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Fluoxetine Does Not Cause A Statistically Significant Increase in Risk of Suicidal Events in Depressed Adolescents, Though Adequately Powered Studies are Still Needed


  • Does treatment with fluoxetine increase the risk of suicidal behavior or completed suicides in adolescents with major depressive disorder?

Clinical Bottom Lines

  1. Fluoxetine may still be a very useful and effective part of treatment for depressed adolescents, despite the FDA black box warning against SSRI use in children.
  2. Fluoxetine should be the only SSRI used for adolescents with depression, as it has the safest side effect profile and is the only SSRI approved for this indication.
  3. There is some weak evidence that treatment with fluoxetine MAY cause some increase in "harm-related" behaviors, so patients on SSRIs (including fluoxetine) should be monitored closely for changes or increases in suicidal ideation or aggressive behavior.

Summary of Key Evidence

  1. This is the first large study, since FDA black box warnings came out, to address use of SSRIs in depressed adolescents.1
  2. Number needed to harm was calculated for "harm-related events" defined as events which include aggression, increased suicidal ideation, and increased non-lethal suicidal behavior: Number Needed to Harm (NNH)= 16 patients treated to cause one more harm-related event (95% CI = 6 to 643).
  3. Number needed to harm was also calculated for "suicide-related events"' defined as events which include suicide attempts or increases in suicidal ideation, this is a subset of the events included in "harm-related" events: NNH = 31, (95% CI = 8 to NNT 106). This can be interpreted as 31 patients treated to cause one more harm related event, but 95% CI crosses from NNH of 8 to NNT of 106 (which would reflect a decrease in these events on patients on fluoxetine).

Additional Comments

  • While this is the largest, and most targeted study currently published, the results in terms of risk of increased suicidal events/attempts are probably not significant enough to direct treatment, especially because the study was powered to detect a difference in efficacy between treatment groups, not to detect a difference in suicide-related events. This was a secondary measured variable.
  • In retrospective analysis of patients: "all but 1 of the 7 participants who attempted suicide (1.6% of the study patients) met SIQ-Jr criteria for clinically significant suicidal ideation at baseline, suggesting that this finding might be related to an imbalance across treatment groups in risk for suicide at baseline."


  1. TADS Team. Fluoxetine, cognitive behavioral therapy, and their combination for adolescents with depression. JAMA 2004; 292: 807-820.

CAT Author: Karen R. Fauman, MD

CAT Appraisers: Stephen Park, MD

Date appraised: March 22, 2006

Last updated November 28, 2006
Department of Pediatrics and Communicable Diseases
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