BMJ  2005;330:396 (19 February), doi:10.1136/bmj.330.7488.396

Primary care

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

Dean Fergusson, scientist1, 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 dafergusson{at}ohri.ca

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.


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

Relevant Articles

The thinking doctor’s guide to placebos
Rudiger Pittrof and Ian Rubenstein
BMJ 2008 336: 1020. [Extract] [Full Text] [PDF]

Audit identifies the most read BMJ research papers
Susan Mayor
BMJ 2007 334: 554-555. [Extract] [Full Text] [PDF]

Did regulators fail over selective serotonin reuptake inhibitors?
David Healy
BMJ 2006 333: 92-95. [Full Text] [PDF]

FDA warns that antidepressants may increase suicidality in adults
Jeanne Lenzer
BMJ 2005 331: 70. [Extract] [Full Text]

Do selective serotonin reuptake inhibitors cause suicide?: Risk of suicide should be assessed for whole class of antidepressants
François Curtin and Pierre Schulz
BMJ 2005 330: 1148. [Extract] [Full Text] [PDF]

Do selective serotonin reuptake inhibitors cause suicide?: Authors' reply to Curtin and Schulz, and Healy
David Gunnell, Julia Saperia, and Deborah Ashby
BMJ 2005 330: 1148-1149. [Extract] [Full Text]

Do selective serotonin reuptake inhibitors cause suicide?: Discrediting old drugs may be useful in marketing new ones
Hugh M Jones
BMJ 2005 330: 1149. [Extract] [Full Text]

Do selective serotonin reuptake inhibitors cause suicide?: Let's keep it in perspective
Isaac Sakinofsky and David L Streiner
BMJ 2005 330: 1149. [Extract] [Full Text]

Do selective serotonin reuptake inhibitors cause suicide?: Data seem to be incorrect
Alex J Mitchell
BMJ 2005 330: 1149-1150. [Extract] [Full Text]

SSRIs and suicide: evidence supports the association
BMJ 2005 330: 0. [Full Text] [PDF]

Pills, thrills, and bellyaches
Kamran Abbasi
BMJ 2005 330: 0. [Extract] [Full Text] [PDF]

Suicide, depression, and antidepressants
Andrea Cipriani, Corrado Barbui, and John R Geddes
BMJ 2005 330: 373-374. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

  • Anderson, I., Ferrier, I., Baldwin, R., Cowen, P., Howard, L, Lewis, G, Matthews, K, McAllister-Williams, R., Peveler, R., Scott, J, Tylee, A (2008). Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2000 British Association for Psychopharmacology guidelines. J Psychopharmacol 22: 343-396 [Abstract]  
  • Deshauer, D. MD MSc, Moher, D. PhD, Fergusson, D. PhD, Moher, E. BA, Sampson, M. MLIS, Grimshaw, J. MD PhD (2008). Selective serotonin reuptake inhibitors for unipolar depression: a systematic review of classic long-term randomized controlled trials. CMAJ 178: 1293-1301 [Abstract] [Full text]  
  • Pittrof, R., Rubenstein, I. (2008). The thinking doctor's guide to placebos. BMJ 336: 1020-1020 [Full text]  
  • Erlangsen, A, Canudas-Romo, V, Conwell, Y (2008). Increased use of antidepressants and decreasing suicide rates: a population-based study using Danish register data. J. Epidemiol. Community Health 62: 448-454 [Abstract] [Full text]  
  • Olfson, M., Marcus, S. C., Druss, B. G. (2008). Effects of Food and Drug Administration Warnings on Antidepressant Use in a National Sample. Arch Gen Psychiatry 65: 94-101 [Abstract] [Full text]  
  • Posner, K., Oquendo, M. A., Gould, M., Stanley, B., Davies, M. (2007). Columbia Classification Algorithm of Suicide Assessment (C-CASA): Classification of Suicidal Events in the FDA's Pediatric Suicidal Risk Analysis of Antidepressants. Am. J. Psychiatry 164: 1035-1043 [Abstract] [Full text]  
  • Gibbons, R. D., Brown, C. H., Hur, K., Marcus, S. M., Bhaumik, D. K., Mann, J. J. (2007). Relationship Between Antidepressants and Suicide Attempts: An Analysis of the Veterans Health Administration Data Sets. Am. J. Psychiatry 164: 1044-1049 [Abstract] [Full text]  
  • Forrester, M.B. (2007). Escitalopram ingestions reported to Texas poison control centers, 2002 2005. Hum Exp Toxicol 26: 473-482 [Abstract]  
  • Leckband, S. G., Bishop, J. R., Ellingrod, V. L. (2007). Pharmacogenomics in Psychiatry. Journal of Pharmacy Practice 20: 252-264 [Abstract]  
  • Kurdyak, P. A., Juurlink, D. N., Mamdani, M. M. (2007). The Effect of Antidepressant Warnings on Prescribing Trends in Ontario, Canada. Am. J. Public Health 97: 750-754 [Abstract] [Full text]  
  • Cipriani, A., Geddes, J. R, Barbui, C. (2007). Venlafaxine for major depression. BMJ 334: 215-216 [Full text]  
  • Raymond, C. B., Morgan, S. G., Caetano, P. A. (2007). Antidepressant Utilization in British Columbia From 1996 to 2004: Increasing Prevalence but Not Incidence. Psychiatr. Serv. 58: 79-84 [Abstract] [Full text]  
  • Fischer, M. A., Servi, A. D., Polinski, J. M., Wang, P. S. (2007). Restrictions on Antidepressant Medications for Children: A Review of Medicaid Policy. Psychiatr. Serv. 58: 135-138 [Abstract] [Full text]  
  • Tiihonen, J., Lonnqvist, J., Wahlbeck, K., Klaukka, T., Tanskanen, A., Haukka, J. (2006). Antidepressants and the Risk of Suicide, Attempted Suicide, and Overall Mortality in a Nationwide Cohort. Arch Gen Psychiatry 63: 1358-1367 [Abstract] [Full text]  
  • Healy, D. (2006). The antidepressant tale: figures signifying nothing?. Adv. Psychiatr. Treat. 12: 320-327 [Abstract] [Full text]  
  • Ebmeier, K. P (2006). No apparent difference in suicide risk between older and newer antidepressants although older drugs may increase risk of suicide attempt during the first month of treatment.. Evid. Based Ment. Health 9: 82-82 [Full text]  
  • Olfson, M., Marcus, S. C., Shaffer, D. (2006). Antidepressant drug therapy and suicide in severely depressed children and adults: a case-control study.. Arch Gen Psychiatry 63: 865-872 [Abstract] [Full text]  
  • Healy, D. (2006). Did regulators fail over selective serotonin reuptake inhibitors?. BMJ 333: 92-95 [Full text]  
  • McHenry, L (2006). Ethical issues in psychopharmacology.. J. Med. Ethics 32: 405-410 [Abstract] [Full text]  
  • Juurlink, D. N., Mamdani, M. M., Kopp, A., Redelmeier, D. A. (2006). The Risk of Suicide With Selective Serotonin Reuptake Inhibitors in the Elderly. Am. J. Psychiatry 163: 813-821 [Abstract] [Full text]  
  • Mitchell, A J, Dennis, M (2006). Self harm and attempted suicide in adults: 10 practical questions and answers for emergency department staff.. Emerg. Med. J. 23: 251-255 [Abstract] [Full text]  
  • RESELAND, S., BRAY, I., GUNNELL, D. (2006). Relationship between antidepressant sales and secular trends in suicide rates in the Nordic countries. Br. J. Psychiatry 188: 354-358 [Abstract] [Full text]  
  • Baker, G. A. (2006). Depression and suicide in adolescents with epilepsy. Neurology 66: S5-S12 [Abstract] [Full text]  
  • Baldessarini, R. J., Pompili, M., Tondo, L. (2006). Suicidal risk in antidepressant drug trials.. Arch Gen Psychiatry 63: 246-248 [Full text]  
  • Mann, J. J., Apter, A., Bertolote, J., Beautrais, A., Currier, D., Haas, A., Hegerl, U., Lonnqvist, J., Malone, K., Marusic, A., Mehlum, L., Patton, G., Phillips, M., Rutz, W., Rihmer, Z., Schmidtke, A., Shaffer, D., Silverman, M., Takahashi, Y., Varnik, A., Wasserman, D., Yip, P., Hendin, H. (2005). Suicide Prevention Strategies: A Systematic Review. JAMA 294: 2064-2074 [Abstract] [Full text]  
  • Hansen, R. A., Gartlehner, G., Lohr, K. N., Gaynes, B. N., Carey, T. S. (2005). Efficacy and Safety of Second-Generation Antidepressants in the Treatment of Major Depressive Disorder. ANN INTERN MED 143: 415-426 [Abstract] [Full text]  
  • Leslie, L. K., Newman, T. B., Chesney, P. J., Perrin, J. M. (2005). The Food and Drug Administration's Deliberations on Antidepressant Use in Pediatric Patients. Pediatrics 116: 195-204 [Abstract] [Full text]  
  • Chou, R., Helfand, M. (2005). Challenges in Systematic Reviews That Assess Treatment Harms. ANN INTERN MED 142: 1090-1099 [Abstract] [Full text]  
  • Curtin, F., Schulz, P. (2005). Do selective serotonin reuptake inhibitors cause suicide?: Risk of suicide should be assessed for whole class of antidepressants. BMJ 330: 1148-1148 [Full text]  
  • Jones, H. M (2005). Do selective serotonin reuptake inhibitors cause suicide?: Discrediting old drugs may be useful in marketing new ones. BMJ 330: 1149-1149 [Full text]  
  • Gunnell, D., Saperia, J., Ashby, D. (2005). Do selective serotonin reuptake inhibitors cause suicide?: Authors' reply to Curtin and Schulz, and Healy. BMJ 330: 1148-1149 [Full text]  
  • Sakinofsky, I., Streiner, D. L (2005). Do selective serotonin reuptake inhibitors cause suicide?: Let's keep it in perspective. BMJ 330: 1149-1149 [Full text]  
  • Mitchell, A. J (2005). Do selective serotonin reuptake inhibitors cause suicide?: Data seem to be incorrect. BMJ 330: 1149-1150 [Full text]  
  • (2005). Do SSRIs Increase Suicide Risk in Adults?. Journal Watch Dermatology 2005: 10-10 [Full text]  
  • (2005). Antidepressants, Adults, and Suicidality. JWatch Women's Health 2005: 7-7 [Full text]  
  • (2005). Do SSRIs Increase Suicide Risk in Adults?. JWatch General 2005: 6-6 [Full text]  
  • (2005). SSRIs and Suicide Risk: A Concern for Adults, Too?. JWatch Psychiatry 2005: 1-1 [Full text]  
  • Cipriani, A., Barbui, C., Geddes, J. R (2005). Suicide, depression, and antidepressants. BMJ 330: 373-374 [Full text]  

Rapid Responses:

Read all Rapid Responses

Risk of Suicide Using SSRIs: Data Appears to be Incorrect
Alex J Mitchell
bmj.com, 21 Feb 2005 [Full text]
SSRI use and non-fatal self harm
Hugh M Jones
bmj.com, 22 Feb 2005 [Full text]
Antidepressants and Suicide: Let's Keep it in Perspective
Isaac Sakinofsky, et al.
bmj.com, 1 Mar 2005 [Full text]
SSRI's, why are we surprised?
Nicholas J O'Hara Smith
bmj.com, 2 Mar 2005 [Full text]
incorrectly lumping data
Dean A Fergusson
bmj.com, 4 Mar 2005 [Full text]
Antidepressants and Suicide: let's keep it in perspective
Isaac Sakinofsky, et al.
bmj.com, 8 Mar 2005 [Full text]
Risk of Suicide Using SSRIs: Further Clarification is Required
Alex J Mitchell
bmj.com, 9 Mar 2005 [Full text]
High risk fatal suicide attempts with SSRIs as compared wtih TCAs
Muhammad Muhsin Ahmad Zahari
bmj.com, 19 Mar 2005 [Full text]
corrected odds ratio for fatal suicide attempts with SSRIs as compared wtih TCAs
Dean A. Fergusson
bmj.com, 22 Mar 2005 [Full text]



Access all current jobs at BMJ Group
Whats new online at Student 

BMJ
Listen to the latest 

BMJ Interview