Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort

Walraven, Carl van; Mamdani, Muhammad; Wells, Philip S.; Williams, Jessica

doi:10.1136/bmj.323.7314.655

Cited by 249 publications

(183 citation statements)

References 33 publications

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“…3 The difference between the 2 classifications is minor. We reanalyzed the data using the recently suggested classification and achieved highly comparable results for hemorrhagic and ischemic stroke (results not shown).…”

Section: Discussionmentioning

confidence: 99%

“…However, treatment with SSRIs has been associated with bleeding complications, 1 and it was recently shown that treatment with SSRIs increases the risk of upper gastrointestinal bleeding. 2,3 It is thus a major concern whether SSRIs also increase the risk of hemorrhagic stroke. A recent case-control study found no association between the use of SSRIs and the risk of intracranial hemorrhage (intracerebral, subarachnoidal, subdural, and unspecified intracranial hemorrhages).…”

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confidence: 99%

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Selective Serotonin Reuptake Inhibitors and the Risk of Stroke

Tsiropoulos

Kjærsgaard

et al. 2002

Stroke

125

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Background and Purpose-Selective serotonin reuptake inhibitors (SSRIs) have been associated with increased risk of bleeding complications, possibly as a result of inhibition of platelet aggregation. Little is known about the risk of intracerebral hemorrhage in users of SSRIs and whether the effect on platelet aggregation reduces the risk of ischemic stroke. We used population-based data to estimate the risk of hemorrhagic and ischemic stroke in users of SSRIs. Methods-We performed a nested case-control study in Funen County (465 000 inhabitants), Denmark. All patients with a first-ever stroke discharge diagnosis in the period of 1994 to 1999 were identified, and a validated diagnosis of stroke was reached in 4765 cases. In all, 40 000 controls were randomly selected from the background population. Information on drug use for cases and controls was retrieved from a prescription registry with full coverage of the county. Odds ratios were adjusted for age, sex, calendar year, and use of other medication. To evaluate the effect of various potential confounders not recorded in the register data, we performed separate analyses on data from 2 large population-based surveys with more detailed information on risk factors. Results-Of 659 patients with hemorrhagic stroke, 21 were current users of SSRIs. The adjusted odds ratio of hemorrhagic stroke in current SSRI users compared with never users was 1.0 [95% confidence interval (CI), 0.6 to 1.6]. Of 2717 patients with ischemic stroke, 100 were current users of SSRIs, and the adjusted odds ratio of ischemic stroke in cases compared with controls was 1.1 (95% CI, 0.9 to 1.4). The survey data indicated that additional confounder control would not have led to an increase in the relative risk estimates. Conclusions-Current exposure to SSRIs is not associated with increased risk of intracerebral hemorrhage and is probably not associated with a decreased risk of ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Selective Serotonin Reuptake Inhibitors and the Risk of Stroke

Tsiropoulos

Kjærsgaard

et al. 2002

Stroke

125

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“…5 The antiplatelet effects of SSRIs, most of which have high affinity for the serotonin transporter, have been implicated in an increased risk of gastrointestinal bleeding 6 and lower risk of MI among users of SSRIs. 7 Recently, van Walraven and colleagues 8 described an increased risk of upper gastrointestinal bleeding with increasing serotonin transporter affinity of antidepressants.…”

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confidence: 99%

Effect of Antidepressants and Their Relative Affinity for the Serotonin Transporter on the Risk of Myocardial Infarction

2003

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Background-Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), attenuate platelet activation by depleting serotonin storage and may decrease risk of myocardial infarction (MI). These drugs differ in their affinity for the platelet serotonin transporter and therefore may vary in their effects on MI protection. Methods and Results-A case-control study of first MI in patients aged 40 through 75 years was conducted among 36 hospitals in a 5-county area during a 3-year period. Case subjects were patients hospitalized with a first MI, and control subjects were randomly selected from the same geographic area. Detailed information regarding medication use and other clinical and demographic data were obtained by telephone interview. Among the 1080 cases and 4256 controls who participated, there were 223 users of antidepressants with high serotonin transporter affinity, all of which were SSRIs (paroxetine, fluoxetine, and sertraline). After adjustment with multivariable logistic regression for age, gender, race, education, physical activity, quantity of cigarettes smoked per day, body mass index, aspirin use, family history of MI, and history of diabetes, hypertension, or hypercholesterolemia, the odds ratio for MI among current users of antidepressants with high serotonin transporter affinity compared with nonusers was 0.

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“…The extent of the risk appears to correlate significantly with the extent of inhibition of serotonin reuptake. 17,18 The incidence of bruising/ecchymosis in premarketing trials of sibutramine was o1%. 7 Analysis of postmarketing data from the IMMP cohort also suggests that the risk of this adverse event is less than one in a hundred.…”

Section: Discussionmentioning

confidence: 99%

Bruising associated with sibutramine: results from postmarketing surveillance in New Zealand

2006

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Objective: To determine whether postmarketing data provide evidence of an association of sibutramine with bruising. Design and patients: During a postmarketing surveillance study of sibutramine in New Zealand by the Intensive Medicines Monitoring Programme (IMMP), a series of reports of bruising was identified. Further case reports were also obtained from the World Health Organisation (WHO) adverse drug reactions database. Outcome measures: All platelet, bleeding and clotting events associated with sibutramine were identified and causality assessments were performed. Results: From the IMMP and WHO databases a total of 16 cases of bruising that improved on withdrawal of sibutramine were identified. Of these, two had a recurrence of bruising on reintroduction of sibutramine. Conclusions: Evidence from postmarketing surveillance suggests that there is a causal association between sibutramine and bruising/ecchymosis. This represents a newly recognized adverse reaction for this medicine.

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Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort

Abstract: Objectives To determine the association between inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding.

Cited by 249 publications

References 33 publications

Selective Serotonin Reuptake Inhibitors and the Risk of Stroke

Selective Serotonin Reuptake Inhibitors and the Risk of Stroke

Effect of Antidepressants and Their Relative Affinity for the Serotonin Transporter on the Risk of Myocardial Infarction

Bruising associated with sibutramine: results from postmarketing surveillance in New Zealand

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