- a madness to our method…
- are you listening?…
- another campaign?…
- a madness to our method – a new introduction…
Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental studyby Christine Y Lu, Fang Zhang , Matthew D Lakoma analyst, Jeanne M Madden, Donna Rusinak, Robert B Penfold, Gregory Simon, Brian K Ahmedani, Gregory Clarke, Enid M Hunkeler, Beth Waitzfelder, Ashli Owen-Smith, Marsha A Raebel, Rebecca Rossom, Karen J Coleman, Laurel A Copeland, Stephen B SoumeraiBritish Medical Journal. 2014 348:g3596.
Objective To investigate if the widely publicized warnings in 2003 from the US Food and Drug Administration about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed suicides among young people.Design Quasi-experimental study assessing changes in outcomes after the warnings, controlling for pre-existing trends.Setting Automated healthcare claims data [2000-2010] derived from the virtual data warehouse of 11 health plans in the US Mental Health Research Network.Participants Study cohorts included adolescents [around 1.1 million], young adults [around 1.4 million], and adults [around 5 million].Main outcome measures Rates of antidepressant dispensings, psychotropic drug poisonings [a validated proxy for suicide attempts], and completed suicides.Results Trends in antidepressant use and poisonings changed abruptly after the warnings. In the second year after the warnings, relative changes in antidepressant use were −31.0% [95% confidence interval −33.0% to −29.0%] among adolescents, −24.3% [−25.4% to −23.2%] among young adults, and −14.5% [−16.0% to −12.9%] among adults. These reflected absolute reductions of 696, 1216, and 1621 dispensings per 100 000 people among adolescents, young adults, and adults, respectively. Simultaneously, there were significant, relative increases in psychotropic drug poisonings in adolescents [21.7%, 95% confidence interval 4.9% to 38.5%] and young adults [33.7%, 26.9% to 40.4%] but not among adults [5.2%, −6.5% to 16.9%]. These reflected absolute increases of 2 and 4 poisonings per 100 000 people among adolescents and young adults, respectively [approximately 77 additional poisonings in our cohort of 2.5 million young people]. Completed suicides did not change for any age group.Conclusions Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts among young people. It is essential to monitor and reduce possible unintended consequences of FDA warnings and media reporting.
Study cohorts and outcome measures…Because previous studies showed that rates of depression diagnosis changed after the warnings and that outpatient claims are often incomplete for mental health conditions such as depression, to avoid introducing selection bias, we did not limit our cohorts to those with a coded diagnosis of depression.
…To examine changes in suicide attempts after the warnings, we used the same denominator population as defined previously. While encounters for suicide attempts can be identified in administrative databases using external cause of injury codes [E-codes], they are known to be incompletely captured in commercial plan databases. Our preliminary analysis found that E-code completeness varied across study sites, treatment settings, and years. Therefore, instead of deliberate self harm E-codes, we used poisoning by psychotropic agents [international classification of diseases, ninth revision, clinical modification [ICD-9] code 969], a more reliable proxy for population level suicide attempts. Poisoning by drugs or toxic substances is the most common method of suicide attempt leading to hospital admission and emergency room treatments. 35 36 Non-fatal poisoning by psychotropic drugs [predominantly tranquilizers] has a positive predictive value of 79.7% for suicide attempts [sensitivity was 38.3% and specificity was 99.3%], outperforming other types of injuries or poisonings..
Decline in treatment of pediatric depression after FDA advisory on risk of suicidality with SSRIs.
by Libby AM, Brent DA, Morrato EH, Orton HD, Allen R, Valuck RJ.
American Journal of Psychiatry. 2007 164:884-891.
[full text online]
Persisting decline in depression treatment after FDA warnings.
Libby AM, Orton HD, Valuck RJ.
Archives of General Psychiatry. 2009 66:633-639.
[full text online]
At face value, the whole premise for the study is flawed. The SSRIs have only been shown to be effective in pediatric depression in Lilly’s earliest studies of Prozac, and in spite of their creative publications, the remainder have been ineffective. So, the idea that the SSRIs are even treatment for adolescent depression is in question, much less much a suicide attempt preventative. There is no direct linkage between the decrease in prescribing and their outcome parameter to validate the association implied. And the thing they actually measured is in itself a proxy for another proxy, based on the evidence from the most compromised of sources. My own takeaway from this article is that, once again, this was an attempt to answer a question using a huge dataset from a commercial administrative data, and it wasn’t up to the task. Having access to that much data is certainly tempting, but the absence of reliable E-coding doomed the study before it ever got off the ground. The errors intrinsic in any proxy, much less a second generation proxy, will probably never make them useful in answering subtle scientific questions.
There is a much larger question in this story, a question that has been present from the start – case studies versus population data. If you’ve seen Akathisia and suicidality in cases of adolescents put on SSRIs, and if you know of several completed suicides that you’re convinced were medication induced, how are you to look at a study like this even if you believe it? This line of thinking presumes that the only thing one can do for a depressed teen is give them SSRIs, which has never been true. A blog is no place to launch into all the things one might do besides give a questionable symptomatic medication, how to actually approach a depressed teen. But even common sense tells us that there are a wide range of answers to that question that don’t only rely on medication. And if, after careful consideration, you decide to try an antidepressant, knowing that this kind of reaction can occur in some cases would certainly heavily inform how you would closely follow such a case.
… it is disturbing that after the health advisories, warnings, and media reports about the relation between antidepressant use and suicidality in young people, we found substantial reductions in antidepressant treatment and simultaneous, small but meaningful increases in suicide attempts. It is essential to monitor and reduce possible unintended effects of FDA warnings and media reporting.