SSRI's are they safe for adolescents?
In the first trial reanalyzed under the Restoring Invisible and Abandoned Trials (RIAT) initiative, the results contradict the original research findings that reported paroxetine to be a safe and effective treatment for major depression in adolescents.
The new research was published online in The BMJ.
Joanna Le Noury, PhD, of Bangor University in the United Kingdom, and colleagues reanalyzed the primary data from SmithKline Beecham's Study 329, published by Keller and colleagues in 2001, which had a primary objective of comparing the efficacy and safety of paroxetine and imipramine with that of placebo in the treatment of adolescents with unipolar major depression.
The reanalysis was done to determine whether access to, and reanalysis of, a full dataset from a randomized controlled trial would have a clinically relevant effect on evidence-based medicine.
The researchers found that the efficacy of paroxetine and imipramine was not statistically or clinically significantly different from placebo for any of the prespecified primary or secondary efficacy outcomes. HAM-D scores decreased by 10.7 (least squares mean) (95% confidence interval 9.1 to 12.3), 9.0 (7.4 to 10.5), and 9.1 (7.5 to 10.7) points, respectively, for the paroxetine, imipramine and placebo groups (P=0.20).
Clinically significant increases in harms, including suicidal ideation and behavior and other serious adverse effects, occurred in the paroxetine group while cardiovascular problems were reported in the imipramine group.
Conclusions: Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs. Access to primary data from trials has important implications for both clinical practice and research, including that published conclusions about efficacy and safety should not be read as authoritative.
"It is often said that science self corrects," writes the associate editor of The BMJ in an accompanying feature article. "But for those who have been calling for a retraction of the Keller paper for many years, the system has failed."
