- Dean Fergusson, scientist ()1,
- Steve Doucette, research associate1,
- Kathleen Cranley Glass, associate professor2,
- Stan Shapiro, professor3,
- David Healy, professor4,
- Paul Hebert, senior scientist1,
- Brian Hutton, research associate1
- 1 Ottawa Health Research Institute, Clinical Epidemiology Program, 501 Smyth Road, Box 201, Ottawa, Ontario, Canada K1H 8L6
- 2 Departments of Human Genetics and Pediatrics and Biomedical Ethics Unit, McGill University, Montreal, Quebec, Canada
- 3 Department of Epidemiology and Biostatistics, McGill University
- 4 Department of Psychological Medicine, University of Wales College of Medicine, Bangor
- Correspondence to: D Fergusson
- Accepted 4 January 2005
Objective To establish whether an association exists between use of selective serotonin reuptake inhibitors (SSRIs) and suicide attempts.
Design Systematic review of randomised controlled trials.
Data sources Medline and the Cochrane Collaboration's register of controlled trials (November 2004) for trials produced by the Cochrane depression, anxiety, and neurosis group.
Selection of studies Studies had to be randomised controlled trials comparing an SSRI with either placebo or an active non-SSRI control. We included clinical trials that evaluated SSRIs for any clinical condition. We excluded abstracts, crossover trials, and all trials whose follow up was less than one week.
Results Seven hundred and two trials met our inclusion criteria. A significant increase in the odds of suicide attempts (odds ratio 2.28, 95% confidence 1.14 to 4.55, number needed to treat to harm 684) was observed for patients receiving SSRIs compared with placebo. An increase in the odds ratio of suicide attempts was also observed in comparing SSRIs with therapeutic interventions other than tricyclic antidepressants (1.94, 1.06 to 3.57, 239). In the pooled analysis of SSRIs versus tricyclic antidepressants, we did not detect a difference in the odds ratio of suicide attempts (0.88, 0.54 to 1.42).
Discussion Our systematic review, which included a total of 87 650 patients, documented an association between suicide attempts and the use of SSRIs. We also observed several major methodological limitations in the published trials. A more accurate estimation of risks of suicide could be garnered from investigators fully disclosing all events.
Contributors DF conceived the study. DF, SD, KG, and SS designed the study. DF and SD collected, managed, and analysed the data. All authors interpreted the data and contributed to the writing of the paper. DF is the guarantor.
Funding Canadian Institutes of Health Research.
Competing interests DH has had consultancies with, been a principal investigator or clinical trialist for, been a chairman or speaker at international symposia for, or been in receipt of support to attend foreign meetings from: Astra, Astra-Zeneca, Boots/Knoll, Eli Lilly, Janssen-Cilag, Lorex-Synthelabo, Lundbeck, Organon, Pharmacia & Upjohn, PierreFabre, Pfizer, Rhone-Poulenc Rorer, Roche, SmithKline Beecham, Solvay, and Zeneca. DH has been an expert witness for the plaintiff in eight legalactions involving SSRIs and has been consulted on several cases of attempted suicide, suicide, and suicide-homicide after antidepressant medication, in most of which he has offered the view that the treatment was not involved. He has also been an expert witness for the defendants (the British NHS) in a large series of lysergic acid diethylamide (LSD) and electroconvulsive therapy (ECT) cases.
- Accepted 4 January 2005