What are the adjuvant therapy options for chronic knee pain?

Adjuvant Therapy for Chronic Knee Pain

For chronic knee pain, particularly from osteoarthritis, duloxetine (60 mg daily) is the primary adjuvant pharmacologic therapy when first-line treatments (acetaminophen, NSAIDs, topical agents) provide inadequate relief, while acupuncture and transcutaneous electrical nerve stimulation (TENS) serve as conditional adjuvant options only for surgical candidates who cannot or will not undergo arthroplasty. 1

Pharmacologic Adjuvant Options

Duloxetine (Primary Adjuvant)

• Duloxetine is strongly recommended as adjunctive therapy for patients with inadequate response or contraindications to acetaminophen or NSAIDs 1
• Initiate at 30 mg daily and increase to goal dose of 60 mg daily 1
• Must be taken daily (not as-needed) and requires 2-4 week taper when discontinuing after more than 3 weeks of therapy 1
• Provides significant reductions in both pain and physical function improvements 1
• Works through selective serotonin and norepinephrine reuptake inhibition 1

Opioid Analgesics (Limited Role)

• The 2021 VA/DoD guidelines recommend against initiating opioids (including tramadol) for knee osteoarthritis pain due to limited benefit and high risk of adverse effects 1
• The 2012 ACR guidelines conditionally support opioids only for patients who have failed both nonpharmacologic and pharmacologic modalities AND are unwilling or unable to undergo total knee arthroplasty 1
• When used, must follow American Pain Society/American Academy of Pain Medicine recommendations for chronic non-cancer pain management 1
• This represents a significant shift in practice—newer evidence strongly disfavors opioid use compared to older guidelines 1

Intra-articular Corticosteroid Injections (Adjunctive)

• Recommended for persistent pain inadequately relieved by other interventions 1
• Particularly indicated for acute flares, especially when accompanied by joint effusion 2
• Should be avoided for 3 months preceding planned joint replacement surgery 1
• Provides shorter duration relief (weeks) compared to some other interventions 1

Non-Pharmacologic Adjuvant Options

Acupuncture (Highly Conditional)

• Conditionally recommended ONLY when patients have chronic moderate-to-severe pain AND are candidates for total knee arthroplasty but are unwilling to undergo the procedure or have contraindications to surgery 1
• This is a very narrow indication—not recommended as general adjuvant therapy 1
• The 2021 VA/DoD guidelines found insufficient evidence to recommend for or against acupuncture 1

Transcutaneous Electrical Nerve Stimulation (TENS)

• Same highly conditional recommendation as acupuncture—only for surgical candidates who cannot or will not undergo arthroplasty 1
• Insufficient evidence in 2021 guidelines to recommend for or against TENS 1

Physical Therapy (Core, Not Adjuvant)

• While technically adjuvant to medications, physical therapy should be considered foundational rather than supplementary 1
• Strongly recommended as part of comprehensive management, with evidence for sustained pain reduction and functional improvement for 2-6 months 2
• Can be delivered via individual sessions, group visits, internet-based, or telephone-based approaches without loss of effectiveness 1

Interventions NOT Recommended as Adjuvants

Hyaluronic Acid Injections

• Not mentioned in recent VA/DoD guidelines for knee OA 1
• Older evidence showed pain relief lasting months but offset by slower onset and requirement for 3-5 weekly injections 1
• No evidence for disease modification 1

Glucosamine and Chondroitin

• Conditionally NOT recommended due to lack of efficacy evidence 2

Topical Capsaicin

• Conditionally NOT recommended by ACR 2
• Some older guidelines suggested it for knee OA 1

Clinical Algorithm for Adjuvant Selection

Step 1: Ensure first-line therapies are optimized (acetaminophen up to 4000 mg/day, topical NSAIDs for knee, oral NSAIDs if not contraindicated) 1, 2

Step 2: If inadequate response, add duloxetine 30-60 mg daily as primary adjuvant 1

Step 3: Consider intra-articular corticosteroid injection for persistent pain or acute flares with effusion 1, 2

Step 4: If patient is surgical candidate but refuses or has contraindications, consider acupuncture or TENS 1

Step 5: If all conservative measures fail, refer for surgical consultation 1

Critical Pitfalls to Avoid

• Do not initiate opioids as adjuvant therapy—this represents outdated practice with current evidence showing limited benefit and significant harm 1
• Do not use acupuncture or TENS broadly—these are only for the very specific population of surgical candidates who cannot undergo surgery 1
• Do not forget to taper duloxetine properly—abrupt discontinuation after >3 weeks can cause withdrawal symptoms 1
• Avoid corticosteroid injections within 3 months of planned arthroplasty 1