What is the next best step in management for a patient with neuropathic pain (burning and tingling) in their upper extremities who has not responded to Lyrica (pregabalin)?

Management of Neuropathic Pain After Pregabalin Failure

For a patient with burning and tingling in the upper extremities who has not responded to Lyrica (pregabalin), the next best step in management is to try a serotonin-norepinephrine reuptake inhibitor (SNRI) such as duloxetine or venlafaxine. 1

Alternative Pharmacological Options

When pregabalin fails to provide adequate relief for neuropathic pain, several evidence-based alternatives should be considered:

• Serotonin-norepinephrine reuptake inhibitors (SNRIs): Duloxetine (60mg daily) or venlafaxine (150-225mg daily) are recommended as the next step when pregabalin is ineffective 1

  • Duloxetine has shown consistent efficacy in peripheral neuropathic pain with effectiveness sustained for up to 1 year 1
  • Start with duloxetine 30mg once daily for 1 week before increasing to 60mg daily to reduce nausea 1
  • Venlafaxine typically requires 2-4 weeks to titrate to an efficacious dosage (150-225mg/day) 1

• Tricyclic antidepressants (TCAs): Consider a secondary-amine TCA such as nortriptyline or desipramine if SNRIs are contraindicated or ineffective 1

  • Start with low doses at bedtime and slowly titrate up 1
  • Monitor for anticholinergic side effects (dry mouth, orthostatic hypotension, constipation) 1
  • Obtain ECG screening for patients over 40 years and limit dosages to less than 100mg/day when possible 1

• Topical treatments: For localized neuropathic pain in the upper extremities, consider topical options 1

  • Capsaicin 8% patch or cream can provide pain relief for up to 12 weeks with a single 30-minute application 1
  • Topical lidocaine can be used alone or in combination with other first-line therapies 1

Dose Considerations for Pregabalin

Before completely abandoning pregabalin, consider whether the dose was optimized:

• Many patients who do not respond to lower doses of pregabalin may respond when the dose is escalated 2
• Pregabalin can be titrated up to 600mg daily in divided doses if lower doses were ineffective 2, 3
• Higher doses of pregabalin have been shown to result in significantly greater pain reduction 2
• If the patient was not on the maximum dose, consider dose escalation before switching to alternative treatments 2, 4

Non-Pharmacological Approaches

Consider adding non-pharmacological interventions alongside medication changes:

• Hypnosis is recommended for neuropathic pain (strong recommendation, low-quality evidence) 1
• Physical and occupational therapy are recommended for chronic pain (strong recommendation, low-quality evidence) 1
• Cognitive behavioral therapy (CBT) is recommended for chronic pain management as it promotes adaptive behaviors while addressing maladaptive behaviors (strong recommendation, moderate-quality evidence) 1
• Acupuncture might be considered for chronic pain (weak recommendation, moderate-quality evidence) 1

Combination Therapy

If monotherapy with alternative agents provides inadequate relief, consider combination approaches:

• Combining an SNRI with topical treatments may provide better pain control 1
• Recent research suggests that combining medications with different mechanisms of action (such as voltage-gated sodium and calcium channel blockers) might provide better analgesia with fewer side effects 5
• For patients with severe, refractory pain, referral to a pain specialist or multidisciplinary pain center should be considered 1

Special Considerations

• Monitor for adverse effects: Common side effects of SNRIs include nausea (duloxetine) and potential blood pressure increases (venlafaxine) 1
• Reassess pain frequently: Evaluate pain reduction and quality of life improvements regularly to determine treatment efficacy 1, 6
• Treatment goals: Aim for at least 30% reduction in pain intensity (moderate benefit) or 50% reduction (substantial benefit) 3
• Alpha lipoic acid (ALA) may be considered for difficult-to-treat neuropathic pain, particularly in diabetic neuropathy 1

Treatment Algorithm

1. Verify pregabalin dosing was optimized (up to 600mg/day in divided doses) 2, 3
2. If optimized pregabalin failed, initiate SNRI (duloxetine 60mg daily or venlafaxine 150-225mg daily) 1
3. If inadequate response after 4-6 weeks, consider adding topical treatments or switching to a TCA 1
4. Incorporate appropriate non-pharmacological approaches throughout treatment 1
5. For refractory pain after trials of first-line medications alone and in combination, refer to a pain specialist 1