Published 11 August 2009, doi:10.1136/bmj.b2880
Cite this as: BMJ 2009;339:b2880

Research

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

¹ Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002, USA

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.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    StumbleUpon    Technorati    Twitter    What's this?

Relevant Articles

Risk of suicidal behaviour in adults taking antidepressants

John Richard Geddes, Corrado Barbui, and Andrea Cipriani
BMJ 2009 339: b3066. [Extract] [Full Text]

Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review

David Gunnell, Julia Saperia, and Deborah Ashby
BMJ 2005 330: 385. [Abstract] [Full Text] [PDF]

Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: nested case-control study

Carlos Martinez, Stephan Rietbrock, Lesley Wise, Deborah Ashby, Jonathan Chick, Jane Moseley, Stephen Evans, and David Gunnell
BMJ 2005 330: 389. [Abstract] [Full Text] [PDF]

Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials

Dean Fergusson, Steve Doucette, Kathleen Cranley Glass, Stan Shapiro, David Healy, Paul Hebert, and Brian Hutton
BMJ 2005 330: 396. [Abstract] [Full Text] [PDF]

Related external webpages:

Listen to an audio interview with Marc Stone, in the BMJ podcast.

This article has been cited by other articles:

• Barbui, C., Cipriani, A., Furukawa, T. A, Salanti, G., Higgins, J. P T, Churchill, R., Watanabe, N., Nakagawa, A., Omori, I. M, Geddes, J. R (2009). Making the best use of available evidence: the case of new generation antidepressants: A response to: Are all antidepressants equal?. Evid. Based Ment. Health 12: 101-104 [Full text]  
• Geddes, J. R., Barbui, C., Cipriani, A. (2009). Risk of suicidal behaviour in adults taking antidepressants. BMJ 339: b3066-b3066 [Full text]  

Rapid Responses:

Read all Rapid Responses

Suicidal thoughts and actions versus completed suicide

Paula J Clayton, MD, et al.
bmj.com, 20 Aug 2009 [Full text]

depressants and suicide

Billy Levin
bmj.com, 20 Aug 2009 [Full text]

Age and anti- depressants-the statistical dilemma

Zekria Ibrahimi
bmj.com, 21 Aug 2009 [Full text]

Risk of Suicidality (Sic)

Derek HALL
bmj.com, 22 Aug 2009 [Full text]

Beware of pharmaceutical company bias.

Sumeet Gupta
bmj.com, 24 Aug 2009 [Full text]

Not the last word

David Healy
bmj.com, 26 Aug 2009 [Full text]

Not the last word

David Healy
bmj.com, 28 Aug 2009 [Full text]

Author's Reply

Marc B Stone, et al.
bmj.com, 27 Aug 2009 [Full text]

Author's reply

Marc B Stone, et al.
bmj.com, 27 Aug 2009 [Full text]

The safety issue - what about total mortality ?

Nir Tsabar
bmj.com, 31 Aug 2009 [Full text]

Authors' reply

Marc B Stone
bmj.com, 2 Sep 2009 [Full text]

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

Robert D. Gibbons, et al.
bmj.com, 22 Sep 2009 [Full text]

Suicide "Attempts"--So What?

Donald J. Farber
bmj.com, 26 Sep 2009 [Full text]

Online poll

Find out more>>