Why do Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) increase the risk of diverticulitis?

Why NSAIDs Increase Risk of Diverticulitis

NSAIDs increase the risk of diverticulitis primarily through their inhibition of prostaglandin synthesis, which compromises the protective mucosal barrier of the colon, impairs local immune responses, and may alter colonic motility—all of which facilitate bacterial invasion and inflammation of diverticula. 1

Mechanism of Increased Risk

Prostaglandin Inhibition and Mucosal Integrity

• NSAIDs block cyclooxygenase (COX) enzymes, reducing prostaglandin production throughout the gastrointestinal tract 1
• Prostaglandins are critical for maintaining the colonic mucosal barrier, promoting mucus secretion, and ensuring adequate mucosal blood flow 1
• When this protective barrier is compromised, the colonic mucosa becomes more vulnerable to bacterial translocation into diverticula, triggering inflammation 1

Impact on Immune Function

• Prostaglandins play essential roles in local immune regulation and inflammatory responses 1
• NSAID-induced suppression of these mediators may impair the colon's ability to contain localized bacterial invasion within diverticula 1
• This creates conditions favorable for progression from asymptomatic diverticulosis to acute diverticulitis 2

Differential Risk by NSAID Type

• Non-aspirin NSAIDs carry substantially higher risk than aspirin, with odds ratios of 1.72 for diverticulitis and 3.13 for complicated diverticulitis 1, 3, 4
• Aspirin shows a more modest association (relative risk 1.25-1.49), likely due to its different COX-1/COX-2 selectivity profile and lower doses used for cardiovascular protection 2, 4
• The risk appears dose-dependent, with regular use (≥2 times per week) showing the strongest associations 2

Clinical Evidence Supporting the Association

Magnitude of Risk

• Regular NSAID users have a 3.2-fold increased risk of developing diverticulitis compared to non-users 3
• For complicated diverticulitis specifically, the risk increases to 3.13-fold with NSAIDs 4
• One case-control study found that 48% of patients with severe diverticular complications were taking NSAIDs at admission, compared to only 18-20% of controls 5

Diverticular Bleeding Risk

• NSAIDs increase risk of diverticular bleeding even more dramatically, with odds ratios of 6.90 for non-aspirin NSAIDs 4
• Aspirin carries a 2.84-fold increased risk of diverticular bleeding 4
• Intermediate aspirin doses (2-5.9 tablets/week) and frequency (4-6 days/week) show the highest bleeding risk 2

Guideline-Based Recommendations

Primary Prevention Strategy

• The AGA strongly recommends advising patients with a history of diverticulitis to avoid non-aspirin NSAIDs when possible 1, 6
• Patients with recurrent episodes or complicated diverticular disease should be especially vigilant about NSAID avoidance 6, 7

Aspirin Exception for Cardiovascular Protection

• Low-dose aspirin prescribed for secondary cardiovascular prevention should generally NOT be discontinued in patients with prior diverticulitis 6, 8
• The protective effects of aspirin on all-cause mortality and myocardial infarction typically outweigh the modest increased diverticulitis risk 6, 8

Alternative Pain Management

• Acetaminophen should be the primary analgesic for patients with diverticular disease history 6, 7
• For severe pain requiring stronger analgesia, opioids are preferable to NSAIDs in this population 7
• When opioids are necessary, consider naloxegol for managing opioid-induced constipation without increasing intra-colonic pressure 7

Critical Clinical Pitfalls

COX-2 Inhibitors Are Not Safe Alternatives

• While COX-2 selective inhibitors (coxibs) reduce upper GI ulcer risk by approximately 50%, evidence for lower GI protection is limited 1
• Coxibs still carry cardiovascular risks and should not be considered "safe" alternatives in diverticular disease 1

Proton Pump Inhibitors Do Not Protect

• PPIs reduce upper GI bleeding risk but provide no protection against lower GI bleeding from diverticulosis 6
• Co-prescribing a PPI does not make NSAID use safe in patients with diverticular disease 6

Hidden NSAID Exposure

• Many patients use over-the-counter NSAIDs (ibuprofen, naproxen) without considering them "real medication" 6
• Combination cold/flu medications and some topical preparations contain NSAIDs with systemic absorption 6
• Provide written instructions listing specific medications to avoid by both brand and generic names 6

Polypharmacy Concerns

• Combining NSAIDs with aspirin dramatically increases GI risk to more than 10-fold 1
• Concomitant use of corticosteroids or anticoagulants further amplifies risk 1
• Opiate analgesics, like corticosteroids, are independently associated with diverticulitis and perforation 1