What is the next best medication for a patient with arthritis, spinal stenosis, and neuropathic pain who is already on maximum dose of pregabalin (lyrica)?

Next Best Medication for Neuropathic Pain on Maximum Pregabalin

Add duloxetine 30 mg once daily for one week, then increase to 60 mg once daily, as this is the guideline-recommended first-line agent to combine with pregabalin for inadequate pain control in neuropathic pain. 1

Rationale for Duloxetine as Next Step

Since this patient is already on maximum dose pregabalin with persistent pain (Step 3 of neuropathic pain management), the evidence-based approach is to add another first-line medication rather than switch 1. The patient previously could not tolerate duloxetine due to nausea, but this can be mitigated:

• Start duloxetine at 30 mg once daily for 1 week before increasing to 60 mg once daily - this dosing strategy specifically reduces nausea, which is the most common adverse effect 1
• Duloxetine has proven efficacy in painful diabetic neuropathy with sustained effectiveness for 1 year, and importantly does not cause clinically significant electrocardiographic or blood pressure changes 1
• The combination of pregabalin plus duloxetine targets different mechanisms (calcium channel modulation plus serotonin-norepinephrine reuptake inhibition) for synergistic effect 1

Alternative if Duloxetine Still Not Tolerated

If nausea persists despite the gradual titration strategy, consider a secondary amine tricyclic antidepressant (nortriptyline or desipramine) starting at 10 mg daily in this elderly patient 1, 2:

• Maximum dose should not exceed 75 mg/day in elderly patients, especially those >75 years 2
• Secondary amines (nortriptyline, desipramine) are better tolerated than tertiary amines (amitriptyline) with fewer anticholinergic effects 1
• Obtain screening ECG before starting, as cardiac toxicity is a concern - limit dosages to <100 mg/day and use caution given this patient's falls and potential cardiac comorbidities 1
• Allow 6-8 weeks for adequate trial, including 2 weeks at highest tolerated dose 1

Critical Safety Considerations for This Patient

This patient's frequent falls (3-4 times, legs "going stiff") and sleep apnea require heightened vigilance when adding any CNS-active medication:

• Monitor closely for increased sedation, dizziness, and cognitive effects with combined pregabalin-duloxetine therapy 2
• The patient's absence seizures on lamotrigine, memory issues, and falling asleep inappropriately (on toilet) suggest significant CNS vulnerability 2
• Duloxetine has advantage over TCAs in not causing orthostatic hypotension, which is crucial given the fall risk 1

Topical Adjunct Option

Consider adding lidocaine 5% patch to localized areas of pain (right knee, fingers) as this can be used safely in combination with systemic agents 1, 2:

• Minimal systemic absorption makes it particularly safe in elderly patients with multiple comorbidities 1, 2
• Can be applied daily to painful sites without drug-drug interactions 1

Timeline and Monitoring

• Reassess pain and quality of life after 2-4 weeks of duloxetine at target dose (60 mg daily) 2
• Treatment is successful if pain reduced by ≥30% from baseline 2
• If inadequate response after 4 weeks at maximum tolerated dose, consider referral to pain specialist as outlined in Step 4 of neuropathic pain management 1
• The patient already has pain clinic appointment scheduled for December - this timing allows trial of duloxetine before specialist review 1

What to Avoid

Do not add gabapentin - it has the same mechanism as pregabalin (calcium channel α2-δ ligand) and provides no additional benefit 1

Avoid opioids at this stage - they are reserved for acute neuropathic pain, cancer pain, or when first-line medications fail, and would significantly increase fall risk in this patient 1