Introduction   Gabapentin (Neurontin) has FDA indication to treat postherpetic neuralgia and partial onset seizures.  Controlled clinical trials in diabetic neuropathy and postherpetic neuralgia show that gabapentin at 2400-3600 mg/day has a similar efficacy to tricyclic antidepressants and carbamazepine.  Consistent, though less compelling clinical evidence supports its use for neuropathic cancer pain, pain associated with HIV infection, chronic back pain and others (readers wanting more in depth research findings are urged to consult Reference 1).  Due to this emerging evidence, it is widely used for the treatment of neuropathic pain.  The exact mechanism and site of action of gabapentin is unknown.   Gabapentin is generally well-tolerated, easily titrated, has few drug interactions, and does not require laboratory monitoring.  However, cost may be a limiting factor for some patients.  Patients suitable for gabapentin should have a clear neuropathic pain syndrome, characterized by sharp, shooting, lancinating and/or burning pain, in a nerve root (radicular) or stocking/glove distribution. See Fast Fact #289 for a comparison of gabapentin with pregabalin a similar neuropathic analgesic.

Adult Dosing    Gabapentin is started at low doses (100 mg to 300 mg total daily) and increased by 100 – 300 mg every 1-3 days to effect.  A typical schedule might be: day 1-2: 300 mg nightly; day 3-4: 300 mg twice daily; day 5-7: 600 mg twice daily; day 8 onwards: 600 mg three times a day.  The usual effective total daily dose is 900-3600 mg, administered in three divided doses per day.  Titration should proceed more slowly in elderly patients. If gabapentin is discontinued, it should be done over a minimum of a week to prevent withdrawal seizures.

Pediatric Use    There is limited data available assessing its effectiveness in neuropathic pain in children. The American Pain Society recommends that gabapentin be considered for pediatric neuropathic pain especially when concurrent analgesics are found to be too sedating.  Their recommended initial dose is 2 mg/kg/day with a usual dosage range of 8 to 35 mg/kg/day divided into 3 daily doses.

Dosing in Renal Failure   Gabapentin doses must be reduced for patients with renal insufficiency. 

• Creatinine Clearance (CrCl) 30-60 ml/min: maximum daily dose is 1400 mg, divided.
• CrCl 16-30 ml/min: maximum daily dose is 700 mg, given once daily.
• CrCl 15ml/min: maximum daily dose is 300 mg, once daily.  Doses should decrease proportionally for CrCl less than 15 ml/min (e.g. 300 mg every other day for a CrCl of ~7.5 ml/min).
• For patients on hemodialysis a supplemental dose is usually given after dialysis (usually 100-300 mg).

Adverse Reactions    Sedation, confusion, dizziness, and ataxia are the most common side effects, especially with rapid dose titration.  Tolerance to these effects appears to develop within a few days if the dose is held at the highest tolerated dose until symptoms improve or stabilize.

Dosage Formulations    Gabapentin is available in 100 mg, 300 mg, and 400 mg capsules, 600 mg and 800 mg tablets, and as a liquid (250mg/5mL).

Cost    Gabapentin is more expensive than older agents used for neuropathic pain (tricyclic antidepressants and older anti-epileptic drugs such as carbamazepine).  Generic gabapentin is available, although can cost ~$100 for 90 600 mg tablets.

Other Palliative Care Uses of Gabapentin    Small scale published trials have shown efficacy in the treatment of severe chronic hiccups, pruritus, postoperative pain and delirium, restless leg syndrome and hot flashes. Perhaps more compelling is its potential efficacy for chronic cough for which a randomized double-blind placebo controlled trial demonstrated significant improvement in cough-specific quality of life, cough frequency, and cough severity. See Fast Fact #200.

Summary    Gabapentin is a safe and effective adjuvant analgesic for neuropathic pain.  Physicians should become comfortable using and titrating gabapentin in patients with neuropathic pain syndromes.

References

1. Moore R, Wiffen PJ, Derry S, Toelle T, Rice AS C. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No.: CD007938. DOI: 10.1002/14651858.CD007938.pub3
2. Mishra S, Bhatnagar S, et al.  A comparative efficacy of amitriptyline, gabapentin, and pregabalin in neuropathic cancer pain: a prospective randomized double-blind placebo-controlled study. American Journal of Hospice and Palliative Medicine 2012;29:177-182.
3. Caraceni A, et al. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the gabapentin cancer pain study group. J Clin Onc. 2004; 22:2909-2917.
4. American Pain Society. Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain. 6th ed, Glenview, IL: American Pain Society, 2008.
5. Micromedex Drug Database. Thompson Reuters. http://www.micromedex.com.
6. Giampiero P, Aielli F, et al.  Gabapentin in the treatment of hiccups in patients with advanced cancer: a 5-year experience. Clin Neuropharm 2010; 33:179-180.
7. Anand S, Gabapentin for pruritus in palliative care. Am J of Hospice and Pall Med 2012; 30:192-196.
8. Dauri M, Faria S, Gatti A, et al. Gabapentin and Pregabalin for the Acute Post-operative Pain Management. A Systematic-Narrative Review of the Recent Clinical Evidences. Curr Drug Targets 2009, 10(8):716-33.
9. Leung JM, Sands LP, et al.  Pilot clinical trial of gabapentin to decrease postoperative delirium in older patients.  Neurology. 2006; 67:310-314.
10. Saletu M, Anderer P, Saletu-Zyhlarz GM, et al. Comparative Placebo-Controlled Polysomnographic and Psychometric Studies on the Acute Effects of Gabapentin Versus Ropinirole in Restless Legs Syndrome. J Neural Transm 2010, 117(4):463-73.
11. Butt DA, Lock M, Lewis JE, et al. Gabapentin for the Treatment of Menopausal Hot Flashes: A Randomized Controlled Trial. Menopause 2008; 15(2):310-8.

Version History:  This Fast Fact was originally edited by David E Weissman MD.   2nd Edition published August 2005; 3rd Edition May 2015. Version re-copy-edited April 2009; then again May 2015; renal dosing information adjusted to reflect current recommendations, and updated cost information added.