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Gabapentin (Neurontin) versus ...

Gabapentin vs. Pregabalin (Lyrica)

Difference between Gabapentin and Pregabalin chart (distinctive features are marked)

 
Gabapentin
(Neurontin)
Pregabalin
(Lyrica)
Drug class
Antiepileptic, GABA analogue
Mechanism of action Similar mechanism of action, but pregabalin has a stronger receptor binding affinity for the α2-δ protein subunit of voltage-gated calcium channels
Legal status Non-controlled Schedule V controlled substance
Proven potential for abuse and dependence
Common FDA approved indications
Post-herpetic neuralgia
Epilepsy in adults
Other FDA-approved indications Epilepsy in children age 3-12 years Fibromyalgia,
Painful diabetic peripheral neuropathy,
Neuropathic pain associated with spinal cord Injury
Bioavailability
33%
90%
Half-life
5 to 7 hours
6 hours,
more prolonged duration of action
Dose-response relationship
Non-linear,
requires disproportionately larger dose increase to achieve higher plasma concentrations
Linear,
more predictable dose-effect relationship
Pain relieving potency   pregabalin is 5 times more potent than gabapentin 11

Gabapentin and pregabalin are structurally and pharmacologically related compounds. Pregabalin is the pharmacologically active S-enantiomer of a gamma-amino acid analogue. Both anticonvulsants share many similar properties17 -- antiepileptic, analgesic, antineuropathic, and anxiolytic-like action; lack of drug interactions; minimal metabolism; renal elimination.

Pregabalin has several superior pharmacodynamic characteristics15. Pregabalin has a much higher bioavailability (90% versus 33-66%) and is rapidly absorbed (peak: 1 hour). Also, plasma concentrations increase linearly with increasing dose. Gabapentin is slowly absorbed (peak: 3 to 4 hours) and plasma concentrations have a non-linear relationship to increasing doses.

As an antiepileptic, pregabalin 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 has shown that pregabalin can provide additional relief and improvement in quality of life in those who did not respond to gabapentin14.

Combined use of gabapentin and pregabalin
As pregabalin and gabapentin have a similar mechanism of action and properties, it makes no reason to take pregabalin concomitantly with gabapentin.

Gabapentin vs. Amitriptyline

Painful diabetic neuropathy
In the study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain, moderate or greater pain relief was experienced in 52% of patients with gabapentin and 67% of patients with amitriptyline. Study concluded that gabapentin does not appear to offer considerable advantage over amitriptyline and is more expensive 4.

Earlier study has shown that gabapentin produces greater improvements than amitriptyline in pain and paresthesia associated with diabetic neuropathy 2.

Chronic pelvic pain
Gabapentin alone or in combination with amitriptyline is superior to amitriptyline alone in the treatment of female chronic pelvic pain 3.

Peripheral neuropathic pain
In the double blind randomized trial both gabapentin and amitriptyline were effective for the management of peripheral neuropathic pain. However, improvement in shooting pain and patient satisfaction were significantly higher with gabapentin treatment. Also gabapentin was more effective in paroxysmal shooting pain than in other pain qualities 6.

Safety & Side effects
Gabapentin is better tolerated than amitriptyline. Side effects occur more frequently with amitriptyline than with gabapentin 2, 3, 6.

Gabapentin has no significant drug interactions while amitriptyline has several clinically significant drug interactions (e.g. MAOI, cisapride, thyroid agents).

Gabapentin is more costly than amitriptyline and requires frequent dosing regimen.

Gabapentin vs. Lamotrigine (Lamictal)

Partial epilepsy:
Unblinded randomised controlled trial has shown that lamotrigine is significantly better than gabapentin in the treatment of partial onset seizures 1.

Epilepsy:
Gabapentin and lamotrigine are similarly effective and well tolerated in patients with newly diagnosed epilepsy 5 and elderly patients with epilepsy 18.

Results of randomised, double-blind study comparing gabapentin versus lamotrigine in newly diagnosed epilepsy 5
Gabapentin
Lamotrigine
Regimen 1,200 - 3,600 mg/day for 24 weeks 100 - 300 mg/day for 24 weeks
Exit event, number of patients
19 of 148 patients
19 of 143 patients
Median time to exit
69 days
48 days
Number of patients remained seizure free during the final 12 weeks of treatment
80 of 106 patients
(75.5%)
73 of 96 patients
(76.0%)
Number of patients withdrew form treatment because of drug-related adverse events
14 of 106 patients
(8.9%)
15 of 96 patients
(9.9%)

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%.

Gabapentin vs. Carbamazepine (Tegretol)

Epilepsy:

Unblinded randomised controlled trial has shown that carbamazepine is significantly better than gabapentin for patients with partial onset seizures 1.

Side effects and tolerability: Gabapentin is better tolerated and produces significantly fewer untoward cognitive effects compared with carbamazepine 8, 18.

Gabapentin vs. Phenobarbital

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 vs. Topiramate (Topamax)

Side effects: Gabapentin is better tolerated than topiramate16. Weight loss and numbness are common with topiramate. Dizziness, weight gain and somnolence are more common with gabapentin.

Unlike gabapentin, topiramate has demonstrated risk of teratogenicity9.

Topiramate has prominent negative effects on cognition, whereas gabapentin has only minimal impact on cognitive abilities 6.

Migraine prophylaxis:
Both drugs are effective in migraine prophylaxis. Topiramate works slightly more efficaciously than gabapentin.

Results of comparative randomized open label control trial of topiramate and gabapentin in migraine prophylaxis16
Gabapentin
Topiramate
Reduction in mean monthly migraine frequency from 11.97 +/- 4.452 to 2.73 +/- 2.59 from 10.67 +/- 4.25 to 1.82 +/- 2.02
Reduction in severity from 6.93 +/- 1.90 to 1.18 +/- 1.01 from 6.60 +/- 2.122 to 1.03 +/- 0.92
Reduction in the average duration of attacks from 22.20 +/- 20.72 to 1.08 +/- 1.40 hours from 25.77 +/- 22.32 hours to 1.05 +/- 1.06 hours
Adverse effects dizziness,
weight gain,
somnolence
weight loss,
numbness
Further reading
References
  • 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. Salinsky MC, Storzbach D, Spencer DC, Oken BS, Landry T, Dodrill CB Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers. Neurology. 2005 Mar 8;64(5):792-8. 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. Holmes LB, Hernandez-Diaz S. Newer anticonvulsants: lamotrigine, topiramate and gabapentin. Birth Defects Res A Clin Mol Teratol. 2012 Aug;94(8):599-606. 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
  • 11. Shamsi Meymandi M, Keyhanfar F. Relative potency of pregabalin, gabapentin, and morphine in a mouse model of visceral pain. Can J Anaesth. 2013 Jan;60(1):44-9. PubMed
  • 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
  • 16. Zain S, Khan M, Alam R, Zafar I, Ahmed S. Comparison of efficacy and safety of topiramate with gabapentin in migraine prophylaxis: randomized open label control trial. J Pak Med Assoc. 2013 Jan;63(1):3-7.
  • 17. Brawek B, Löffler M, Weyerbrock A, Feuerstein TJ. Effects of gabapentin and pregabalin on K+-evoked 3H-GABA and 3H-glutamate release from human neocortical synaptosomes. Naunyn Schmiedebergs Arch Pharmacol. 2009 Apr;379(4):361-9. PubMed
  • 18. Rowan AJ, Ramsay RE, Collins JF, et al. New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology. 2005 Jun 14;64(11):1868-73. PubMed

Published: March 31, 2008
Last updated: July 15, 2014

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