Antidepressant use linked to slightly increased risk for subdural hematoma
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Use of selective and nonselective serotonin reuptake inhibitors appeared associated with a small increased risk for subdural hematoma, according to results of a nationwide, case-control study.
Of note, subdural hematoma risk appeared restricted to the first year of treatment.
Ultimately, researchers deemed the overall risk small — indicating low likelihood for drug-drug interaction — except in the case of triple use of antidepressants, NSAIDs and vitamin K antagonists.
“Dual treatment of antidepressants and co-medication purported to increase bleeding risk was not associated with higher risks than expected from the co-medication in question,” David Gaist, PhD, researcher in the department of clinical research at University of Southern Denmark, and colleagues wrote.
Since the 1980s, subdural hematoma incidence has increased steadily. In Denmark, the increased incidence can be explained partially by the increased use of antithrombotic agents. However, whether the increase also can be attributed to other commonly used agents, such as antidepressants, which are known to affect platelet function, is not yet clear, according to study background.
For this reason, Gaist and colleagues sought to provide subdural hematoma risk estimates associated with use of selective serotonin reuptake inhibitors. They additionally examined potential interactions associated with concomitant use of antidepressants, antithrombotic drugs and NSAIDs.
Researchers pooled data from various Danish registries on 10,885 patients (mean age, 69.5 years; 65% men) with subdural hematomas. Twenty-two percent of patients currently used antidepressants (15.7% selective serotonin reuptake inhibitors; 9.2% nonselective serotonin reuptake inhibitors). The analysis also included 435,379 birth year- and sex-matched controls from the general population.
Researchers calculated a 30-day mortality rate for patients with subdural hematoma of 15.9%. Compared with controls, cases had higher levels of comorbidity associated with high alcohol consumption (4.7% vs. 18.2%), stroke (7.1% vs. 17.5%), atrial fibrillation (8.5% vs. 17.9%), epilepsy (1.8% vs. 6.9%), dementia (2.8% vs. 6.1%), chronic renal failure (1.6% vs. 3.1%), chronic hepatic failure (1% vs. 2.7%) and coagulopathy (0.2% vs. 0.6%).
Current use of selective serotonin reuptake inhibitors (OR = 1.6; 95% CI, 1.5-1.71) and nonselective serotonin reuptake inhibitors (OR = 1.35; 95% CI, 1.25-1.47) appeared associated with an increased risk for subdural hematoma compared with nonuse of any antidepressant.
Researchers additionally observed an inverse association between subdural hematoma risk and duration of current use of either type of antidepressant. The risk appeared greatest with less than 1 month of use (selective serotonin reuptake inhibitors, OR = 2.55; 95% CI, 2.07-3.15; nonselective serotonin reuptake inhibitors, OR = 1.88; 95% CI, 1.46-2.41) compared with 3 or more years of antidepressant use (OR = 1.04; 95% CI, 0.93-1.17; OR = 1.12; 95% CI, 0.98-1.28).
Researchers observed similar risks for both low and high doses of antidepressants.
In analyses that assessed subdural hematoma risk associated with use of single or combined antidepressants, antithrombotic agents or NSAIDs, researchers found that combined use of antidepressants with antithrombotic agents or NSAIDs yielded similar ORs to those observed for single use of either agent.
However, the risk for subdural hematoma appeared greater among those who received antidepressants combined with vitamin K antagonists and NSAIDs (selective serotonin reuptake inhibitors, OR = 5.51; 95% CI, 2.7-11.22; nonselective serotonin reuptake inhibitors, OR = 6.81; 95% CI, 2.37-19.6).
A limitation of the study was that the data were observational and potentially subject to bias or residual confounding.
“Whether these reassuring findings extend to treatment of antidepressants with both an NSAID and an anticoagulant, in particular vitamin K antagonists, warrants further study,” the researchers wrote. – by Jennifer Southall
Disclosures: Gaist reports honoraria from AstraZeneca. Please see the study for all other authors’ relevant financial disclosures.
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