Gabapentin (Neurontin®) versus Pregabalin (Lyrica®)

Based on "Essential Psychopharmacology"
written by Stephen M. Stahl, MD, PhD

Pregabalin advantages over Gabapentin

  • As an antiepileptic, pregabalin may be more effective than gabapentin in reducing the seizure frequency4.
  • 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 gabapentin5.
  • Pregabalin has several superior pharmacodynamic characteristics3.
  • Pregabalin has a much higher bioavailability (90% versus 33-66%) and is rapidly absorbed (peak: 1 hour).
  • 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.
  • Pregabalin has faster onset of action and greater potency.

Gabapentin advantages over Pregabalin

  • Gabapentin is less addictive than pregabalin10. Unlike pregabalin, gabapentin is not scheduled as a controlled substance.
  • Gabapentin is not associated with peripheral edema9.
  • Gabapentin is more effective in controlling pain in patients with painful bladder syndrome14.

Difference between Gabapentin and Pregabalin

In the chart the distinctive features are marked:

Brand names
Neurontin® Lyrica®
Drug class
Lipophilic analogs of the inhibitory neurotransmitter GABA
Legal status
Non-controlled • Schedule V controlled substance
Proven potential for abuse and dependence
FDA-approved indications
• Post-herpetic neuralgia
• Epilepsy in adults
• Epilepsy in children age 3-12 years • Fibromyalgia
• Painful diabetic peripheral neuropathy
• Neuropathic pain associated with spinal cord injury
"Off-label" uses
• Postoperative pain
• Restless legs syndrome11
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.
Onset of action
~1-3 h ~25 min
5 to 7 hours 6 hours,
more prolonged duration of action
Oral bioavailability
33% 90%
Absorbed more slowly and variably4 Absorbed more rapidly4
Dose-response relationship
requires disproportionately higher dose increase to achieve higher plasma concentrations
more predictable dose-effect relationship
Drug interactions
• Not metabolized by CYP enzymes
Inexpensive More expensive
Pregabalin therapy may reduce the overall medical costs by lowering the need for concomitant medications and lessening primary care doctor visits8.

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 properties2:

  • Antiepileptic
  • Analgesic
  • Antineuropathic
  • Anxiolytic-like action
  • Lack of drug interactions
  • Minimal metabolism
  • Renal elimination.


Neuropathic pain

Pregabalin and gabapentin are used as first-line medications for nerve pain.

  • Postherpetic neuralgia (pain from shingles). Both drugs are licensed for postherpetic neuralgia.
  • Painful diabetic neuropathy. Current practice guidelines recommend pregabalin as the first-line medication13. Although gabapentin is not officially licensed for painful diabetic neuropathy, it is also recommended as the initial treatment.

Postoperative pain

Both gabapentinoids are effective for postoperative pain. Pregabalin may decrease pain better 7, 12.

Results of comparative study of gabapentin and pregabalin for postoperative analgesia6 Gabapentin Pregabalin
Postoperative pain scores   Lower score
Duration of analgesia   Longer
Postoperative requirements of analgesics   Less

Results of comparison of analgesic benefits of gabapentin vs pregabalin for postoperative analgesia7 Gabapentin Pregabalin
Single preoperative dose 1.5 hours before surgery 1200 mg 300 mg
The mean time of first epidural top-up/pain-free interval 7.23 h 14.80 h
Mean number of epidural top-ups 2.43 0.77
Preoperative dose of pregabalin 300 mg is superior to gabapentin 1200 mg in prolonging postoperative pain-free period in patients undergoing lower limb orthopedic surgery.

Combined use of Gabapentin and Pregabalin

Can you take gabapentin and pregabalin together?
As pregabalin and gabapentin have a similar mechanism of action and therapeutic effects, it makes no reason to take pregabalin concomitantly with gabapentin.

Further reading


  • 1. 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
  • 2. 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
  • 3. 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
  • 4. 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
  • 5. Toth C. Substitution of gabapentin therapy with pregabalin therapy in neuropathic pain due to peripheral neuropathy. Pain Med. 2010 Mar;11(3):456-65
  • 6. Mishra R, Tripathi M, Chandola HC. Comparative clinical study of gabapentin and pregabalin for postoperative analgesia in laparoscopic cholecystectomy. Anesth Essays Res. 2016 May-Aug;10(2):201-6. PubMed
  • 7. Khetarpal R, Kataria AP, Bajaj S, Kaur H, Singh S. Gabapentin vs pregabalin as a premedication in lower limb orthopaedics surgery under combined spinal epidural technique. Anesth Essays Res. 2016 May-Aug;10(2):262-7. PubMed
  • 8. Sicras-Mainar A, Rejas-Gutiérrez J, Perez-Paramo M, Navarro-Artieda R. Cost of treating peripheral neuropathic pain with pregabalin or gabapentin at therapeutic doses in routine practice. J Comp Eff Res. 2018 Jul;7(7):615-625. PubMed
  • 9. Ho JM, Tricco AC, Perrier L, Chen M, Juurlink DN, Straus SE. Risk of heart failure and edema associated with the use of pregabalin. Syst Rev. 2013 May 4;2:25. PubMed
  • 10. Bonnet U, Scherbaum N. How addictive are gabapentin and pregabalin? A systematic review. Eur Neuropsychopharmacol. 2017 Oct 5.
  • 11. Iftikhar IH, Alghothani L, Trotti LM. Gabapentin enacarbil, pregabalin and rotigotine are equally effective in restless legs syndrome: a comparative meta-analysis. Eur J Neurol. 2017 Sep 9. PubMed
  • 12. Eidy M, Fazel MR, Abdolrahimzadeh H, et al. Effects of pregabalin and gabapentin on postoperative pain and opioid consumption after laparoscopic cholecystectomy. Korean J Anesthesiol. 2017 Aug;70(4):434-438.
  • 13. Snyder MJ, Gibbs LM, Lindsay TJ. Treating Painful Diabetic Peripheral Neuropathy: An Update. Am Fam Physician. 2016 Aug 1;94(3):227-34. Available at American Academy of Family Physician
  • 14. Agarwal MM, Elsi Sy M. Gabapentenoids in pain management in urological chronic pelvic pain syndrome: Gabapentin or pregabalin? Neurourol Urodyn. 2017 Nov;36(8):2028-2033.

Originally published: July 12, 2016
Last updated: August 14, 2018


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