Neurontin

• Generic name: Gabapentin
• Trade names: Neurontin
• Pharmacologic category: Anticonvulsant, antineuralgic
• FDA approved: December 30, 1993
• Manufacturer: Pfizer
• Habit forming? No

Neurontin is an antiepileptic drug (AED) with antineuralgic properties. It is indicated for the treatment of epilepsy (repeated seizures) and management of postherpetic neuralgia. It may be considered in a number of psychiatric, neurologic, and pain disorders.

The most prominent side effects of Neurontin include dizziness, drowsiness, fatigue, and peripheral edema (swelling of extremities) 13.

• Absorption: Bioavailability decreases as dose increases: bioavailability is approximately 60%, 47%, 34%, 33%, and 27% following 900, 1,200, 2,400, 3,600, and 4,800 mg per day, respectively. Food has only a slight effect on rate and extent of absorption.
• Metabolism: it is not noticeably metabolized in humans.
• Elimination half-life: 5-7 hours.
• Excretion: excreted unchanged in the kidney.

• lack of important drug interactions
• does not induce or inhibit liver enzymes
• low toxicity
• effective in some people with bipolar mood disorders that have not responded to lithium or other mood-stabilizers
• generic availability

• Short half-life which requires a three times daily regimen.
• Not as efficacious as other anticonvulsants14. In particular, Neurontin is not effective against primarily generalized seizures such as absences.
• Sedating effects13.

• Painful diabetic neuropathy 5
• Migraine prophylaxis 3
• Interstitial cystitis 4
• Hot flashes
• Partial seizures, monotherapy
• Essential tremor 6
• Bipolar disorder 11
• Restless leg syndrome 7
• Postoperative pain management 2, 15
• Posttraumatic stress disorder (PTSD) 8
• Alcohol withdrawal 9
• Chronic daily headache 12

Bipolar disorder
Neurontin may have a role as adjunctive agent in the treatment of bipolar disorder particularly when it is complicated by co-morbid anxiety disorder or substance abuse. Randomized clinical trial comparing the prophylactic efficacy of adjunctive gabapentin to placebo suggests that, despite lack of acute efficacy, treatment with gabapentin might provide some benefit on the long-term outcome of bipolar disorder 11.

Neurontin is usually very well tolerated and has no pharmacological interference with other mood stabilizers. However, in the placebo-controlled study Neurontin has not been found to be an effective adjunctive treatment for bipolar disorder 10. This drug failing to show clear antimanic efficacy in randomized trials.

Neuropathic pain occurs when nerve fibers are injured.
Multiple, large, high-quality studies have demonstrated the safety and efficacy of Neurontin in neuropathic pain. It alleviates pain by reducing hyperalgesia and allodynia. Also, Neurontin improves various quality of life measures.

The efficacy of gabapentin in diabetic neuropathy and postherpetic neuralgia is similar (though not superior) to tricyclic antidepressants and carbamazepine, but it may be better tolerated. Around 30% of people can expect to achieve more than 50% pain relief.

Post-operative pain
Neurontin may have a place in the treatment of postoperative pain 2, 15. It may reduce both postoperative pain intensity and opioid requirements. It reduces movement-evoked pain and this can lead to enhanced functional postoperative recovery.

High-quality studies have demonstrated opioid-sparing benefit of gabapentin following various surgical procedures. This allows noticeably reduce nausea and vomiting after surgery.

Gabapentin is structurally related to GABA (gamma-aminobutyric acid). However, it does not bind to GABAA or GABAB receptors, and it does not appear to influence synthesis or uptake of GABA. High affinity binding sites have been located throughout the brain; these sites correspond to the presence of voltage-gated calcium channels specifically possessing the alpha-2-delta-1 subunit. This channel appears to be located presynaptically, and may modulate the release of excitatory neurotransmitters which participate in epileptogenesis and nociception.

Neurontin should be tapered off gradually. Tapering is desirable even in people who don't have epilepsy, since abrupt discontinuation has been associated with seizures and development of a syndrome resembling alcohol or benzodiazepine withdrawal. Neurontin should be suddenly discontinued only when necessary because of serious side effects.

• Neurontin reviews, ratings on DrugLib.com
• Neurontin reviews - success rate on DailyStrength.org
• Neurontin ratings - recommended by 80% of reviewers on Psych Central
• User reviews for restless legs syndrome, insomnia, migraine, neuralgia on Drugs.com

• Gabapentin on Merck Manual Professional
• 1. Neurontin on RxList
• 2. Lichtinger A, Purcell TL, Schanzlin DJ, Chayet AS. Gabapentin for postoperative pain after photorefractive keratectomy. J Refract Surg. 2011 Feb 28:1-5. PubMed
• 3. Di Trapani G, Mei D, Marra C, Mazza S, Capuano A. Gabapentin in the prophylaxis of migraine. Clin Ter. 2000 May-Jun;151(3):145-8. PubMed
• 4. Sasaki K, Smith CP, Chuang YC, Lee JY, Kim JC, Chancellor MB. Tech Urol. 2001 Mar;7(1):47-9.
• 5. Backonja MM. Gabapentin monotherapy for the symptomatic treatment of painful neuropathy in diabetes mellitus. Epilepsia. 1999;40 Suppl 6:S57-9; discussion S73-4
• 6. Gironell A, Kulisevsky J, Barbanoj M, Lo'pez-Villegas D, Herna'ndez G, Pascual-Sedano B. Arch Neurol. 1999 Apr;56(4):475-80.
• 7. Garcia-Borreguero D, Larrosa O, de la Llave Y, Verger K, Masramon X, Hernandez G. Treatment of restless legs syndrome: a double-blind, cross-over study. Neurology. 2002 Nov 26;59(10):1573-9.
• 8. Hamner MB, Brodrick PS, Labbate LA. Gabapentin in PTSD: a retrospective, clinical series of adjunctive therapy. Ann Clin Psychiatry. 2001 Sep;13(3):141-6. PubMed
• 9. Mariani JJ, Rosenthal RN, Tross S, Singh P, Anand OP. A randomized, open-label, controlled trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal. Am J Addict. 2006 Jan-Feb;15(1):76-84.
• 10. Pande AC, Crockatt JG, Janney CA, Werth JL, Tsaroucha G. A placebo-controlled trial of adjunctive therapy. Gabapentin Bipolar Disorder Study Group. Bipolar Disord. 2000 Sep;2(3 Pt 2):249-55. PubMed
• 11. Vieta E, Manuel Goikolea J, Marti'nez-Ara'n A, Comes M, Verger K, Masramon X, Sanchez-Moreno J, Colom F. A double-blind, randomized, placebo-controlled, prophylaxis study of adjunctive neurontin for bipolar disorder. J Clin Psychiatry. 2006 Mar;67(3):473-7. PubMed
• 12. Spira PJ, Beran RG; Australian Chronic Daily Headache Group. Neurology. 2003 Dec 23;61(12):1753-9.
• 13. Parsons B, Tive L, Huang S. Pooled analysis of adverse events from three clinical trials in people with postherpetic neuralgia. Am J Geriatr Pharmacother. 2004 Sep;2(3):157-62. PubMed
• 14. Sethi A, Chandra D, Puri V, Mallika V. Neurol India. 2002 Sep;50(3):359-63. PubMed
• 15. Straube S, Derry S, Moore RA, Wiffen PJ, McQuay HJ. Cochrane Database Syst Rev. 2010 May 12;(5):CD008183

Last modified: July, 2011