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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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Suicide and antidepressants: a comment

In an exhaustive Bayesian meta-analysis, Gunnell et al (1) explored
the suicide risk from pharmaceutical data on the different selective
serotonin reuptake inhibitors (SSRIs) currently on the market. Their
results give rise to some comments.

First, it has been observed by clinicians since the beginning of the use
of antidepressants that the first weeks of treatment of a severe
depression are accompanied by a higher risk of suicide, because of a drug-
induced motor disinhibition which is not yet accompanied by a mood
improvement. Probably a phenomenon such as akathisia mentioned by
Fergusson et al (2) adds up to the clinical picture. This element is
briefly mentioned by Gunnell et al (1) in the discussion but not
developed. During the first weeks of antidepressant treatment, patients
need to be closely monitored for this risk.

The global findings of a trend toward a protective effect of SSRI
concerning suicidal thoughts (pooled odds ratio (OR) 0.77) compared to a
trend towards an increased risk of self-harm (pooled OR 1.57) is somewhat
paradoxical even though the results are not statistically different. More
surprising is the heterogeneity of results among the different types of
SSRIs shown on the Figure. Why sertraline would show a protective effect
for suicidal thoughts and simultaneously increase the risk of self-harm?
Also strange is the difference of risks between citalopram and
escitalopram, while escitalopram is simply the active S-enantiomere of
citalopram. A difference of safety profile between the two compounds is
surprising. More generally, there is currently no strong biological
rationale to explain such heterogeneity in a pharmacological class of
drugs with the same mechanism of action.

In the Discussion, the authors mention also that according to a review by
the Medicine and Healthcare products Regulatory Agency (MHRA), there was
little evidence to show difference in the risk profile between SSRI and
other antidepressants. The two accompanying papers (2,3) show indeed that
the suicidal risk appears similar for SSRI and tricyclic antidepressants.

We think that this is an essential point and that the risk associated with
suicide should be assessed for the whole class of antidepressants.

The next stage would be to quantify the risk of suicide attempts according
to time since start of antidepressant. In terms of benefit-risk ratio,
there is probably an initial period where the risks are increased compared
to the benefits. It is only when the full improvement of the mood takes
place that the full benefit of antidepressants will be observed. It would
be interesting and useful to confirm by evidence-based methods the old
clinical observations.

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

2. Fergusson D, Doucette S, Cranley Glass K, Shapiro S, Healy D,
Hebert P, Hutton B. Association between suicide attempts and selective
serotonin reuptake inhibitors: systematic review of randomised controlled
trials BMJ 2005;330:396

3. Martinez C, Rietbrock S, Wise L, Ashby D, Chick J, Moseley J,
Evans S, Gunnell D Antidepressant treatment and the risk of fatal and non-
fatal self harm in first episode depression: nested case-control study.
BMJ 2005;330:389

Competing interests:
None declared

Competing interests: No competing interests

25 February 2005
Francois Curtin
Pierre Schulz
Clinical Psychopharmacology Unit, University of Geneva, CH-1225 Chene-Bourg/Geneva