Users of SSRIs face risk of abnormal bleeding
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《英国医生杂志》
Users of selective serotonin reuptake inhibitors (SSRI) face an increased risk of abnormal bleeding, which increases with the potency of their serotonin reuptake inhibition (Arch Intern Med 2004;164:2367-70).
Serotonin has long been known to play a role in platelet aggregation. Because antidepressants influence blood serotonin levels, some researchers have postulated that their use may lead to an increased risk of abnormal bleeding, but the previous studies that looked at this question were inconclusive.
To test this hypothesis, researchers from the department of pharmacoepidemiology and pharmacotherapy at the Utrecht Institute for Pharmaceutical Sciences in Utrecht, the Netherlands, and their colleagues used data collected from 1992 to 2000 to conduct a nested case-control study of a group of more than 64 000 patients using antidepressants for the first time.
The data were collected from the PHARMO database, which contained the prescription medication histories for more than 850 000 patients in the Netherlands. To be included in the study, patients had to have been taking an SSRI for at least 30 days. To be counted as a case, they had to have stopped taking the drug for no more than 30 days after experiencing abnormal bleeding.
The researchers matched prescription data to hospital discharge data and identified cases as patients admitted to hospital for a primary diagnosis of abnormal bleeding while taking an SSRI. Controls were matched for age and sex. The cases were further classified according to the degree of serotonin reuptake inhibition they were exposed to—high, intermediate, or low, depending on the known potency of the drug they were on, which was defined as the drug抯 binding affinity for the serotonin transporter.
The researchers identified 196 cases of abnormal bleeding, which included uterine bleeding, bleeding in the upper gastrointestinal tract, cerebral bleeding, haematuria, nose bleeds, haemoptosys, haemarthrosis, haematoma, and excessive bleeding after surgery. They found that the risk of admission to hospital from one of these conditions increased with the use of inhibitors that provided intermediate (odds ratio 1.9, 95% confidence interval 1.1 to 3.5) and high levels of serotonin reuptake inhibition (2.6, 1.4 to 4.8).
They also analysed subgroups with abnormal uterine bleeding, and although the results were not significant, they found an increased risk of abnormal uterine bleeding in women using antidepressants with intermediate (adjusted odds ratio 1.7, 0.7 to 4.1) and high (3.0, 0.8 to 4.9) levels of inhibition of serotonin reuptake compared with women using antidepressants with low levels of inhibition.
The researchers say they probably missed bleeding events that did not result in admission hospital or that resulted in death before the patient came to hospital, which most likely led them to underestimate the actual risk.
"Our results show that a higher degree of inhibition of serotonin reuptake is associated with a higher risk of admission for various categories of bleeding, indicating a similar underlying pharmacological action" the authors wrote. "This study broadens the view of the previously reported associations between the use of antidepressants and bleeding."(New York Scott Gottlieb)
Serotonin has long been known to play a role in platelet aggregation. Because antidepressants influence blood serotonin levels, some researchers have postulated that their use may lead to an increased risk of abnormal bleeding, but the previous studies that looked at this question were inconclusive.
To test this hypothesis, researchers from the department of pharmacoepidemiology and pharmacotherapy at the Utrecht Institute for Pharmaceutical Sciences in Utrecht, the Netherlands, and their colleagues used data collected from 1992 to 2000 to conduct a nested case-control study of a group of more than 64 000 patients using antidepressants for the first time.
The data were collected from the PHARMO database, which contained the prescription medication histories for more than 850 000 patients in the Netherlands. To be included in the study, patients had to have been taking an SSRI for at least 30 days. To be counted as a case, they had to have stopped taking the drug for no more than 30 days after experiencing abnormal bleeding.
The researchers matched prescription data to hospital discharge data and identified cases as patients admitted to hospital for a primary diagnosis of abnormal bleeding while taking an SSRI. Controls were matched for age and sex. The cases were further classified according to the degree of serotonin reuptake inhibition they were exposed to—high, intermediate, or low, depending on the known potency of the drug they were on, which was defined as the drug抯 binding affinity for the serotonin transporter.
The researchers identified 196 cases of abnormal bleeding, which included uterine bleeding, bleeding in the upper gastrointestinal tract, cerebral bleeding, haematuria, nose bleeds, haemoptosys, haemarthrosis, haematoma, and excessive bleeding after surgery. They found that the risk of admission to hospital from one of these conditions increased with the use of inhibitors that provided intermediate (odds ratio 1.9, 95% confidence interval 1.1 to 3.5) and high levels of serotonin reuptake inhibition (2.6, 1.4 to 4.8).
They also analysed subgroups with abnormal uterine bleeding, and although the results were not significant, they found an increased risk of abnormal uterine bleeding in women using antidepressants with intermediate (adjusted odds ratio 1.7, 0.7 to 4.1) and high (3.0, 0.8 to 4.9) levels of inhibition of serotonin reuptake compared with women using antidepressants with low levels of inhibition.
The researchers say they probably missed bleeding events that did not result in admission hospital or that resulted in death before the patient came to hospital, which most likely led them to underestimate the actual risk.
"Our results show that a higher degree of inhibition of serotonin reuptake is associated with a higher risk of admission for various categories of bleeding, indicating a similar underlying pharmacological action" the authors wrote. "This study broadens the view of the previously reported associations between the use of antidepressants and bleeding."(New York Scott Gottlieb)