By Peter C Gøtzsche
Psychiatrist David Healy and I have restored the two pivotal fluoxetine trials in children and adolescents with depression, which led to approval of this drug for minors. This drug, or any other depression pill, should never have been approved for children, as they do not work and double the risk of suicide. Here is our full report and the abstract is below. I also provide the peer review comments and our replies, as they tell a story about the first peer reviewer being so blind that he or she WILL NOT SEE. This denial, which is very common in psychiatry, has tragic consequences for our children. I have uploaded the two clinical study reports Eli Lilly submitted to the UK drug regulator that we used for our research, and also the statistical review and the medical review by the FDA.
BACKGROUND: Fluoxetine was approved for depression in children and adolescents based on two placebo-controlled trials, X065 and HCJE, with 96 and 219 participants, respectively.
OBJECTIVE: To review these trials, which appear to have been misreported.
METHODS: Systematic review of the clinical study reports and publications. The primary outcomes were the efficacy variables in the trial protocols, suicidal events, and precursors to suicidality or violence.
RESULTS: Essential information was missing and there were unexplained numerical inconsistencies. The efficacy outcomes were biased in favour of fluoxetine by differential dropouts and missing data. The efficacy on the Children’s Depression Rating Scale-Revised was 4% of the baseline score, which is not clinically relevant. Patient ratings did not find fluoxetine effective. Suicidal events were missing in the publications and the study reports. Precursors to suicidality or violence occurred more often on fluoxetine than on placebo. For trial HCJE, the number needed to harm was 6 for nervous system events, 7 for moderate or severe harm, and 10 for severe harm. Fluoxetine reduced height and weight over 19 weeks by 1.0 cm and 1.1 kg, respectively, and prolonged the QT interval.
CONCLUSIONS: Our reanalysis of the two pivotal trials showed that fluoxetine is unsafe and ineffective.