from the National Bureau of Economic Research attempts to measure the purported fallout in a different way. The researchers reviewed data from National Survey on Drug Use and Health from 2001 through 2007, and examined academic and behavioral outcomes in more than 100,000 youngsters between ages 12 and 17. They then designed a study to compare outcomes for those with and without a recent episode of probable depression, which was defined as having sought professional help for depression problems in the previous 12 months.
And what did they find? "In the periods before the FDA warnings, there are no discernable trends in average grades for adolescents with and without probable depression. After the FDA warnings, the average grades dropped abruptly for depressed girls, though not for depressed boys," they write. "...We find that in 2002 and 2003, adolescents with probable depression had grade point averages .14 to .20 points higher than adolescents with depression in the latter half of 2004 and 2005." Put another way, the grade point averages fell roughly from a B to B-.
Adolescents with a recent episode of probable depression were 8.6 percentage points less likely to earn a B or better and 3.5 percentage points less likely to earn a C or better after the FDA advisories in early 2004, they continue. The change was driven by depressed girls, who were 11 percentage points less likely to earn a B or better and 6 percentage points less likely to earn a C or better following the FDA warnings. There appears to be little effect of FDA advisories and the decline in depression treatment on the likelihood of reporting an A average, though. No explanation is given.
Grades were not the only focus. The researchers found "similar patterns" for substance use and delinquency for adolescents with probable depression, relative to other adolescents. For instance, although depressed adolescents are much more likely to binge drink than their peers, the FDA advisories appear to have had little effect on binge drinking. But there was no significant effect of the FDA warnings on attacks on others.
However, among girls, the FDA advisories and decline in the treatment of depression increased the use of illicit drugs by 5.4 percentage points and increased non-medical prescription drug use by 4.3 percentage points, according to the paper. As with academic outcomes, the effects on illegal drug use and non-medical prescription drug use are driven mainly by girls rather than boys, although the effects on cigarette use are similar across gender.
Those were depressed engaged in this sort of experience more often, according to the researecher. About 42 percent of boys and 34 percent of girls with a recent episode of depression reported one or more fights in the past 12 months, compared with 25 percent of boys and 17 percent of girls in the non-depressed group. Stealing and “attacking” with the intent to hurt someone was less common. Less than 10 percent of non-depressed youngsters reported this behavior, while 23 percent of boys and 15 percent of girls in the depressed group had attacked someone in the pevious 12 months.
And substance use was more common among depressed adolescents, with 16 percent of boys and 19 percent of girls reporting binge drinking; , 21 percent of boys and 26 percent of girls reporting smoking cigarettes; 22 percent of boys and 21 percent of girls using an illicit drug; and 8 percent of boys and 9 percent of girls using prescription drugs inappropriately in the previous 30 days.
The upshot? "Among depressed girls, where the effects are concentrated," the authors write, "treatment with antidepressants increases grades by a full point (from a C to a B, for example), reduces the chance of smoking and illicit drug use by 20 to 25 percentage points, and reduces the chance of stealing or fighting by even greater magnitudes (about 30 to 35 percentage points).
"These suggest both large effects of untreated or undertreated depression, as well as an impressive treatment effect of antidepressants in the community during the period leading up to advisories and warnings regarding antidepressants," they conclude. The authors are Susan Busch, an associate professor of public health at Yale University; Ezra Golberstein, an assistant professor at the University of Minnesota School of Public Health, and Ellen Meara, an associate professor at the Dartmouth Institute for Health Policy and Clinical Practice (here is the NBER paper).
Not surprisingly, the paper has already generated some pushback. For instance, Bijan Esfandiari , an attorney with the Baum Hedland law firm, which has filed lawsuits against various drugmakers over antidepressants warnings and disclosure of clinical trial data, such as GlaxoSmithKline and its Paxil pill, argues the NBER paper wrongfully accepts the premise that teen suicides rose as a result of the warnings. Instead, he maintains that suicide rates fell after the FDA warnings were implemented.
On his website, he writes that "the unwarranted conclusions from the underlying studies on which the working paper authors rely have resoundingly been debunked" by other scientists and the FDA, among others (look here). Some of the papers he refers to were co-authored by academics who had extensive financial ties to drugmakers that sell antidepressants. Among them was Charles Nemeroff (see this). "Any suggestion that reduced prescriptions of antidepressants have resulted in countless suicides is simply not supported by the data," he argues.
14 Comments
Do the studies cited above actually attribute "countless suicides" to reduced Rx's, as plaintiff's counsel maintains?
Seems like the classic rhetorical approach of exaggerating the position of the other side, then debunking it. But admittedly I haven't read them.
The researchers make improbable links in their study design. The positive effects of the antidepressants themselves have been extensively debunked in the literature. The results sound like something that NAMI can get behind, however, though they are busy at the moment decrying potentially decreased funding for efforts identifying even younger children who need "mental health attention" (drugs).
Just a technical point on terminology:
Here at the FDA we dont call them "black box warnings" we just call them "boxed warnings"
There is a bit of science which is consistently (or conveniently) overlooked when it comes to teens or children and antidepressants. Whether you are talking about depression or anxiety, children do better with counseling (especially cognitive behavioral counseling) than they do with medications alone. The findings from two separate large NIH funded studies (one for depression and one for anxiety) consistently showed that CBT produced equal or better (and safer) positive results than medication alone. Combining medication with counseling therapy may add to treatment. My conclusion is that any child with depression or anxiety who does not receive counseling is under-treated (and more at risk for suicidal thoughts).
Does anyone know if and how the authors controlled for counseling? I would say that if they didn't their study is not meaningful.
It is also worth noting that anxiety is far more common in children and adolescents than is depression.
Thank goodness for grade inflation. Imagine how bad the grades might be without it.
I, too, haven't seen the studies. But the number of variables would seem overwhelmingly against being able to conclude anything from what I read in Ed's report.
First, we would need to know whether there is actually any difference in rx's. From what I gather, there is not data to that effect.
Second and beyond, there are a zillion intervening variables why students may be struggling--parents unemployed, home foreclosed, need to work more after school to make ends meet, part of increasingly impoverished so-called "middle class," etc. etc. etc.
Unless such dimensions are accounted for, to suggest that all this has something to do with FDA warnings, if that's what is claimed, is more cynical rapacity which ought to provoke our contempt.
Google "Department of Justice" with any of the following: Lexapro, Celexa, Paxil, Zyprexa, Serquel, Respirdal, Geodon Neurontin.....etc.
You tell me who is not doing their home work? And who is cheating at school? And who are the bullies in the playground?
JiM is correct. In biostatistics this is similar to the phenonomenon of Multiple Comparisons, which basiically means that if you repeat the same statistical test often enough with different vartiables there is 1/20 chance (P = 0.05) that one of the results will be statistically significant by random chance alone. This is why, when analyzing multiple comparisons it is important to re-calculate the probabilities or confidence intervals obtained from a statistical test which was repeated multiple times.
I'm guessing that, in answer to my own question, no one, in fact, has said there have been "countless suicides" due to reduced Rx's.
M Helm-Wouldn't be surprised if what you're saying is correct. The problem is that drugs are much cheaper, especially now with patent expirations coming en masse. There are a lot of people on this site who complain about drug companies striking deals to extend patent life, which is understandable. But the other side of the equation is that when these drugs lose their patent, they turn into quick fixes for schools, nursing homes & other financially burdened sectors of the economy. No one seems to mention that, for some reason.
Best thing to remember when reading about a "new study" distributed by NBER is that NOT A SINGLE NBER PAPER IS PEER-REVIEWED. (Only if later published in a journal is it peer-reviewed for that journal, and economics has notoriously weak peer-review standards compared to medicine.)
It's stunning that the media pay attention at all to NBER papers, given that have not been scientifically vetted in a single- or double-blind peer review process.
As to the findings, I don't know whether they're credible or not, but a lot of things were changing when those warnings were added. Unless all of them were controlled for, there may be a spurious association here.
No.
Yes, I would like to suggest that the new FDA warnings on antidepressants are responsible for the "Arab spring" and the range of changes we've seen in North Africa.
It is obvious that all those depressed people in Tunisia, Libya, and Egypt were not getting the treatment they needed and, instead of dealing with their mood disorder, acted out their "dysphoria" by toppling Ghadaffi, Mubarak, et. al..
How tragic!
It's just more "Junk Science" targeted at the adolescent female population..
Thought it was time for this ole gal to chime in!..LOL
Good to see you, Lisa!
The appearance of junk studies is itself depressing but, based on responses here, I believe the "students" are doing well.