Yes, gabapentin and nortriptyline can and should be used together for neuropathic pain
The combination of gabapentin and nortriptyline is superior to either medication alone for neuropathic pain, including post-herpetic conditions, and is explicitly recommended by clinical guidelines. 1
Evidence for Combination Therapy
The combination approach is well-supported:
A landmark randomized controlled trial demonstrated that gabapentin plus nortriptyline reduced pain scores significantly more than either drug alone (combination: 2.3/10 vs gabapentin alone: 3.2/10 vs nortriptyline alone: 2.9/10) in patients with diabetic polyneuropathy and postherpetic neuralgia 2
Mayo Clinic guidelines specifically state that "the combination of nortriptyline and gabapentin was superior to either of these 2 medications administered alone" 1
The synergistic effect has been confirmed in multiple preclinical studies with interaction indices of 0.134-0.348, indicating true synergy rather than just additive effects 3, 4
Mechanism and Rationale
This combination makes pharmacological sense because:
- The medications act on different neurotransmitter systems and pain pathways
- Gabapentin modulates voltage-gated calcium channels
- Nortriptyline (a tricyclic antidepressant) inhibits norepinephrine and serotonin reuptake
- Lower doses of each medication can be used in combination, potentially reducing side effects while maintaining efficacy 1
Specific Application to Your Patient
For a 71-year-old with persistent left-ear itching after facial shingles:
- This represents post-herpetic neuropathic symptoms (possibly post-herpetic itch, which shares mechanisms with post-herpetic neuralgia) 5, 6
- Gabapentin has documented efficacy for post-herpetic itch 5
- First-line treatment for post-herpetic complications includes gabapentinoids, tricyclic antidepressants (particularly nortriptyline), and their combination 7, 8, 9
Dosing Approach
Start conservatively in this elderly patient:
Gabapentin:
- Start 300 mg once daily at bedtime
- Titrate to 300 mg three times daily over 3 days
- Target maintenance: 300-600 mg three times daily (maximum 1800-3600 mg/day) 10
- Critical: Adjust for renal function - elderly patients have decreased creatinine clearance requiring dose reduction 10
Nortriptyline:
- Start 10-25 mg at bedtime
- Titrate slowly by 10-25 mg increments weekly
- Target: 50-75 mg at bedtime (lower than typical doses due to combination effect)
Safety Considerations
Important caveats for this 71-year-old patient:
- Renal function assessment is mandatory before starting gabapentin - dose must be adjusted based on creatinine clearance 10
- Nortriptyline has anticholinergic effects (dry mouth, constipation, urinary retention) - use cautiously in elderly
- Both medications cause sedation and dizziness - warn about fall risk 10
- The most common side effect in combination is dry mouth, which was significantly more frequent than gabapentin alone 2
- Start low, go slow with titration in elderly patients 11
When to Use Combination
Use combination therapy when:
- Either medication alone provides partial but insufficient relief
- Patient seeks additional pain relief beyond monotherapy
- You want to minimize doses of each individual agent 1, 2
The clinical guideline explicitly recommends: "use of this combination in patients who show a partial response to either drug given alone and seek additional pain relief" 2
Monitoring
- Assess pain/itch intensity at 1-2 week intervals
- Monitor for sedation, dizziness, and falls
- Check for anticholinergic side effects (dry mouth, constipation, confusion)
- Reassess renal function periodically given age