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Risk of serious upper gastrointestinal events with concurrent use of NSAIDs and SSRIs: a case-control study in the general population



To study the risk of serious upper gastrointestinal (GI) events associated with the concurrent use of selective serotonin re-uptake inhibitors (SSRIs) and different types of non-steroidal anti-inflammatory drugs (NSAIDs).


This was a nationwide, register-based matched case-control study on non-institutionalized residents of Finland during the period 2000–2004. Patient-cases with serious upper GI events (n = 9191) were drawn from the Hospital Discharge Register, and individually matched controls (n = 41,780) were drawn from the Population Register. Logistic regression was applied in the data analysis, and adjustments were made for various co-morbidities and the use of other drugs associated with the risk of serious upper GI event.


The adjusted odds ratio (AOR) of serious upper GI events for SSRI use compared to non-use of SSRIs or NSAIDs was 1.30 [95% confidence interval (95%CI: 1.13–1.50)], and the AOR for concurrent SSRI and NSAID use compared to the non-use of either drug was 4.19 (95%CI: 3.30–5.31). The AOR of upper GI events for the concurrent use of SSRIs with NSAIDs compared to patients using NSAIDs only was 1.57 (95%CI: 1.24–1.99). The respective AOR for traditional, non-selective NSAIDs was 1.77 (95%CI: 1.31–2.38), for semi-selective NSAIDs (nimesulide, nabumetone, meloxicam, and etodolac) 1.30 (95%CI: 0.76–2.24) and for COX-2 selective NSAIDs 1.33 (95%CI: 0.70–2.50).


The concurrent use of SSRIs and NSAIDs is associated with a moderate excess relative risk of a serious upper GI event when compared with NSAID use alone.

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We thank Hilkka Ruuska and Kristiina Tyrkkö, the Social Insurance Institution, for their data management skills.

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Correspondence to Arja Helin-Salmivaara.

Additional information

Financial disclosure: Timo Klaukka has been employed by the financier and organizer of the national sickness insurance scheme, including drug reimbursements. No other conflict of interests has been announced.

Funding: The Centre for Pharmacotherapy Development funded the statistical analysis. The funding source was not involved in the analysis.

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Helin-Salmivaara, A., Huttunen, T., Grönroos, J.M. et al. Risk of serious upper gastrointestinal events with concurrent use of NSAIDs and SSRIs: a case-control study in the general population. Eur J Clin Pharmacol 63, 403–408 (2007).

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  • Case-control study
  • COX-2 selective NSAIDs
  • NSAIDs
  • SSRIs
  • Upper gastrointestinal hemorrhage