Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study

doi:10.1136/bmj.39041.445104.BE

BMJ 2007;334:242 (3 February), doi:10.1136/bmj.39041.445104.BE (published 12 December 2006)

Research

Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study

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

¹ RTI Health Solutions, Manchester Science Park, Manchester M15 6SE, ² RTI Health Solutions, Research Triangle Park, NC, USA, ³ Global Safety Surveillance and Epidemiology, Wyeth Research, PA, USA, ⁴ Warwick Medical School, University of Warwick, Coventry, ⁵ Pharmacoepidemiology and Risk Management, RTI Health Solutions, Research Triangle Park, USA

Correspondence to: A Rubino arubino{at}rti.org

Objective To compare the riskof suicide in adults using the antidepressant venlafaxine comparedwith citalopram, fluoxetine, and dothiepin.

Design Retrospective cohortstudy.

Setting UK General PracticeResearch Database.

Participants 219 088 patients,aged 18-89 years, who were prescribed venlafaxine, citalopram,fluoxetine, or dothiepin from 1995 to 2005.

Main outcome measures Completedsuicide and attempted suicide.

Results Venlafaxine users hada higher burden of risk factors for suicide, including previoussuicide attempts and proxies for severe depression or depressionthat was difficult to treat. In the analysis for completed suicides,unadjusted and adjusted hazard ratios for venlafaxine comparedwith citalopram were 2.44 (95% confidence interval 1.12 to 5.31)and 1.70 (0.76 to 3.80), for venlafaxine compared with fluoxetinewere 2.85 (1.37 to 5.94) and 1.63 (0.74 to 3.59), and for venlafaxinecompared with dothiepin were 2.54 (1.07 to 6.02) and 1.31 (0.53to 3.25). Compared with other study drugs, venlafaxine was alsoassociated with an increased risk of attempted suicide, butadjustment for measured confounders substantially reduced thehazard ratios.

Conclusions Venlafaxine usewas consistently associated with higher risk of suicide comparedwith citalopram, fluoxetine, and dothiepin. Venlafaxine usershad a higher burden of suicide risk factors, however, and adjustmentfor measured confounders substantially reduced the excess risks.Since the secondary data used in this analysis allowed onlyindirect and partial measurements of potential confounders,it is possible that residual confounding explains much, if notall, of the observed excess risk.

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