Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study.
OBJECTIVE
To compare the risk of suicide in adults using the antidepressant venlafaxine compared with citalopram, fluoxetine, and dothiepin.


METHODS
Retrospective cohort study.


METHODS
UK General Practice Research Database.


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


METHODS
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.
Rubino
Annalisa
A
RTI Health Solutions, Manchester Science Park, Manchester M15 6SE. arubino@rti.org
Roskell
Neil
N
Tennis
Pat
P
Mines
Daniel
D
Weich
Scott
S
Andrews
Elizabeth
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects*; D015283:Citalopram / Q000009:adverse effects; D015331:Cohort Studies; D003511:Cyclohexanols / Q000009:adverse effects; D004308:Dothiepin / Q000009:adverse effects; D005473:Fluoxetine / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013405:Suicide / Q000706:statistics & numerical data*; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D003511:Cyclohexanols; D005473:Fluoxetine; D015283:Citalopram; D000069470:Venlafaxine Hydrochloride; D004308:Dothiepin