1 Boring Old Man

Antidepressant Study Stirs Controversy
Medscape Medical News > Psychiatry
by Fran Lowry
Oct 22, 2012

A recent meta-analysis concluding that 2 antidepressants neither increased nor decreased suicidal thoughts and behavior in children is flawed, Harvard researchers say. However, the authors of the study stand by their article and its conclusion.  The study, led by Robert Gibbons, PhD, of the University of Chicago, in Illinois, was published in the Archives of General Psychiatry and reported by Medscape Medical News. In a letter to the news editor of Medscape Psychiatry, Matthew J. Miller, MD, MPH, from the Harvard School of Public Health, in Boston, Massachusetts, asserts that the study’s conclusion was "misleading."

Far from indicating that the antidepressant-suicide link in youth is absent, the data continue to show what the US Food and Drug Administration [FDA] data show, a 2-fold increase in suicidal thoughts and ideation among children treated with fluoxetine, Dr. Miller writes. He and colleagues Tyler VanderWeele, PhD, and Sonja Swanson also wrote a letter to the editor of the Archives of General Psychiatry outlining their concerns about the investigators’ interpretation of the antidepressant data. The letter was published as a Comment.

"Gibbons’ study of highly selected placebo-controlled randomized studies of antidepressants [n = 9,185] is framed as a counterpoint to and advance over the much larger meta-analyses conducted by the FDA [n = 99,839] that found a 2-fold increased risk of suicidal thoughts and behaviors among children and young adults randomized to antidepressants, and a decreased risk in older adults," Dr. Miller notes.

But in reanalyzing these data, Dr. Gibbons and colleagues use mediation analyses, which are subject to bias, the group states. "We know there are lots of analytic techniques that can distort the findings," Dr. Miller told Medscape Medical News in an interview. "Gibbons was very selective in the studies that he chose to evaluate."  According to Dr. Miller, the use of mediation analysis in this instance broke the randomization and introduced bias. In spite of this, the findings still show that there is a statistically significant harmful direct effect of treatment on suicide risk in youth that is not discussed, he said.

"Even acknowledging that the technique he used could introduce bias and that he didn’t attempt to use techniques that have been around, trying to mitigate that potential bias, what he actually found but did not highlight in his paper is exactly what you’d expect from a study this size — namely, that there was a harmful effect of those who were put on antidepressants compared with those put on placebo.

"The finding didn’t reach statistical significance. He had a P value of 0.17, as opposed to less than 0.05, but that’s because he used very few people. So the direction of the effect did not reach statistical significance but was similar in magnitude and direction to what the FDA data showed — an increased risk of suicide among younger people. It is a statistic that he does not mention or highlight in his paper whatsoever," Dr. Miller said…

Just on the most superficial run through, the Gibbons meta-analysis is flawed. He used only the Eli Lilly child data to counter the FDA analysis of the whole world’s literature of Clinical Trials of Antidepressants in adolescents. And yet in his public speaking, he talks as if it stands for all antidepressants. He shows no data and presents an analysis no one can really understand or reproduce – essentially saying trust me! And yet his track record is of years of jumping onto any thread to debunk the Black Box warning – not just for antidepressants but for Neurontin as well [vote for marketing…].