What are the next steps for treating osteoarthritis of the knee when Volteran (diclofenac) cream and Tylenol (acetaminophen) are not effective?

Next Steps for Knee Osteoarthritis When Topical Diclofenac and Acetaminophen Fail

Switch to oral NSAIDs as the next pharmacologic step, specifically oral diclofenac or naproxen, as these demonstrate superior efficacy to acetaminophen and topical agents for moderate knee osteoarthritis pain. 1

Immediate Pharmacologic Options

Oral NSAIDs (First-Line After Failed Topicals)

• Oral NSAIDs are strongly recommended for knee osteoarthritis when topical NSAIDs and acetaminophen prove inadequate 1
• Oral diclofenac or naproxen provide clinically and statistically significant pain relief and functional improvement compared to acetaminophen, which shows minimal efficacy beyond placebo in rigorous trials 2
• The 2020 VA/DoD guidelines give a weak recommendation for oral NSAIDs, acknowledging their effectiveness while noting cardiovascular and gastrointestinal risks that require monitoring 1
• Consider selective COX-2 inhibitors if the patient has elevated gastrointestinal risk, though cardiovascular risks remain 1

Intra-articular Corticosteroid Injection

• Strongly consider intra-articular corticosteroid injection for persistent knee pain, particularly if there is clinical effusion or signs of inflammation 1
• The 2020 VA/DoD guidelines suggest offering this "for patients with persistent pain due to osteoarthritis of the knee inadequately relieved by other interventions" 1
• Benefits typically last approximately 3 months, making this useful for acute exacerbations or as a bridge to other therapies 1
• The 2019 ACR/AF guidelines give a strong recommendation for intra-articular glucocorticoid injections in knee OA 1

Alternative Pharmacologic Agents

Duloxetine

• Offer duloxetine as an alternative or adjunctive therapy when NSAIDs are contraindicated, ineffective, or poorly tolerated 1
• The 2020 VA/DoD guidelines specifically recommend duloxetine for patients with "inadequate response or contraindications to acetaminophen or nonsteroidal anti-inflammatory drugs" 1
• This represents a conditional recommendation but provides a non-NSAID option for pain management 1

Topical Capsaicin

• Consider topical capsaicin as an adjunctive treatment, though evidence is weaker than for NSAIDs 1
• The 2020 VA/DoD guidelines suggest offering capsaicin for knee OA pain 1
• The 2019 ACR/AF guidelines give a conditional recommendation for topical capsaicin 1

Tramadol (Use With Extreme Caution)

• Tramadol receives only a conditional recommendation and should be reserved for patients who cannot tolerate NSAIDs and have failed other options 1
• The 2020 VA/DoD guidelines suggest against initiating opioids (including tramadol) for knee OA due to adverse effects without consistent benefit 1
• If considering tramadol, use the lowest effective dose for the shortest duration possible 3

Essential Non-Pharmacologic Interventions (Must Implement Concurrently)

Exercise and Physical Therapy

• Strongly recommend initiating or intensifying a structured exercise program, as this has the strongest evidence for long-term benefit 1
• The 2019 ACR/AF guidelines give a strong recommendation for regular, ongoing exercise programs 1
• Quadriceps strengthening and range-of-motion exercises are particularly effective 1
• Physical therapy should be part of the comprehensive management plan 1

Weight Loss (If Applicable)

• Mandate weight loss counseling for overweight or obese patients, as this provides sustained pain relief and functional improvement 1
• The 2019 ACR/AF guidelines give a strong recommendation for weight loss in overweight/obese patients with knee OA 1
• Combine diet and exercise approaches for optimal results 1

Assistive Devices

• Recommend tibiofemoral bracing for appropriate candidates, which receives a strong recommendation from the 2019 ACR/AF guidelines 1
• Consider cane use for unloading the affected knee, also strongly recommended 1

What NOT to Do

Avoid Routine Use of:

• Intra-articular hyaluronic acid: The 2022 AAOS guidelines recommend against routine use due to inconsistent evidence, though a subset of patients may benefit 1
• Opioids other than tramadol: The 2020 VA/DoD guidelines suggest against initiating opioids for knee OA 1
• Arthroscopic lavage/debridement: Not indicated unless there is true mechanical locking 4

When to Refer to Orthopedic Surgery

Consider orthopedic referral when the patient has:

• Exhausted appropriate conservative treatments including physical therapy, oral NSAIDs, and intra-articular injections 4
• Persistent pain with functional disability despite maximal medical management 4
• Radiographic evidence of significant joint deterioration 1
• Symptoms that substantially impair quality of life and activities of daily living 4

Key Information for Referral Letter:

• Document duration and response to physical therapy 4
• List all pharmacologic trials with dosing and efficacy 4
• Note whether intra-articular corticosteroid injections were offered or tried 4
• Describe functional impairment and impact on quality of life 4
• Include relevant comorbidities affecting surgical planning 4

Critical Pitfalls to Avoid

• Do not continue acetaminophen monotherapy if it has already failed—evidence shows minimal efficacy beyond placebo in moderate-to-severe knee OA 2
• Do not prescribe oral NSAIDs without assessing cardiovascular and gastrointestinal risk factors, as these medications carry FDA black box warnings 1, 5
• Do not delay non-pharmacologic interventions while escalating medications—exercise and weight loss have the most durable long-term benefits 1
• Do not refer for surgery prematurely without documenting adequate trials of conservative management 4