Background: Gabapentin (Neurontin) is an antiepileptic that has FDA indication to treat postherpetic neuralgia and partial onset seizures. This Fast Fact will review gabapentin’s role in neuropathic pain. See Fast Fact #289 for a comparison of gabapentin with pregabalin, a similar neuropathic analgesic.

Pharmacology: Structurally, it is like GABA, a primary inhibitory neurotransmitter, which means it decreases stimulation of nerve cells in the brain. Even though it does not directly bind to GABA receptors, calcium channel activation likely plays a role in its mechanism to curb neuropathic pain by reducing the release of excitatory neurotransmitters, which in turn allows for greater inhibitory effects of GABA.

Research data: 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). 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. 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.

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 1200-3600 mg, administered in three divided doses per day. Titration should proceed more slowly in older adults. 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 5 mg/kg/day with a usual dosage range of 8 to 35 mg/kg/day divided into 3 daily doses.

Dosing in renal impairment: Gabapentin doses must be reduced for patients with renal insufficiency.

• Creatinine Clearance (CrCl) 50-79 ml/min: maximum daily dose is 1800 mg given in 3 divided doses.
• CrCl 30-49 ml/min: maximum daily dose 900 mg in 2-3 divided doses
• CrCl 15-29 ml/min: maximum daily dose is 600 mg, in 1-2 divided doses.
• CrCl < 15 ml/min: maximum daily dose 300 mg given once daily; doses should decrease proportionally (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 (e.g., 100-300 mg).

Adverse drug reactions and cautions: Sedation, confusion, dizziness, ataxia, and peripheral edema 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. The FDA released a warning about gabapentin increasing the risk of breathing difficulties in patients with underlying lung disease or who are taking other CNS depressants (e.g., benzodiazepines, opioids). It is not a federally controlled substance, but considering the risk when prescribed with CNS depressants, some states classify it as a controlled V substance.

Cost: Gabapentin is available in 100 mg, 300 mg, and 400 mg capsules, 600 and 800 mg tablets, and as a liquid (250 mg/5 mL). Generic gabapentin is available and covered by most major insurance plans. Cost varies based on formulation, dose, etc, but prices for a monthly supply can range as low as $10-30.

Other palliative 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, sundowning behaviors, 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: After careful consideration of side effects, gabapentin can be a helpful adjuvant analgesic for neuropathic pain.

References

1. Wiffen PJ, Derry S, Bell RF, Rice ASC, Tölle TR, Phillips T, Moore RA. Gabapentin for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews 2017, Issue 6. Art. No.: CD007938. DOI: 10.1002/14651858.CD007938.pub4.
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 201;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.
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6. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162-173. doi:10.1016/S1474-4422(14)70251-0.
7. U.S. Food and Drug Administration. FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR). Available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin Last accessed November 27, 2024.
8. Gomes T, Juurlink DN, Antoniou T, et al. Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study. PLoS Med. 2017 Oct 3;14(10):e1002396. doi: 10.1371/journal.pmed.1002396. PMID: 28972983; PMCID: PMC5626029.
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Version History: This Fast Fact was originally edited by David E Weissman MD. 2nd Edition in May 2015. 3rd Edition in June 2021; 4th Edition in December 2024.
Conflicts of Interest: none to report.