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Nonsteroidal anti-inflammatory drugs (standard or coxibs) - prescribing issues - Management
What should I do for a person who requires a selective serotonin reuptake inhibitor and an NSAID?

  • The risk of upper gastrointestinal bleeding is increased when a selective serotonin reuptake inhibitor (or venlafaxine or duloxetine) and a nonsteroidal anti-inflammatory drug (NSAID) are concomitantly prescribed:
    • Therefore, advise people to seek urgent medical advice and to not take any more of the NSAID if a bleeding episode is experienced.
  • If an NSAID is considered necessary, weigh the risks and benefits and consider prescribing gastroprotection.
    • Consider prescribing mirtazapine or trazodone as alternative antidepressants.
Basis for recommendation

These recommendations are based on information in the British National Formulary [BNF 55, 2008] and NICE guidance Depression in adults with a chronic physical health problem [NICE, 2009]. They are supported by additional evidence from a recently-published meta-analysis of four observational studies involving 153,000 people [Loke et al, 2008]:

  • The meta-analysis found:
    • A significant risk of upper gastrointestinal (GI) bleeding after selective serotonin reuptake inhibitor (SSRI) use (odds ratio 2.36, 95% CI 1.44 to 3.85, p = 0.0006).
    • An even greater risk of upper GI bleeding after concomitant SSRI and NSAID use (odds ratio 6.33, 95% CI 3.40 to 11.8, p < 0.0001).
    • In people older than 50 years of age with no risk factors for upper GI bleeding:
      • For every 411 people treated with SSRIs, one person experienced upper GI bleeding (NNH = 411).
      • For every 106 people treated with an SSRI and an NSAID together, one person experienced upper GI bleeding (NNH = 106).
  • The investigators also analysed 101 spontaneous postmarketing reports of episodes of upper GI bleeding associated with SSRI use:
    • 67% of the reports were from people who were also using an NSAID.
    • The median time to upper GI bleeding was 25 weeks after starting SSRI treatment.
  • Venlafaxine and duloxetine also inhibit serotonin reuptake, so can be expected to interact similarly.

© NHS Institute for Innovation and Improvement