Background for Fast Fact #289     Gabapentin (Neurontin®) and pregabalin (Lyrica®) share a similar mechanism of action; however, the compounds differ in their pharmacokinetic and pharmacodynamic characteristics. See Fast Fact #049 for more information regarding gabapentin and Fast Fact #299 for pregabalin. This Fast Fact will compare and contrast these two agents.

Pharmacokinetic profile comparison      The major pharmacokinetic difference between gabapentin and pregabalin is their absorption from the GI tract.  The absolute bioavailability of gabapentin drops from 60-33% as the dosage increases from 900-3600 mg/day (1), while pregabalin remains ≥90% irrespective of dosage. This suggests that dose escalations of gabapentin are accompanied by a therapeutic ceiling effect, although this has not been proven in studies.  Neither medication binds to plasma proteins, both undergo negligible metabolism, and both are renally excreted with terminal half-lives of 5-6 hours.  Overall, literature suggests that pregabalin has a small pharmacokinetic advantage over gabapentin, although there is little evidence-based literature to support its clinical superiority in patient care (2).

Pharmacodynamic profile comparison     The onset of pregabalin is approximately 25 minutes, compared to 1-3 hours for gabapentin. Equally important, pregabalin can be more rapidly titrated to an effective dose range than gabapentin (1-2 days for pregabalin versus approximately 9 days for gabapentin) (3).

Other differences    Research suggests a target dose of at least 900-3600mg/day (in divided doses) of gabapentin to maintain analgesia for persistent pain (4,5).  With pregabalin, it appears analgesia can be achieved and maintained at any dose (6).  The side effects of both drugs are dose dependent, reversible, and relatively similar in nature (e.g., dizziness and somnolence).  There is no significant difference in the number of drug interactions.  Gabapentin is not a controlled substance (federally, some states have begun to classify it as a Schedule V drug), while pregabalin is federally designated as a Schedule V drug. 

Use in palliative care    Gabapentin is FDA-approved for post-herpetic neuralgia, and adjunctive therapy in the treatment of partial onset of seizures, while pregabalin is approved for diabetic peripheral neuropathy, post-herpetic neuralgia, fibromyalgia, and neuropathic pain associated with spinal cord injury, as well as an adjunctive therapy for adult patients with partial onset seizures.  Research suggests the number need to treat (NNT; i.e. the number of patients needed to be treated for one patient to benefit) in diabetic neuropathy for pregabalin is 4 (for a 50% reduction at 600 mg/day); while gabapentin had only a small effect on pain reduction (therefore the NNT was not reported) (7).  In another review, a combined NNT was calculated for a variety of neuropathic pain conditions and found NNT for pregabalin was 7.7 and gabapentin was 6.3 (8). Although gabapentin is frequently given to patients with chemotherapy-induced peripheral neuropathy, few controlled trials have been conducted and investigations have shown conflicting results. There has been only one study comparing the efficacy of gabapentin and pregabalin in neuropathic cancer pain. In this double-blind, randomized, placebo-controlled trial, patients were given amitriptyline, gabapentin, pregabalin, or placebo. There were statistically lower VAS scores in the pregabalin group when compared to the others. The authors also noted a statistically and clinically significant morphine-sparing effect of pregabalin as well (9).  This single, mid-quality trial has not been replicated.

Cost     Pregabalin is approximately three times more expensive than gabapentin; both are available as generic medications.

Summary     Pregabalin has some pharmacokinetic advantages over gabapentin, but is much more costly. There are no clear data demonstrating improved clinical outcomes of one agent over the other.

References 

1. Twycross R, Wilcock A, Charlesworth S, et al. Palliativedrugs.com therapeutic highlights: gabapentin. Indian J Palliat Care. 2003;9(2):71-74. 
2. 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;49(10):661-9. 
3. McCaffery M, Pasero C, editors. Pain: clinical manual. 2nd ed. St Louis, (MO): Mosby; 1999. 
4. Backonja MM, Serra J. Pharmacologic management part 1: better-studied neuropathic pain diseases. Pain Med. 2004 Mar;5 Suppl 1:S28-47. 
5. Farrar JT, Portenoy RK. Neuropathic cancer pain: the role of adjuvant analgesics. Oncology (Williston Park). 2001 Nov;15(11):1435-42, 1445; discussion 1445, 1450-3.
6. Pasero C, McCaffery M. Pain assessment and pharmacological management 1e. St Louis, MO: Mosby; 1991.
7. Bril V, England J, Franklin GM, Backonja M, Cohen J, Del Toro D, Feldman E, Iverson DJ, Perkins B, Russell JW, Zochodne D; American Academy of Neurology; American Association of Neuromuscular and Electrodiagnostic Medicine; American Academy of Physical Medicine and Rehabilitation. Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011 May 17;76(20):1758-65.
8. 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.
9. Mishra S, Bhatnagar S, Goyal GN, Rana SP, Upadhya SP. A comparative efficacy of amitriptyline, gabapentin, and pregabalin in neuropathic cancer pain: a prospective randomized double-blind placebo-controlled study. Am J Hosp Palliat Care. 2012 May;29(3):177-82.

Authors’ Affiliations: University of Pittsburgh Medical Center, Pittsburgh, PA. UPMC Health System, Pittsburgh PA.
Conflict of Interest: The authors have disclosed no relevant conflicts of interest.
Version History: First published April 2015; reviewed and updated in December 2024 by Maria Lowry Pharm D.