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

BMJ 2005; 330 doi: https://doi.org/10.1136/bmj.330.7488.396 (Published 17 February 2005) Cite this as: BMJ 2005;330:396

Risk of Suicide Using SSRIs: Data Appears to be Incorrect

Fergusson et al (2004) report that the risk of suicide attempts is significantly greater for patients enrolled in short term RCTs of SSRIs compared with placebo (odds ratio of 2.28 p<_0.02 and="and" other="other" interventions="interventions" not="not" including="including" tricyclics="tricyclics" odds="odds" ratio="ratio" of="of" _1.94.b="_1.94.b"/>[1] Remarkably, they are also one of the few groups to report that completed suicide (fatal attempts) were also higher with SSRIs than tricyclics (odds ration 7.27). This appears to have led Geddes et al to state that there is almost a two risk of fatal and non-fatal risk of suicide for those taking SSRIs.[2]

An increased risk of fatal overdoses when using SSRIs is hard to understand, particularly when the comparison is tricyclics, given their acknowledged toxicity in overdose.[3-5] For this reason I re-checked the odds ratios from the data given by Fergusson, and found most of them to be incorrect. For example, the authors state that the odds of suicide attempts in SSRIs vs others is 1.94; but with 27 SSRI cases out of 4130 treated patients vs 18 control cases out of 4233 treated patients generates an odds of 1.54 (0.85-2.8) non-significant. Changing the denominator to 8856 and 9059 (all trials) makes no difference to the result. Similarly, the authors state that the odds for non-fatal attempts was 2.25 whereas I calculate it at 1.89 (0.96 –3.73) again non-significant. Perhaps most incomprehensibly regarding the odds of completed suicide vs tricyclics, the number of SSRI cases is 5 and TCA cases 4; obviously a non-significant difference. This is backed up by the calculation which reveals an odds of 1.1 (0.29-4.1) and not 7.27 as stated in the paper. This kind of error really does not help the debate in what is already a noisy area.

In conclusion either most of the raw data printed in table 1 is wrong; or one of us has miscalculated dramatically. I enclose a copy of my “working” for one of the above sums in case anyone else offers to clarify this.

Alex J Mitchell
Consultant in Liaison Psychiatry, Leicester General Hospital

Example Re-Calculation
Chi-square test (2 by 2)

Observed values and totals:

27 18

4103 4215 /8318

4130 4233 /8363

Expected values:

22.222887 22.777113 /
4107.777113 4210.222887

Uncorrected Chi² = 2.0398 P = 0.1532

Yates-corrected Chi² = 1.635152 P = 0.201

Measures of association:

Pearson's contingency = 0.015616
Cramér's V (signed) = 0.015618

References

[1] Fergusson D, Doucette S, Glass KC, Shapiro S, Healy D, Hebert P, et al. Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. BMJ 2005;330: 396-9.

[2]Andrea Cipriani, Corrado Barbui, and John R Geddes. Suicide, depression, and antidepressants BMJ 2005; 330: 373-374.

[3]Cheeta S, Schifano F, Oyefeso A, et al. Antidepressant-related deaths and antidepressant prescriptions in England and Wales, 1998-2000 BRIT J PSYCHIAT 2004 184: 41-47.

[4] Henry Ja, Alexander Ca, Sener Ek. Relative mortality from overdose of antidepressants. British medical journal 1995 310 (6974): 221-224.

[5] Shah R, Uren Z, Baker A, Majeed A. Deaths from antidepressants in England and Wales 1993-1997: analysis of a new national database. Psychological Medicine 2001: 31 (7): 1203-121.

Competing interests:
None declared

Competing interests: No competing interests

21 February 2005
Alex J Mitchell
Consultant in Liaison Psychiatry
Leicester General Hospital (UK)