Guidelines for Pregabalin Use in Neuropathic Pain and Epilepsy
Pregabalin is recommended as a first-line treatment for neuropathic pain at doses of 150-600 mg/day in divided doses, with efficacy demonstrated in postherpetic neuralgia, diabetic peripheral neuropathy, and neuropathic pain associated with spinal cord injury. 1
Dosing and Titration for Neuropathic Pain
- Starting dose: 50 mg three times daily or 75 mg twice daily 2, 1
- Titration: Increase to 300 mg/day after 3-7 days, then by 150 mg/day every 3-7 days as tolerated 2
- Maximum dose: 600 mg/day (200 mg three times daily or 300 mg twice daily) 2
- Duration for adequate trial: 4 weeks 2
Pregabalin demonstrates a dose-response relationship, with higher doses providing greater pain relief. For postherpetic neuralgia, the NNT is 3.9 for at least 30% pain reduction at 300 mg/day and 2.7 at 600 mg/day 3. For diabetic peripheral neuropathy, the NNT is 22 at 300 mg/day and 9.6 at 600 mg/day 3.
Dosing for Epilepsy
- FDA-approved as adjunctive therapy for partial-onset seizures in patients 1 month of age and older 1
- For adults with epilepsy, start at 75 mg twice daily or 50 mg three times daily, with titration up to 600 mg/day based on response and tolerability 1
Renal Dose Adjustments
Pregabalin is primarily eliminated by renal excretion, requiring dose adjustment in renal impairment 1:
| Creatinine Clearance (mL/min) | Total Daily Dose Range (mg/day) | Dose Regimen |
|---|---|---|
| ≥60 | 150-600 | 2-3 divided doses |
| 30-59 | 75-300 | 2-3 divided doses |
| 15-29 | 25-150 | 1-2 divided doses |
| <15 | 25-75 | Single daily dose |
Comparative Efficacy
- Pregabalin has similar efficacy to gabapentin for neuropathic pain but with more straightforward pharmacokinetics and dosing 2, 4
- In diabetic neuropathy, duloxetine (60-120 mg/day) is an alternative with NNT of 5.2 for 60 mg/day 2
- For postherpetic neuralgia, pregabalin is more effective than placebo, with 50% of patients achieving at least 30% pain reduction at 300 mg/day versus 25% with placebo 3
Adverse Effects
The most common adverse effects include:
- Dizziness (29% at 300 mg/day, 35% at 600 mg/day) 3
- Somnolence (16% at 300 mg/day, 25% at 600 mg/day) 3
- Peripheral edema 2
- Weight gain 2, 5
These side effects can be minimized by:
- Starting at lower doses and titrating slowly 2
- Using divided doses (BID or TID) 2
- Taking particular care in elderly patients 4
Special Populations
- Elderly patients: Start with lower doses and titrate more slowly; increased risk of dizziness, somnolence, and confusion 1
- Pregnancy: Pregabalin may harm the unborn baby; women of reproductive potential should use effective contraception 1
- Breastfeeding: Pregabalin passes into breast milk; breastfeeding is not recommended 1
Abuse Potential
Pregabalin is classified as a Schedule V controlled substance due to its potential for abuse and dependence 1, 6. Risk factors for use above recommended dosages include:
- Male gender
- Concurrent use of antipsychotics or benzodiazepines 7
When to Consider Alternative Treatments
Consider alternative treatments when:
- Inadequate response to maximum tolerated dose after 4 weeks 2
- Intolerable side effects
- Specific contraindications (severe renal impairment)
For neuropathic pain, alternatives include:
- Gabapentin (900-3600 mg/day) 2, 4
- Duloxetine (60-120 mg/day) 2
- Tricyclic antidepressants 2
- Topical lidocaine 5% patch (for localized pain) 2
- Capsaicin 8% patch 2
Monitoring
- Assess pain reduction and functional improvement
- Monitor for adverse effects, particularly dizziness and somnolence
- Evaluate renal function periodically
- Watch for signs of abuse or misuse, especially in at-risk patients
Pregabalin should not be discontinued abruptly; taper gradually over at least one week to minimize withdrawal symptoms 1.