Risk of Intracranial Hemorrhage With Concomitant Use of Antidepressants and Nonsteroidal Anti-inflammatory Drugs: A Nested Case-Control Study

Abstract

Background Whereas previous studies found that concomitant antidepressant and nonsteroidal anti-inflammatory drug (NSAIDs) use may increase the risk of gastrointestinal bleeding, either drug alone increases the risk of intracranial hemorrhage (ICH). Objective To assess the risk for ICH in patients on concomitant treatment with antidepressants and NSAIDs. Methods This was a nested case-control study using national insurance claims data in Taiwan between 2005 and 2013. Drug exposure was measured and compared during 3 time windows: 1 to 30, 31 to 60, and 61 to 90 days before the index date, which is the date of the ICH event. Both traditional and newer-generation antidepressants were considered in this study. Results Patients exposed to both antidepressants and NSAIDs 1 to 30 days before the index date presented a 50% increased odds of developing ICH (OR: 1.53; 95% CI: 1.31-1.80) compared with patients receiving antidepressants alone. Specifically, the concomitant use of nonselective NSAIDs and antidepressants increased these odds compared with antidepressants alone (OR: 1.56; 95% CI: 1.31-1.84), but using a selective cyclooxygenase-2 inhibitor with antidepressant did not alter ICH risk. Regarding antidepressant class, newer-generation antidepressants generally increase the odds of developing ICH by 60% when used concomitantly with NSAIDs. Conclusion and Relevance Our results suggested that the concomitant use of antidepressants and NSAIDs was associated with an increased odds of developing ICH. NSAIDs, especially nonselective NSAIDs, and serotonergic antidepressants played an important role in this risk. Given the prevalent use of these 2 classes of drugs, this potential drug interaction deserves more attention.

Inverse association of anti-inflammatory prescription fills and suicide-related mortality in young adults: Evidence from a nationwide study of Swedish regions, 2006–2021

“…Given that combination treatment with NSAIDs and antidepressants is known to elevate risk of bleeding, which is a side effect exacerbated considerably by combination treatment with antidepressants ( Masclee et al, 2014 ), the question of the comparable efficacy of non-selective vs. selective NSAIDs in a psychiatric context is not trivial. Large sample studies, albeit in populations substantially older than the present one, have demonstrated increased risk of intracranial haemorrhage (ICH) during the first 30 days of combined use of antidepressants and NSAIDs ( Shin et al, 2015 ; Hou et al, 2021 ), a risk that has been indicated to be stronger in the case of non-selective agents ( Hou et al, 2021 ). As aforementioned, limitations of previous research evaluating the effects of antidepressant treatment and NSAIDs have not allowed for thorough investigation of long-term adverse consequences – although reporting combination treatment as relatively safe ( Köhler et al, 2014 ; Husain et al, 2017 ).…”

Das Blutungsrisiko unter Antidepressiva verstehen und einschätzen

“…Neben den Daten zu GI-Blutungen liegen zwei größere Originalarbeiten vor, die das Risiko für Hirnblutungen unter Personen, die mit einer Kombination von Antidepressiva mit NSAR im Vergleich zu denjenigen, die nur mit einem Antidepressivum behandelt wurden, untersucht haben [53,54]. In diesen Arbeiten war das Risiko für hämorrhagische Schlaganfälle innerhalb der ersten 30 Tage nach Beginn der Kombinationsbehandlung mit einem Antidepressivum 1,53 (95 % KI 1,31-1,80) [53] bzw. 1,60fach (95 % KI 1,32-1,85) erhöht gegenüber Personen, die nur mit einem Antidepressivum behandelt wurden.…”

Drug-induced intracerebral hemorrhage

“…Кроме того, риск ВМК увеличивался на фоне применения индометацина и НПВС в целом. Риск внутричерепных кровоизлияний увеличивается при одновременном применении неселективных НПВС с СИОЗС [45], трициклическими антидепрессантами [46].…”

“…Терапия НПВС. Фактором риска при применении данных препаратов является их совместное использование с другими препаратами -индукторами ВМК, например СИОЗС [45].…”