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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

BMJ 2005; 330 doi: (Published 17 February 2005) Cite this as: BMJ 2005;330:385

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Suicidal behaviour and SSRIs - updated meta-analysis

Dear Editor,


Last year you
published our article on the risk of suicide from selective serotonin reuptake
inhibitors (SSRIs).
1 In the light of recently released data for
paroxetine by its manufacturer GlaxoSmithKline
2 we wish to update our results.


In our original
analysis, we were unable to distinguish between occurrences of non-fatal self
harm and suicidal thoughts for patients in paroxetine trials. Our main analysis
of these events therefore excluded the paroxetine data; in a sensitivity
analysis we divided the events equally between self harm and suicidal thoughts.
The new data released by GlaxoSmithKline come from placebo controlled trials of
paroxetine and combine data on completed suicides, attempted suicide and
preparatory acts towards imminent suicidal behaviour
into a single category of “definitive suicidal behaviour”.
For consistency with our original article, we have used data on all
indications, although GlaxoSmithKline have provided a full breakdown. In 57
trials, there were 50/8958 events in the paroxetine arm and 40/5953 in the
placebo arm. The newly released data suggest the figures in relation to
suicidal thoughts were 33/8958 for paroxetine and 25/5953 for placebo. There is
no new information on completed suicides.


We have used the
newly available data to update our meta-analysis. Our findings are similar to
those in our published paper.


Using the same
Bayesian random effects meta-analysis as before, the odds ratio for non-fatal
self harm in patients taking an SSRI compared to placebo is 1.21 (95% credible
interval 0.87 to 1.83). For suicidal thoughts, we have an odds ratio of 0.80
(95% credible interval 0.49 to 1.30). The previous results were an odds ratio
1.57 (95% credible interval 0.99 to 2.55) for self harm and an odds ratio of 0.77 (95% credible interval 0.37 to 1.55) for suicidal thoughts. The results suggest
that the overall effect on non-fatal self harm is reduced compared to our
previous estimate, and slightly increased for suicidal thoughts. As before,
this analysis is limited by the length of the trials and inconsistent
collection of safety endpoints. More evidence is needed to reliably assess
specific adverse effects of SSRIs in relation to
their use in particular disorders such as the increased risk of self harm
recently reported for paroxetine in major depressive disorder.
3 We feel that it is worth bringing this to the
attention of your readers. Updated tables and figures are available on request.


   1.   Gunnell D, Saperia J, Ashby D. Selective
serotonin reuptake inhibitors (SSR1s) and suicide in adults: meta-analysis of
drug company data from placebo controlled, randomised controlled trials
submitted to the MHRA's safety review. BMJ. 2005;330:385-388A.

  GlaxoSmithKline. Paroxetine and Adult Patients - 2006
(accessed 10 May 2006).


3.      Duff
G. Letter to clinical colleagues in
relation to "Paroxetine (Seroxat)
– risk of suicidal behaviour in adults".  (accessed 23 May

Competing interests:
DG and DA were members of the MHRA's expert working group on the safety of SSRIs. They acted as independent advisers, receiving travel expenses and a small fee for meeting attendance and reading materials in preparation for the meeting. DA has spoken on the methods of adverse drugs reactions in HIV at a scientific meeting attended by several pharmaceutical companies, and sponsored by GlaxoSmithKline. An honorarium was paid to her department.

Competing interests: No competing interests

02 June 2006
Julia Saperia
Research Assistant
Deborah Ashby, David Gunnell
Wolfson Institute of Preventive Medicine, Queen Mary, University of London, EC1M 6BQ