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Gabapentin and pregabalin are structurally related compounds. But how do they compare?

As an antiepileptic, pregabalin (Lyrica) may be more effective than gabapentin in reducing the seizure frequency10.

In the treatment of neuropathic pain pregabalin has been shown in studies to provide equivalent efficacy to gabapentin, however, at much lower doses. The recent study of patients with neuropathic pain shows that pregabalin can provide additional relief and improvement in quality of life in those who did not respond to gabapentin14.

Part of the reason why pregabalin works better is that it has superior pharmacodynamic characteristics15. It has a much higher bioavailability (90% versus 33-66%) and is rapidly absorbed (peak: 1 hr). Also, plasma concentrations increase linearly with increasing dose. This is not true with gabapentin. Gabapentin is slowly absorbed (peak: 3 to 4 hours) and more importantly, plasma concentrations have a non-linear relationship to increasing doses.

• Efficacy:
• Painful diabetic neuropathy:
  In an open-label randomized trial gabapentin produced greater improvements than amitriptyline in pain and paresthesia associated with diabetic neuropathy 2.
  In randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy moderate or greater pain relief was experienced in 11 of 21 patients with gabapentin and 14 of 21 patients with amitriptyline 4.
• Peripheral neuropathic pain:
  In the double blind randomized trial gabapentin was compared in efficacy and safety with amitriptyline in neuropathic pain treatment 6. Both gabapentin and amitriptyline provided effective pain control. The degree of pain improvement and patient satisfaction scale were significantly higher with gabapentin. Also, gabapentin was more effective especially in paroxysmal shooting pain than other pain qualities.
  
• Chronic pelvic pain: Randomized controlled study have shown that gabapentin alone or in combination with amitriptyline is better than amitriptyline alone in the treatment of female chronic pelvic pain 3.
• Side effects and tolerability: Gabapentin appears to be better tolerated than amitriptyline. Side effects are more frequent with amitriptyline than with gabapentin 2.

• Efficacy:
• Post-herpetic neuralgia: Gabapentin and nortriptyline ware compared in a randomized trial in post-herpetic neuralgia (PHN). Gabapentin appears to be equally effective to nortriptyline 9.
• Side effects and tolerability: Gabapentin is better tolerated as compared to nortriptyline 9.

• Efficacy:
• Partial epilepsy:
  Unblinded randomised controlled trial have shown that lamotrigine is significantly better than carbamazepine for patients with partial onset seizures 1.
• Epilepsy:
  Gabapentin and lamotrigine are similarly effective and well tolerated in patients with newly diagnosed epilepsy 5.
• Mood disorders:
  Controlled comparative study evaluated the efficacy of lamotrigine and gabapentin monotherapy versus placebo in refractory bipolar and unipolar mood disorders 12. Response rates were the following: lamotrigine 52%; gabapentin 26%; placebo 23%.

• Efficacy:
• Partial epilepsy: Unblinded randomised controlled trial have shown that carbamazepine is significantly better than gabapentin for patients with partial onset seizures 1.
• Side effects and tolerability: Gabapentin produces significantly fewer untoward cognitive effects compared with carbamazepine 8.

• Efficacy:
• Smoking cessation:
  Gabapentin is less efficacious than bupropion for smoking cessation but is associated with fewer dropouts from side effects. The severity of physical discomfort is less with bupropion 7.

The small randomized, open-label study13 compared gabapentin with phenobarbital for reducing symptoms of alcohol withdrawal. In the study the proportion of patients needing “rescue” phenobarbital for breakthrough signs and symptoms of withdrawal did not significantly differ between treatment groups (57% of the gabapentin group vs. 38% of the phenobarbital group). The proportion of those who failed to complete the trial also did not significantly differ between the groups.

There were no significant differences in withdrawal symptoms or psychological distress, nor were there serious adverse events. These findings suggest that gabapentin may be as effective as phenobarbital in the treatment of alcohol withdrawal.

• Gabapentin (Neurontin) Facts

• 1. Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, Cramp C, Cockerell OC, Cooper PN, Doughty J, Eaton B, Gamble C, Goulding PJ, Howell SJ, Hughes A, Jackson M, Jacoby A, Kellett M, Lawson GR, et al; SANAD Study group. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007 Mar 24;369(9566):1000-15. PubMed
• 2. Dallocchio C, Buffa C, Mazzarello P, Chiroli S. Gabapentin vs. amitriptyline in painful diabetic neuropathy: an open-label pilot study. J Pain Symptom Manage. 2000 Oct;20(4):280-5. PubMed
• 3. Sator-Katzenschlager SM, Scharbert G, Kress HG, Frickey N, Ellend A, Gleiss A, Kozek-Langenecker SA. Chronic pelvic pain treated with gabapentin and amitriptyline: a randomized controlled pilot study. Wien Klin Wochenschr. 2005 Nov;117(21-22):761-8. PubMed
• 4. Morello CM, Leckband SG, Stoner CP, Moorhouse DF, Sahagian GA. Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain. Arch Intern Med. 1999 Sep 13;159(16):1931-7. PubMed
• 5. Brodie MJ, Chadwick DW, Anhut H, Otte A, Messmer SL, Maton S, Sauermann W, Murray G, Garofalo EA. Gabapentin versus lamotrigine monotherapy: a double-blind comparison in newly diagnosed epilepsy. Epilepsia. 2002 Sep;43(9):993-1000. PubMed
• 6. Keskinbora K, Pekel AF, Aydinli I. Comparison of efficacy of gabapentin and amitriptyline in the management of peripheral neuropathic pain. Agri. 2006 Apr;18(2):34-40. PubMed
• 7. White WD, Crockford D, Patten S, El-Guebaly N. A randomized, open-label pilot comparison of gabapentin and bupropion SR for smoking cessation. Nicotine Tob Res. 2005 Oct;7(5):809-13. PubMed
• 8. Meador KJ, Loring DW, Ray PG, Murro AM, King DW, Nichols ME, Deer EM, Goff WT. Differential cognitive effects of carbamazepine and gabapentin. Epilepsia. 1999 Sep;40(9):1279-85. PubMed
• 9. Chandra K, Shafiq N, Pandhi P, Gupta S, Malhotra S. Gabapentin versus nortriptyline in post-herpetic neuralgia patients: a randomized, double-blind clinical trial--the GONIP Trial. Int J Clin Pharmacol Ther. 2006 Aug;44(8):358-63. PubMed
• 10. Delahoy P, Thompson S, Marschner IC. Pregabalin versus gabapentin in partial epilepsy: a meta-analysis of dose-response relationships. BMC Neurol. 2010 Nov 1;10(1):104
• 12. Frye MA, Ketter TA, Kimbrell TA, Dunn RT, Speer AM, Osuch EA, Luckenbaugh DA, Cora-Ocatelli G, Leverich GS, Post RM. A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. J Clin Psychopharmacol. 2000 Dec;20(6):607-14. PubMed
• 13. 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.
• 14. Toth C. Substitution of gabapentin therapy with pregabalin therapy in neuropathic pain due to peripheral neuropathy. Pain Med. 2010 Mar;11(3):456-65
• 15. Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010 Oct 1;49(10):661-9 PubMed

Published: March 31, 2008
Last updated: April 25, 2011