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Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration

BMJ 2009; 339 doi: (Published 11 August 2009) Cite this as: BMJ 2009;339:b2880
  1. Marc Stone, medical officer,
  2. Thomas Laughren, director, division of psychiatry products,
  3. M Lisa Jones, medical officer,
  4. Mark Levenson, mathematical statistician,
  5. P Chris Holland, mathematical statistician,
  6. Alice Hughes, associate director for safety, division of neurology products,
  7. Tarek A Hammad, associate director, division of epidemiology,
  8. Robert Temple, associate director for medical policy,
  9. George Rochester, mathematical statistics team leader
  1. 1Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002, USA
  1. Correspondence to: Marc Stone marc.stone{at}
  • Accepted 1 May 2009


Objective To examine the risk of suicidal behaviour within clinical trials of antidepressants in adults.

Design Meta-analysis of 372 double blind randomised placebo controlled trials.

Setting Drug development programmes for any indication in adults.

Participants 99 231 adults assigned to antidepressants or placebo. Median age was 42 and 63.1% were women. Indications for treatment were major depression (45.6%), other depression (4.6%), other psychiatric disorders (27.6%), and non-psychiatric disorders (22.2%).

Main outcome measures Suicidal behaviour (completed suicide, attempted suicide, or preparatory acts) and ideation.

Results For participants with non-psychiatric indications, suicidal behaviour and ideation were extremely rare. For those with psychiatric indications, risk was associated with age. For suicidal behaviour or ideation and for suicidal behaviour only, the respective odds ratios were 1.62 (95% confidence interval 0.97 to 2.71) and 2.30 (1.04 to 5.09) for participants aged <25, 0.79 (0.64 to 0.98) and 0.87 (0.58 to 1.29) for those aged 25-64, and 0.37 (0.18 to 0.76) and 0.06 (0.01 to 0.58) for those aged ≥65. When age was modelled as a continuous variable, the odds ratio for suicidal behaviour or ideation declined at a rate of 2.6% per year of age (−3.9% to −1.3%, P=0.0001) and the odds ratio for suicidal behaviour declined at a rate of 4.6% per year of age (−7.4% to −1.8%, P=0.001).

Conclusions Risk of suicidality associated with use of antidepressants is strongly age dependent. Compared with placebo, the increased risk for suicidality and suicidal behaviour among adults under 25 approaches that seen in children and adolescents. The net effect seems to be neutral on suicidal behaviour but possibly protective for suicidal ideation in adults aged 25-64 and to reduce the risk of both suicidality and suicidal behaviour in those aged ≥65.


  • We thank Renmeet Grewal, William Bender, and Paul David for their administrative and organisational support for this project.

  • Contributors: MS was responsible for statistical design, analysis, and writing of the manuscript and is guarantor. TL and AH planned and conducted the analysis and contributed to the writing of the manuscript. MLJ prepared the methods section of the manuscript and data for analysis. ML was responsible for statistical design and reviewed the manuscript. PCH was responsible for data analysis and reviewed the manuscript. TAH planned and executed this study and reviewed the manuscript. RT wrote and edited the manuscript and contributed to the analysis. GR was responsible for statistical methods and overall analytical approaches.

  • Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

  • Competing interests: None declared.

  • Ethical approval: Not required.

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