Editor—Our meta-analysis on the risk of suicide from selective serotonin reuptake inhibitors (SSRIs) was published last year.1 In the light of recently released data for paroxetine by its manufacturer, GlaxoSmithKline,2 we have updated 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 has 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.
Our updated findings are similar to those published.
Using the same bayesian random effects meta-analysis as before, the odds ratio for non-fatal self harm in patients taking an SSRI compared with placebo is 1.21 (95% credible interval 0.87 to 1.83). For suicidal thoughts the odds ratio is 0.80 (0.49 to 1.30). The previous results were 1.57 (0.99 to 2.55) for self harm and 0.77 (0.37 to 1.55) for suicidal thoughts. The results suggest that the overall effect on non-fatal self harm is reduced compared with 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 end points. 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
Updated tables and figures are available on request.
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.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: 385-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.GlaxoSmithKline. Paroxetine and adult patients—2006 analysis. www.gsk.com/media/par_current_analysis.htm (accessed 10 May 2006).
- 3.Duff G. Letter to clinical colleagues in relation to “Paroxetine (Seroxat) - risk of suicidal behaviour in adults.” www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dID=20961&noSaveAs=1&Rendition=WEB (accessed 23 May 2006).