Tuesday, April 12, 2016
The results you want to see.
In recent years, there's been a great deal of controversy surrounding antidepressant medications. In 2007, the FDA issued a black box warning advising against the prescription of selective serotonin repute inhibitors (SSRIs) for treating patients under the age of 25. While this age group encompasses multiple developmental periods, adolescence is particularly important in the context of depression and other psychiatric disorders. Why? As figure 4 from Paus et al., 2008 shows (above) about half of all mood disorders (including depression) emerge during adolescence. While there are still multiple treatment options are available to adolescent patients with depression, as mentioned earlier, one of the main treatment approaches is known to cause depression symptoms to worsen in this population.
While there has been debate about whether SSRIs actually do more harm than good in treating adolescents with depression, one recent meta-analysis not only confirmed increased suicide ideation following SSRI treatment in children and adolescents, but also noted cases of increased aggressive behavior and advocated for close monitoring of all patients being treated with SSRI's - regardless of age. While these findings from the meta-analysis are new, these drugs have been prescribed for multiple decades.
The authors of the meta-analysis points out how the drug company Eli Lilly either misrepresented, or omitted, incidences of suicide ideation and suicide attempts in their summaries of patients who were assigned to receive SSRIs during drug trials. This reminded me of the section of our textbook that dedicated to discussing outliers. Specifically, Motulsky notes, "Even if you try to be fair and objective, your decision about which outliers to remove will probably be influenced by the results you want to see" (p.210). Furthermore, the author warns against occluding outliers if the outlier simply reflects biological variability. While we may not yet know the precise biological mechanism by which SSRIs contribute to worsened depression symptoms and suicide in adolescents, we do know that the adolescent brain undergoes significant changes during this developmental period. For this reason, when you compare the adolescent brain with the adult brain, you are really comparing organs with two completely different biologies.
One of the focuses of the lab I work in is geared towards finding antidepressant alternatives to SSRI's, and testing the short-term and long-term therapeutic potential of administering these drugs during adolescence. I believe that reports such as Sharma et al., 2016 shed light on skewed outcomes from prior drug trials that could be partially explained by excluding certain data points. The prior exclusion of data collected from patients treated with SSRIs during drug trials may play a role in terms why, only in recent years, risks associated with SSRIs have been revealed in adolescent populations and are still viewed as debatable.