BMJ  2005;330:1148-1149 (14 May), doi:10.1136/bmj.330.7500.1148-b

Letter

Do selective serotonin reuptake inhibitors cause suicide?

Authors' reply to Curtin and Schulz, and Healy

EDITOR—We agree with Curtin and Schulz that drug induced motor disinhibition before mood improvement is a possible explanation for an excess of suicidal behaviour in the early weeks of antidepressant treatment.^{1 2}

Regarding their second point, we caution against over-interpreting differences in the pooled odds ratios for self harm and suicidal thoughts or the odds ratios for different selective serotonin reuptake inhibitors (SSRIs) in relation to the same end points. Odds ratios are estimated from a small number of events, and confidence intervals overlap.

Lastly, we agree that there is little evidence for a difference in risk between different classes of antidepressant.^3-5

Healy is concerned about two of the numbers in our meta-analysis. We confirm that the expert working group's report included one suicide among patients treated with placebo in placebo controlled trials of citalopram for depression (table 7.16, page 84).⁵ Likewise data on paroxetine suicides were reported (section 7.2.1, page 74).⁵ As we said in our paper, three of the four suicides in the placebo controlled trials of paroxetine (all in the placebo arm) occurred in the period after treatment. We therefore carried out sensitivity analysis to assess the effect on the pooled odds ratio of excluding these deaths (plus the suicide after treatment with escitalopram). This showed an increase in the odds ratio for suicide to 1.24. Healy's odds ratios are not calculated by using meta-analytic approaches for pooling data for

1149 each SSRI and so are not directly comparable with our figures.

We communicated Healy's concern with the paroxetine suicide data to the Medicines and Healthcare products Regulatory Agency (MHRA). In further consultation with the licence holder, the agency confirms that the four suicides in adult placebo controlled randomised trials of paroxetine were as described above (MHRA, personal communication, 2005).

Department of Social Medicine, University of Bristol, Bristol BS8 2PR D.J.Gunnell{at}bristol.ac.uk

Wolfson Institute of Preventive Medicine, Queen Mary, University of London, London EC1M 6BQ

---

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.

References

1. Healy D, Langmaak C, Savage M. Suicide in the course of the treatment of depression. J Psychopharmacol 1999;13: 94-9.[Abstract]
2. Nutt D. Death and dependence: current controversies over the selective serotonin reuptake inhibitors. J Psychopharmacol 2003;17: 355-64.[Abstract/Free Full Text]
3. Martinez C, Rietbrock S, Wise L, Ashby D, Chick J, Moseley J, et al. Antidepressant treatment and the risk of fatal and non-fatal self-harm in first episode depression—a nested case-control study. BMJ 2005;330: 389-93. (19 February.)[Abstract/Free Full Text]
4. Fergusson D, Doucette S, Cranley Glass K, Shapiro S, Healy D, et al. Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. BMJ 2005;330: 396-9. (19 February.)[Abstract/Free Full Text]
5. Report of the CSM expert working group on the safety of selective serotonin reuptake inhibitor antidepressants. www.mhra.gov.uk/news/2004/SSRIfinal.pdf (accessed 24 Apr 2005).

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

Related Articles

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]