What is the best prescription medication to treat osteoarthritis of the knees?

Best Prescription Medication for Knee Osteoarthritis

Topical diclofenac is the best prescription medication for treating osteoarthritis of the knees due to its effectiveness in pain reduction with significantly fewer systemic side effects compared to oral NSAIDs. 1, 2

First-Line Treatment Options

Topical NSAIDs

• Topical diclofenac is highly effective for knee osteoarthritis pain with a positive effect size of 0.91 compared to placebo 1
• Available in various formulations including gel, patch, and solution with twice daily application providing significant pain relief 3
• Penetrates directly into the affected joint, with measurable concentrations in synovial tissue and fluid, providing targeted therapy 4
• Causes markedly fewer gastrointestinal adverse events compared to oral NSAIDs, with the main side effects being local application site reactions 1, 2
• Particularly beneficial for patients with increased gastrointestinal risk (age ≥60 years, history of peptic ulcer disease, concurrent use of corticosteroids or anticoagulants) 1

Oral NSAIDs

• Recommended for patients unresponsive to topical treatments, especially those with joint effusion 1
• For osteoarthritis, the recommended dosage of oral diclofenac is 100-150 mg/day in divided doses (50 mg twice or three times daily) 5
• More efficacious than acetaminophen but associated with increased gastrointestinal side effects 1
• Should be used at the lowest effective dose for the shortest duration to minimize adverse effects 5

Second-Line Treatment Options

Intra-articular Injections

• Intra-articular corticosteroid injections are indicated for acute exacerbations of knee pain, especially if accompanied by effusion 1
• Provide short-term pain relief (effective for 1-3 weeks) with effect size of 1.27 compared to placebo 1
• More effective in patients with joint effusion 1

Duloxetine

• FDA-approved for chronic musculoskeletal pain including osteoarthritis 6
• Clinical trials show significant pain reduction compared to placebo in knee osteoarthritis 6
• Provides an alternative mechanism of action for patients who cannot tolerate or have contraindications to NSAIDs 6

Treatment Algorithm

1. Initial Assessment:

   • Evaluate pain severity, functional limitations, and presence of inflammation/effusion 1
   • Consider patient's age, comorbidities, and risk factors for medication side effects 1

2. First-Line Treatment:

   • Start with topical diclofenac (available as 2% solution applied twice daily or 1% gel) 1, 3
   • For patients with minimal response to topical therapy after 2-4 weeks, consider:
     • Adding oral NSAIDs if no contraindications exist 1
     • Using intra-articular corticosteroid injection if effusion is present 1

3. Second-Line Treatment:

   • For patients with inadequate response to first-line treatments:
     • Consider duloxetine, especially in patients with contraindications to NSAIDs 6
     • Consider referral for physical therapy which has shown benefit in combination with pharmacological treatment 1

Important Considerations and Pitfalls

• Avoid long-term opioid therapy (including tramadol) for knee osteoarthritis pain as recommended by the VA/DoD Clinical Practice Guideline 1
• Monitor for adverse effects: Regular assessment of renal function, blood pressure, and gastrointestinal symptoms in patients using oral NSAIDs 1
• Consider age-related risks: Older patients (≥65 years) are at higher risk for NSAID-related complications, making topical formulations particularly valuable in this population 7
• Combination therapy: Optimal management often requires combining pharmacological treatments with non-pharmacological modalities such as exercise, weight reduction, and appropriate footwear 1
• Treatment expectations: Set realistic expectations regarding pain relief, as most treatments provide moderate rather than complete pain relief 8

Systematic reviews have consistently shown that diclofenac remains as effective as newer pain medications for osteoarthritis, providing a reliable benchmark for treatment 8.