Objective: The aim of this study was to assess whether unpublished trials of serotonin reuptake inhibitors in pediatric depression impacted efficacy or safety conclusions, and to examine the evolution of information contributing to the safety/efficacy debate.
Method: From 939 potentially relevant studies extracted from Medline, Cinahl, Biosis, and Cochrane databases, and from the United Kingdom's Committee on Safety of Medicines website, we examined 38 studies: Ten published and five unpublished randomized, controlled trials, 22 observational studies, and one crossover trial. We performed cumulative and noncumulative meta-analyses and generated pooled relative rates of response and serious adverse events for high-quality randomized, controlled trials.
Results: Unpublished studies did not substantially alter the risk-to-benefit determination. Cumulative meta-analyses of seven randomized, controlled trials for efficacy and 11 randomized, controlled trials for safety suggest an adverse safety/efficacy profile for selective serotonin reuptake inhibitors (SSRIs) overall. Fluoxetine and citalopram appear to offer favorable risk to benefit profiles, while shorter-acting agents pose greater risks and provide marginal benefit.
Conclusions: While simple meta-analysis across all SSRIs for treatment of pediatric depression provided general efficacy and safety information, meta-analysis of individual drugs and use of cumulative meta-analytic techniques may have expedited our ability to formulate conclusions about safety and efficacy of SSRIs in pediatric depression.
