What is the Strongest NSAID?
There is no single "strongest" NSAID that consistently demonstrates superior analgesic efficacy across all pain conditions—ketorolac and indomethacin are among the most potent NSAIDs available, but no NSAID has been proven clinically superior to others in head-to-head comparisons for most pain conditions. 1, 2
Evidence on NSAID Comparative Efficacy
No Clear Winner Among NSAIDs
Multiple systematic reviews and guidelines consistently show no clear differences in pain relief between different NSAIDs for conditions including acute and chronic low back pain, postoperative pain, and cancer pain 1
The 2017 American College of Physicians systematic review found "no clear differences in pain relief between different NSAIDs for acute or chronic low back pain" across 21 trials for acute pain and 6 trials for chronic pain 1
A 2005 systematic review of total hip replacement found that various NSAIDs (ibuprofen, ketorolac, dexketoprofen, diclofenac, indomethacin, piroxicam) all demonstrated superior pain relief compared to placebo, but direct comparisons showed no significant differences between agents 1
Ketorolac: The Most Studied Potent NSAID
Ketorolac is notable as the only parenteral NSAID available in the US and has demonstrated analgesic efficacy comparable to standard doses of morphine and meperidine (pethidine) in postoperative settings 3, 4, 5
Ketorolac provides similar or superior analgesia to morphine, meperidine, or pentazocine in single-dose studies of postoperative pain and renal colic 4
In orthopedic surgery, 10 mg oral ketorolac demonstrated analgesic efficacy comparable to both 5 mg and 10 mg IM morphine 5
Ketorolac's analgesic effect may be slightly delayed compared to opioids but often persists longer 3
Indomethacin: Potent Prostaglandin Inhibition
Indomethacin is described as "a potent inhibitor of prostaglandin synthesis" and has been shown to be effective for long-term use in inflammatory conditions 6
Indomethacin demonstrates antipyretic and analgesic properties with therapeutic concentrations that have demonstrable effects in vivo 6
Clinical Decision-Making Algorithm
When Selecting an NSAID:
For acute severe pain requiring parenteral administration: Consider ketorolac (the only parenteral NSAID option in the US), which provides morphine-equivalent analgesia 3, 4
For inflammatory conditions: Any traditional NSAID is appropriate; indomethacin has particularly potent anti-inflammatory effects but no proven superiority over other NSAIDs 6, 2
For general pain management: The American College of Physicians recommends NSAIDs as first-line therapy without preference for a specific agent, as efficacy differences are not clinically significant 1, 7
Base selection primarily on safety profile and patient-specific risk factors rather than perceived potency differences 1, 2
Important Safety Considerations
Risk Stratification is More Important Than Potency
COX-2 selective inhibitors have lower risk for gastrointestinal adverse effects compared to nonselective NSAIDs (RR 0.83,95% CI 0.70-0.99) 1
Patients at high risk for GI toxicity include those aged >60 years, with history of peptic ulcer disease, significant alcohol use, or receiving corticosteroids/anticoagulants 1
Cardiovascular and renal risk factors must be assessed before prescribing any NSAID 7
The lowest effective dose should be used for the shortest necessary duration 7, 8
Ketorolac-Specific Warnings
The risk of serious gastrointestinal or operative site bleeding with ketorolac increases markedly when high dosages are used for more than 5 days, especially in elderly patients 3
Ketorolac should be limited to short-term use (≤5 days) due to increased risk of serious adverse events with prolonged therapy 3
Practical Recommendations
For most clinical scenarios, ibuprofen or naproxen are appropriate first-line choices due to extensive safety data, availability, and proven efficacy 7, 8
Recommended ibuprofen dosage is 400 mg up to a daily maximum of 3200 mg 7
If two NSAIDs are tried in succession without efficacy, use another approach to analgesia rather than continuing to trial different NSAIDs 1
Consider adding a proton pump inhibitor for patients at high risk of gastrointestinal complications 7
Monitor blood pressure, renal function (BUN, creatinine), liver function studies, CBC, and fecal occult blood every 3 months during chronic NSAID therapy 1