Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort studyBMJ 2007; 334 doi: https://doi.org/10.1136/bmj.39041.445104.BE (Published 01 February 2007) Cite this as: BMJ 2007;334:242
- Annalisa Rubino, director, epidemiology1,
- Neil Roskell, associate director, statistics1,
- Pat Tennis, senior director, epidemiology2,
- Daniel Mines, senior director, epidemiology3,
- Scott Weich, professor of psychiatry4,
- Elizabeth Andrews, vice president5
- 1RTI Health Solutions, Manchester Science Park, Manchester M15 6SE
- 2RTI Health Solutions, Research Triangle Park, NC, USA
- 3Global Safety Surveillance and Epidemiology, Wyeth Research, PA, USA
- 4Warwick Medical School, University of Warwick, Coventry
- 5Pharmacoepidemiology and Risk Management, RTI Health Solutions, Research Triangle Park, USA
- Correspondence to: A Rubino
- Accepted 7 November 2006
Objective To compare the risk of suicide in adults using the antidepressant venlafaxine compared with citalopram, fluoxetine, and dothiepin.
Design Retrospective cohort study.
Setting UK General Practice Research Database.
Participants 219 088 patients, aged 18-89 years, who were prescribed venlafaxine, citalopram, fluoxetine, or dothiepin from 1995 to 2005.
Main outcome measures Completed suicide and attempted suicide.
Results Venlafaxine users had a higher burden of risk factors for suicide, including previous suicide attempts and proxies for severe depression or depression that was difficult to treat. In the analysis for completed suicides, unadjusted and adjusted hazard ratios for venlafaxine compared with citalopram were 2.44 (95% confidence interval 1.12 to 5.31) and 1.70 (0.76 to 3.80), for venlafaxine compared with fluoxetine were 2.85 (1.37 to 5.94) and 1.63 (0.74 to 3.59), and for venlafaxine compared with dothiepin were 2.54 (1.07 to 6.02) and 1.31 (0.53 to 3.25). Compared with other study drugs, venlafaxine was also associated with an increased risk of attempted suicide, but adjustment for measured confounders substantially reduced the hazard ratios.
Conclusions Venlafaxine use was consistently associated with higher risk of suicide compared with citalopram, fluoxetine, and dothiepin. Venlafaxine users had a higher burden of suicide risk factors, however, and adjustment for measured confounders substantially reduced the excess risks. Since the secondary data used in this analysis allowed only indirect and partial measurements of potential confounders, it is possible that residual confounding explains much, if not all, of the observed excess risk.
Operational definitions and coding for suicides are on bmj.com
We thank William Irish and Ken Rothman for their contribution to the analysis, interpretation of the results, and preparation of the manuscript.
Contributors: AR, NR, PT, EA were responsible for the study design, data analysis, and interpretation, with contributions from DM and SW. AR and NR developed the study protocol. NR was responsible for the statistical analysis. AR, PT, and SW reviewed notes for the definition of completed and attempted suicides. AR wrote the paper, with contributions from all authors. EA is the guarantor.
Funding: This study was sponsored by Wyeth, which produces and markets venlafaxine. The contract between RTI Health Solutions and Wyeth specified that the authors at RTI Health Solutions had ultimate control over all aspects of the study, including control over publication. During the course of the study, however, any differences about the presentation or interpretation of findings that arose between the company author and external investigators were resolved through honest scientific debate. All authors had access to the statistical reports and tables supporting the publication.
Competing interests: All other authors have no personal financial interest in the drug studies. RTI Health Solutions has received research funding from several companies, including Lilly, GlaxoSmithKline, and Pfizer, who market antidepressants and potentially gain or lose financially from the results of the study.
Ethical approval: This study was approved by the institutional review board at RTI International and the General Practice Research Database Scientific and Ethical Advisory Group.
- Accepted 7 November 2006