Alternative Non-Narcotic Medications for Neuropathic Pain When Gabapentin is Intolerable
If gabapentin is intolerable, pregabalin, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), capsaicin, or alpha lipoic acid should be considered as alternative non-narcotic medications for neuropathic pain management. 1, 2
First-Line Alternatives
Pregabalin
- Dosing: Start at 75mg twice daily, titrate to 300-600 mg/day divided in 2-3 doses 2
- Advantages over gabapentin:
- Higher bioavailability (>90%, dose-independent)
- Faster titration (days vs weeks)
- Lower therapeutic dose (150-600 mg/day vs 900-3600 mg/day)
- Fewer daily doses (2-3 times vs 3 times) 2
- Efficacy: FDA and EMA approved for neuropathic pain with NNT of 4.04 for 600 mg/day 2
- Side effects: Similar to gabapentin - dizziness (20.9%), somnolence (35.7%), peripheral edema (10.4%), weight gain 3
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
- Options: Duloxetine (60-120 mg/day) or Venlafaxine (150-225 mg/day) 1
- Advantages:
- Additional antidepressant effects
- Once-daily dosing for duloxetine
- FDA approved for diabetic neuropathy (duloxetine) 1
Tricyclic Antidepressants (TCAs)
- Options: Amitriptyline (25-75 mg/day) or Imipramine (25-75 mg/day) 1
- Efficacy: NNT of 1.5-3.5 when carefully titrated 1
- Caution:
- Start at low dose (10 mg/day), especially in older patients
- Avoid in patients with cardiovascular disease
- Monitor for anticholinergic side effects
- Increased risk of sudden cardiac death at doses >100 mg/day 1
Topical Options
Capsaicin
- Application: 8% dermal patch or cream at the site of pain 1
- Efficacy: A single 30-minute application can provide pain relief for at least 12 weeks 1
- Administration tip: Apply 4% lidocaine for 60 minutes and wipe off before applying capsaicin to reduce application-related discomfort 1
Additional Options
Alpha Lipoic Acid (ALA)
- Recommended for management of neuropathic pain, particularly effective in diabetic neuropathy 1
- Growing evidence supports its use despite limited studies specifically in HIV-associated neuropathy 1
Medical Cannabis
- May be considered in appropriate patients (weak recommendation) 1
- More effective in patients with prior cannabis use
- Balance potential benefits against risks of neuropsychiatric effects, lung damage, and addiction 1
Treatment Algorithm
First attempt: Pregabalin (most similar to gabapentin but better pharmacokinetics)
- If effective but side effects occur: Try lower dose or divided dosing
- If ineffective or intolerable: Move to step 2
Second attempt: SNRIs (duloxetine or venlafaxine)
- Particularly good choice if patient also has depression or anxiety
- If ineffective or intolerable: Move to step 3
Third attempt: TCAs (amitriptyline or imipramine)
- Use with caution in elderly or those with cardiovascular disease
- If ineffective or intolerable: Move to step 4
Fourth attempt: Topical capsaicin
- Good option for localized neuropathic pain
- If ineffective or intolerable: Move to step 5
Fifth attempt: Alpha lipoic acid
- Consider particularly for diabetic neuropathy
- If ineffective: Consider combination therapy or specialist referral
Important Considerations
- Renal function: Both pregabalin and gabapentin require dose adjustment in renal impairment 2
- Titration: Start at low doses and titrate gradually to minimize side effects
- Withdrawal: Taper gradually when discontinuing to avoid withdrawal symptoms 2
- Monitoring: Assess efficacy after 3-8 weeks of titration plus 2 weeks at maximum dose 2
- Avoid: Lamotrigine is not recommended for HIV-associated neuropathic pain 1
Non-Pharmacological Options
Consider adding these approaches alongside medication: