What are alternative treatments to topical diclofenac (nonsteroidal anti-inflammatory drug (NSAID)) for an adult patient with a history of joint pain or inflammation, such as osteoarthritis?

Alternatives to Topical Diclofenac for Joint Pain

The best alternative to topical diclofenac is topical ketoprofen gel, which has demonstrated comparable efficacy with similarly favorable safety profiles in osteoarthritis, particularly for knee and hand pain. 1, 2

First-Line Topical Alternatives

Topical Ketoprofen

• Topical ketoprofen gel is the most evidence-based alternative, showing 72% response rates versus 33% with placebo in acute musculoskeletal pain (NNT 2.5), and 63% versus 48% with placebo in chronic osteoarthritis over 6-12 weeks (NNT 6.9). 2
• Ketoprofen provides similar pain relief magnitude to topical diclofenac with minimal systemic absorption, avoiding gastrointestinal, cardiovascular, and renal toxicity. 2, 3
• EULAR guidelines support topical NSAIDs as first-line pharmacological treatment, and ketoprofen is specifically validated as an effective alternative formulation. 1

Topical Capsaicin

• Topical capsaicin is a second-line topical option when NSAIDs are contraindicated or ineffective, though it requires 2-4 weeks of continuous use to achieve benefit. 1, 4
• High-concentration capsaicin (8%) showed moderate efficacy in postherpetic neuralgia (33% capsaicin vs 24% placebo, NNT 11), but evidence for osteoarthritis is less robust. 2, 5
• Critical caveat: Capsaicin causes frequent burning and stinging sensations (63% local adverse events versus placebo), which limits tolerability and may compromise blinding in trials, potentially inflating efficacy estimates. 1, 2, 5
• Low-concentration capsaicin (0.025-0.075%) has very low-quality evidence and higher withdrawal rates (15% vs 3% placebo, NNH 8). 2

Oral Pharmacological Alternatives

Acetaminophen (Paracetamol)

• Acetaminophen should be considered before oral NSAIDs, using regular dosing up to 4000 mg daily (consider maximum 3000 mg daily in elderly patients for enhanced safety). 1, 6
• NICE guidelines recommend acetaminophen and/or topical NSAIDs before oral NSAIDs, COX-2 inhibitors, and opioids. 1
• Important limitation: Acetaminophen has only weak efficacy at therapeutic doses and patients' experiences are variable. 1, 3

Oral NSAIDs or COX-2 Inhibitors

• Only prescribe oral NSAIDs when topical treatments have failed, using the lowest effective dose for the shortest possible duration (preferably on-demand). 1
• Always co-prescribe a proton pump inhibitor alongside any oral NSAID or COX-2 inhibitor for gastroprotection, choosing the one with lowest acquisition cost. 1, 6
• Oral NSAIDs effectively improve pain and function after 2-4 weeks, but carry substantial risks of gastrointestinal bleeding, cardiovascular events, renal insufficiency, and hepatotoxicity, particularly in elderly patients with comorbidities. 1, 7, 3
• Carefully assess cardiovascular, gastrointestinal, renal, and hepatic risk factors before prescribing, with particular caution in patients ≥65 years, those with hypertension, diabetes, or cardiovascular disease. 1

Non-Pharmacological Core Treatments

These must accompany any pharmacological management and should never be omitted:

• Strengthening exercises and low-impact aerobic fitness training are essential core therapy for all osteoarthritis patients. 1, 6
• Weight loss interventions if BMI ≥25 kg/m², as this reduces joint load and pain. 1, 8
• Local heat or cold applications may provide symptomatic relief, though evidence is weak and conflicting. 1
• Orthoses for hand osteoarthritis (particularly custom-made thermoplast or neoprene for thumb base OA) should be worn for at least 3 months to show benefit on pain and function. 1
• Patient education and self-management programs to counter misconceptions that osteoarthritis is inevitably progressive. 8, 6

Interventional Options

Intra-articular Corticosteroid Injections

• Consider intra-articular corticosteroid injections for moderate to severe pain when topical and oral analgesics provide insufficient relief. 1
• These are positioned as third-line therapy after topical NSAIDs and acetaminophen have been tried. 1

Treatments NOT Recommended

Avoid these interventions due to lack of efficacy evidence:

• Glucosamine and chondroitin products are not recommended due to lack of clinically important outcomes compared to placebo. 1, 8, 6
• Hyaluronic acid injections are not recommended. 8
• Rubefacients (topical salicylates) are not recommended for osteoarthritis. 1
• Electroacupuncture should not be used; insufficient evidence exists for acupuncture despite RCTs. 1, 8

Critical Safety Considerations

• Topical NSAIDs (including ketoprofen) have systemic adverse event rates (4.3%) no greater than placebo (4.6%) in acute pain, representing a major safety advantage over oral NSAIDs. 2
• Local adverse events with topical ketoprofen in chronic pain showed no increase over placebo (moderate-quality evidence). 2
• Common pitfall: Never exceed 4000 mg daily of acetaminophen to prevent hepatotoxicity, with strong consideration for 3000 mg limits in elderly patients. 6, 3
• Common pitfall: Avoid prolonged oral NSAID use at high doses, particularly in elderly patients who face substantially higher risks of serious adverse events. 1, 6, 3