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Review: most selective serotonin reuptake inhibitors lead to adverse events that appear to outweigh the benefits in children
  1. E Jane Garland, MD, FRCPC
  1. University of British Columbia, Vancouver, British Columbia, Canada

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 Q Are selective serotonin reuptake inhibitors (SSRIs) safe and effective for treating depression in children?

    Clinical impact ratings Mental health ★★★★★★☆ Psychiatry ★★★★★★☆ Paediatrics ★★★★★★☆ GP/FP/Primary care ★★★★★★☆


    Embedded ImageData sources:

    Medline, CINAHL, EMBASE/Excerpta Medica, and PsycINFO (to April 2003); Cochrane Library; reference lists; tables of contents; previous systematic reviews; Guideline Development Group information; and written requests to experts.

    Embedded ImageStudy selection and assessment:

    English language randomised controlled trials (RCTs) or RCTs with English abstracts that compared SSRIs with placebo in children (5–18 y) with depression; had adequate blinding, concealed allocation, and a description of withdrawals; and were published in peer reviewed journals or reviewed by the Committee on Safety of Medicines.

    Embedded ImageOutcomes:

    adverse events, remission, response, and mean depression level.


    6 published and 6 unpublished RCTs were reviewed. Fluoxetine showed a benefit for remission and response, and the adverse event data were not statistically significant (table). Paroxetine increased remission but not response and increased serious adverse events (table). Sertraline did not show a benefit for remission and led to more dropouts because of adverse events (table); a treatment effect for response had borderline significance. Citalopram led to a small reduction in depressive symptoms, and venlafaxine had no effect; adverse events were increased for both drugs (table).

    Selective serotonin reuptake inhibitors (SSRIs) v placebo for depression in children*


    In children with depression, fluoxetine improves symptoms without increasing adverse events. For paroxetine, sertraline, venlafaxine, and citalopram, the risks appear to outweigh the benefits.

    A modified version of this abstract appears in Evidence-Based Nursing.


    Whittington et al have highlighted 3 key issues in the evaluation of the evidence base for antidepressant treatment in children and adolescents: effectiveness, safety, and the role of access to published versus unpublished data. A consistently high placebo response is noted, which emphasises the importance of undertaking controlled clinical trials for antidepressants in young people rather than assuming efficacy based on adult studies. Adverse effects also appear to be higher in children. The authors concluded that except for fluoxetine, the evidence does not support a favourable risk-benefit balance for SSRIs in child and adolescent depression. In addition to including unpublished negative trials, Whittington et al also criticised the interpretation of marginal results to produce apparently positive published studies (eg, sertraline, paroxetine) which, on reanalysis, do not show effectiveness and for which the impact of the risk-benefit ratio has also been ignored. The authors’ conclusions are essentially the same as those reached by regulatory agencies that had access to the full data set1,2 and by other authors who have reviewed the published studies.3,4 This review illustrates the problem of publication bias in “evidence-biased medicine,”5 which includes biased interpretation of published data in favour of the drug and inability to weigh the full body of evidence because of lack of access to unpublished data.


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    • For correspondence: Dr C Whittington, University College London, London, UK.

    • Source of funding: no external funding.