A drug from the class of antidepressants called selective serotonin reuptake inhibitors (SSRIs), such as Prozac, Zoloft or Paxil, added to a nonsteroidal anti-inflammatory drug (NSAID), such as Motrin, Aspirin or Celebrex, can interact to increase the risk of upper gastrointestinal bleeding, according to a report in current issue of Alimentary Pharmacology and Therapeutics.
"Before I did this study, I didn't worry at all when I saw patients who were on combination SSRIs and NSAIDs," Dr. Yoon K. Loke from the University of East Anglia, Norwich, UK told Reuters Health. "Now that I have seen the fairly substantial excess risk (beyond even what I had imagined beforehand), physicians should carefully review the patients' charts — do they need to be on these drugs (at all), or are there safer alternatives?"
Loke and colleagues conducted a review to investigate the risk of upper gastrointestinal hemorrhage with SSRIs and to evaluate the possibility of an interaction between SSRIs and NSAIDs contributing to such bleeding.
The researchers analyzed the findings of four studies containing 153,000 patients and found that those taking SSRIs alone had 2.4-times the risk of upper gastrointestinal hemorrhage and those taking NSAIDs alone had 3.2-times the risk. However, in patients taking both SSRIs and NSAIDs the risk of upper gastrointestinal hemorrhage was 6.3-times greater than normal.
Based on these findings, the investigators estimate that a patient would most likely develop a problem after taking an SSRI 318 times per year. However, for those taking both drugs, they would only need to take them 82 times before an adverse evident would occur, Lok's group predicts.
For those with other risk factors for gastrointestinal bleeding, the number would be even lower, the researchers estimate.
In postmarketing reports to regulatory agencies, the average time to occurrence of upper gastrointestinal hemorrhage was after 25 weeks of SSRI treatment, with 38 percent of the reported cases occurring in patients younger than 60 years.
"Fewer people might be harmed from drug overdose with SSRIs (than with tricyclic antidepressants), but this is very likely to be counterbalanced by an excess of admissions with GI bleeding (thus increasing the costs and workload of the health service, and reducing the cost-effectiveness of the drug)," Loke said.
If a patient had "depression and arthritis, (both of which are very common), alarm bells would now ring in my mind and I would think carefully about which drugs to use," Loke said. "The benefit-to-harm profile needs to be thoroughly considered, given the substantial risks of harm here."
SOURCE: Alimentary Pharmacology and Therapeutics, October 5, 2007.