Topical NSAIDs come out on top for osteoarthritis and musculoskeletal pain, but not all guidelines reflect the evidence

Topical non-steroidal anti-inflammatory drugs (NSAIDs) are more effective than oral formulations, says clinical pharmacist Joyce McSwan, managing director of PainWise, who recently reviewed the evidence in a Healthed Talk.

The most effective NSAIDs seem to be gel formulations of diclofenac, ibuprofen and ketoprofen, and diclofenac patches (although the latter are not available in Australia), says McSwan, citing this 2016 Cochrane review and this 2021 review published in the British Medical Journal, both of which focused on NSAIDs for musculoskeletal pain.

This is especially relevant to osteoarthritis and acute soft tissue injuries, where McSwan says the evidence comes out clearly in favour of topicals.

Not only do the topical NSAIDs work better than their oral counterparts for these indications, but they are also less likely to cause gastrointestinal or cardiovascular side effects, due to their low absorption rates (generally in the order of 3 – 8%).

Oral NSAIDs do have some effect in low back pain and sciatica, but they require higher doses to make a difference in osteoarthritis.

“In the context of topical NSAIDs for osteoarthritis, the evidence is strong, which is why most international guidelines for OA put topicals as first line,” McSwan says.

However, not all guidelines have caught up.

For example, the RACGP guideline for osteoarthritis recommends NSAIDs for hip and knee osteoarthritis, but specifically makes a neutral recommendation for topical formulations, stating they can neither recommend nor discourage them.

However, this guideline hasn’t been updated since 2009, and McSwan is hopeful that will change.

Likewise, the NSW Agency for Clinical Innovation recommends NSAIDs for short term pain relief for acute low back pain if paracetamol alone is not effective—but the guideline does not differentiate between oral or topical formulations.

McSwan also notes that there is no additional benefit to combining topical and oral NSAIDs over either formulation alone. Further, risk of side effects increases when different NSAIDs are combined. Gastrointestinal adverse events are the most common.

“The inclusion of a PPI might have some benefit,” says McSwan, but this only protects the upper gut.

NSAIDs also increase the risk of myocardial infarction in patients with established cardiovascular disease. They can increase systolic blood pressure by up to 5 mmHg, and can also cause haemorrhagic stroke. They may also precipitate heart failure, especially in patients on diuretics.

“There is no safe non-steroidal treatment window that exists for patients with cardiovascular disease,” McSwan says.

The risk increases within a week of starting treatment, and increases further with longer use. It also seems to be dose dependent for most NSAIDs except diclofenac, which has similarly increased risk at any dose.

“Keep the dose low, and the treatment period as short as possible,” McSwan says.

NSAID facts

• Oral NSAIDs have some effect in low back pain and sciatica, but require higher doses to make a difference in osteoarthritis.
• The most effective NSAIDs seem to be gel formulations of diclofenac, ibuprofen and ketoprofen, and diclofenac patches (although the latter are not available in Australia).
• The systemic absorption of topical NSAIDs is low, so they do not increase the risk of gastrointestinal and cardiovascular side effects.
• Combining topical and oral NSAIDs does NOT offer additional benefit, and increases risk of side effects.
  Source: Clinical pharmacist Joyce McSwan.

Some newer over the counter options include ibuprofen as a lysine or sodium dihydrate these are more bioavailable and therefore act faster). Both ibuprofen and naproxen are now also available over the counter as slow release 12 or 24 hour formulations, she says.

To sum up, McSwan says it’s always a matter of weighing up risk vs benefit of the specific formulation, but all in all NSAIDs remain an effective analgesic option, often comparable to opioids with less side effects.