Interaction between selective serotonin reuptake inhibitors and nonsteroidal antiinflammatory drugs: review of the literature.

OBJECTIVE: To evaluate the evidence of an interaction between selective serotonin reuptake inhibitors (SSRIs) and nonsteroidal antiinflammatory drugs (NSAIDs) producing an increased risk for gastrointestinal adverse outcomes such as bleeding.

METHODS: We searched MEDLINE for English-language literature published between 1966 and August 2005. All studies examining gastrointestinal adverse effects from an SSRI-NSAID combination were included.

DATA SYNTHESIS: Four retrospective studies examined gastrointestinal adverse outcomes from the combination of SSRIs and NSAIDs. The risk ratio for an upper gastrointestinal bleed from this drug combination (compared with not receiving either agent) ranged from 3.3-15.6, and the risk ratio for gastrointestinal adverse effects was 12.4. Two studies found that the risk for an upper gastrointestinal bleed from the drug combination exceeded the additive risk of the agents alone. The risk ratio for an upper gastrointestinal bleed from an SSRI-aspirin interaction was 1.9-7.2. In addition, the number needed to harm in terms of an upper gastrointestinal bleed from an SSRI-NSAID combination ranged from 62-75 patient-years, and the number needed to harm for gastrointestinal adverse effects was 2 patient-years.

CONCLUSION: Concurrent use of an SSRI and NSAID increases the risk of gastrointestinal adverse outcomes such as bleeding. Clinicians must take care to avoid these negative outcomes by altering NSAID or SSRI therapy, or by providing ulcer-protective drugs.