Craig J Whittington, Tim Kendall, Peter Fonagy, David
Cottrell, Andrew Cotgrove, Ellen Boddington
Centre for Outcomes Research and Effectiveness, Subdepartment
of Clinical Health Psychology, University College London, 1-19
Torrington Place, London WC1E 7HB, UK (C J Whittington PhD, Prof
P Fonagy PhD, E Boddington MSc); Royal College of Psychiatrists'
Research Unit, London SW1H 0HW (T Kendall MRCPsych); Academic
Unit of Child and Adolescent Mental Health, School of Medicine,
University of Leeds, Leeds, UK (Prof D Cottrell FRCPsych);
and Pine Lodge Young People's Centre, Chester, UK (A Cotgrove
MRCPsych)
Correspondence to: Dr Craig Whittington (e-mail:c.whittington@ucl.ac.uk)
Background Questions concerning the safety of
selective serotonin reuptake inhibitors (SSRIs) in the treatment of
depression in children led us to compare and contrast published and
unpublished data on the risks and benefits of these drugs.
Methods We did a meta-analysis of data from randomised
controlled trials that evaluated an SSRI versus placebo in
participants aged 5-18 years and that were published in a
peer-reviewed journal or were unpublished and included in a review
by the Committee on Safety of Medicines. The following outcomes were
included: remission, response to treatment, depressive symptom
scores, serious adverse events, suicide-related behaviours, and
discontinuation of treatment because of adverse events.
Findings Data for two published trials suggest that
fluoxetine has a favourable risk-benefit profile, and unpublished
data lend support to this finding. Published results from one trial
of paroxetine and two trials of sertraline suggest equivocal or weak
positive risk-benefit profiles. However, in both cases, addition of
unpublished data indicates that risks outweigh benefits. Data from
unpublished trials of citalopram and venlafaxine show unfavourable
risk-benefit profiles.
Interpretation Published data suggest a favourable
risk-benefit profile for some SSRIs; however, addition of
unpublished data indicates that risks could outweigh benefits of
these drugs (except fluoxetine) to treat depression in children and
young people. Clinical guideline development and clinical decisions
about treatment are largely dependent on an evidence base published
in peer-reviewed journals. Non-publication of trials, for whatever
reason, or the omission of important data from published trials, can
lead to erroneous recommendations for treatment. Greater openness
and transparency with respect to all intervention studies is needed.
Lancet 2004;
363: 1341-45
See Commentary 
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