Which of the following best describes a potential interaction risk when combining an SSRI with NSAID therapy?

• A. Increased risk of bleeding
• B. Enhanced analgesic effect with reduced bleeding risk
• C. No interaction expected
• D. Reduced risk of gastrointestinal symptoms

Answer: (A)

The main concept is that this combination increases bleeding risk. SSRIs reduce platelet serotonin uptake, which weakens platelet aggregation and makes hemostasis less effective. NSAIDs inhibit COX enzymes, lowering thromboxane A2 and compromising the protective gastric mucosa, further increasing bleeding risk. Put together, they can produce more bleeding—especially GI bleeding—than either agent alone. In practice, be vigilant for signs of bleeding (bruising, tarry stools, unusual gum or nasal bleeding) and consider using the lowest effective NSAID dose, switching to a different analgesic like acetaminophen when possible, or adding protective strategies if NSAIDs must be used.