Antidepressants and risk of abnormal bleeding research

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Vol. 164 No. 21, November 22, 2004 Arch Intern Med.

2004;164:2367-2370.

Association of Risk of Abnormal Bleeding With Degree of Serotonin

Reuptake Inhibition by Antidepressants

http://archinte.ama-assn.org/cgi/content/abstract/164/21/2367

Welmoed E. E. Meijer, PhD; Eibert R. Heerdink, PhD; Willem A. Nolen, MD,

PhD; Ron M. C. Herings, PhD; Hubert G. M. Leufkens, PharmD; Antoine C.

G. Egberts, PharmD

Background: Serotonin plays a role in platelet aggregation. Because

antidepressants influence blood serotonin levels, their use may be

associated with an increased risk of abnormal bleeding. However,

previous studies were inconclusive regarding this association. The aim

of this study was to estimate the risk of abnormal bleeding associated

with the use of antidepressants and to establish the relationship

between serotonin reuptake inhibition and the risk of bleeding.

Methods: We used data collected from 1992 through 2000 to conduct a

nested case-control study of a cohort of more than 64 000 new

antidepressant users. Cases were identified as all patients hospitalized

for a primary diagnosis of abnormal bleeding, and they were matched with

controls for age and sex. We classified exposure according to the degree

(high, intermediate, or low) of serotonin reuptake inhibition and

performed logistic regression analysis to calculate odds ratios.

Results: There were 196 cases of abnormal bleeding. The risk of

hospitalization increased with the use of inhibitors providing

intermediate (odds ratio, 1.9; 95% confidence interval, 1.1-3.5) and

high degrees of serotonin reuptake inhibition (odds ratio, 2.6; 95%

confidence interval, 1.4-4.8).

Conclusions: In a large population of new antidepressant users we found

a significant association between degree of serotonin reuptake

inhibition by antidepressants and risk of hospital admission for

abnormal bleeding as the primary diagnosis. An increased risk of

abnormal bleeding was strongly associated with the degree of serotonin

reuptake inhibition.

Author Affiliations: Department of Pharmacoepidemiology and

Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (Drs

Meijer, Heerdink, Herings, Leufkens, and Egberts) and Kendle

International (Dr Meijer), Utrecht, the Netherlands; Department of

Psychiatry, University Hospital Groningen, Groningen, the Netherlands

(Dr Nolen); PHARMO Institute for Drug Outcome Research, Utrecht (Dr

Herings); Hospital Pharmacy Midden-Brabant, TweeSteden and St beth

Hospital, Tilburg, the Netherlands (Dr Egberts).