What are the acceptable doses of gabapentin (Neurontin) and duloxetine (Cymbalta) that can be combined to treat neuropathy?

Acceptable Doses of Gabapentin and Duloxetine for Neuropathic Pain Treatment

For neuropathic pain treatment, gabapentin can be combined with duloxetine at doses of gabapentin 900-3600 mg/day (divided into 3 doses) and duloxetine 60-120 mg/day. 1

Gabapentin Dosing

Initial Titration

• Day 1: 300 mg at bedtime
• Day 2: 300 mg twice daily
• Day 3: 300 mg three times daily (900 mg/day) 1

Maintenance Dosing

• Effective dose range: 900-3600 mg/day in divided doses
• Most patients achieve adequate pain relief at 1800 mg/day 1
• Maximum time between doses should not exceed 12 hours 1
• Dose adjustment required for renal insufficiency 2

Duloxetine Dosing

Initial Titration

• Start with 30 mg daily for one week 1
• Increase to 60 mg daily 2

Maintenance Dosing

• Effective dose range: 60-120 mg daily 1
• Analgesic effect occurs at lower doses than required for depression 2
• Contraindicated in hepatic disease 2

Combination Therapy Considerations

The combination of gabapentin and duloxetine provides complementary mechanisms of action:

• Gabapentin acts on α-δ calcium channels 2
• Duloxetine works through serotonin and norepinephrine reuptake inhibition 3

When combining these medications:

1. Start with lower doses of each medication
2. Titrate one medication to an effective dose before adding the second
3. Monitor for overlapping side effects, particularly:
   • Somnolence
   • Dizziness
   • Weight gain 1

Evidence for Efficacy

• Gabapentin at 1200 mg or higher provides substantial pain relief (≥50% reduction) in 38% of diabetic neuropathy patients compared to 21% with placebo (NNT 5.9) 4
• Duloxetine at 60 mg daily is effective for diabetic neuropathy with a risk ratio for 50% pain reduction of 1.73 (NNT 5) 3
• Combination therapy may provide superior efficacy compared to either medication alone 2

Monitoring and Adverse Effects

Common Adverse Effects

• Gabapentin: dizziness (19%), somnolence (14%), peripheral edema (7%), gait disturbance (14%) 4
• Duloxetine: nausea, somnolence, dizziness, dry mouth 3

Monitoring

• Assess pain control, function, and adverse effects regularly
• Watch for increased side effects when using both medications
• Approximately 16% of patients discontinue gabapentin due to side effects 4
• Serious adverse events are rare with both medications 3, 4

Special Considerations

• Avoid abrupt discontinuation of either medication; taper over at least one week 1
• Inform patients that therapeutic effects may take several days to weeks to develop 1
• Consistent dosing is required for gabapentin; it is not effective as PRN medication 1
• Consider comorbid depression when selecting medications 1
• Elderly patients require lower starting doses and slower titration 1

By following these dosing guidelines and monitoring for adverse effects, the combination of gabapentin and duloxetine can effectively manage neuropathic pain with acceptable tolerability.