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Gabapentin

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

Gabapentin is a structural analogue of the neurotransmitter gamma-aminobutyric acid (GABA) (1,2)

Gabapentin:

  • is licensed for add-on treatment of partial seizures with or without secondary generalisation
  • has no significant interactions with other drugs
  • is widely used in chronic pain conditions
  • has a short half-life and generally needs to be given three times daily
  • does cross the blood-brain barrier and its activities are believed not to be GABA-related
  • has a high volume of distribution, is not significantly protein-bound or metabolised, and does not induce or inhibit hepatic enzymes; thus, it has minimal-to-no known interactions with other antiepileptic drugs (AEDs)

The mechanism of action is unclear - it was designed as a GABA analogue but does not bind to GABA receptors (1); it may bind to calcium channels in the brain.

With respect to use as an add-on treatment for drug-resistant focal epilepsy a systematic review concluded that (2):

  • Gabapentin has efficacy as an add-on treatment in people with drug-resistant focal epilepsy, and seems to be fairly well-tolerated.
    However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of gabapentin beyond a
    three-month period
  • in the systematic review "drug resistant focal epilepsy" was defined as:
    • if patients had focal-onset seizures (simple focal or complex focal or secondary generalised tonic-clonic seizures, or a combination of these) and failed to respond to at least one monotherapy AED

Advice for healthcare professionals (3):

 

  • to reflect growing concern about abuse, both pregabalin and gabapentin are now classified as Class C controlled substances (under the Misuse of Drugs Act 1971) and scheduled under the Misuse of Drugs Regulations 2001 (as amended) as Schedule 3, but are exempt from the safe custody requirements (see new legal requirements and resources for prescribers and dispensers below)

 

  • evaluate patients carefully for a history of drug abuse and dependence before prescribing pregabalin and gabapentin

 

  • observe patients on pregabalin and gabapentin for possible signs of abuse and dependence, for example, drug-seeking behaviour, dose escalation, and development of tolerance

 

  • ensure patients are aware of the risk of potentially fatal interactions with other medicines that cause CNS depression, particularly opioid medicines, and with alcohol

 

  • report suspected adverse drug reactions to pregabalin and gabapentin on a Yellow Card, including cases of abuse and dependence

 

The summary of product characteristics should be consulted before prescribing this drug.

Reference:

  • (1) Prescriber (2000), 11 (23), 45-55.
  • (2) Panebiancol M et al. Gabapentin add-on treatment for drug-resistant focal epilepsy. Cochrane Database of Systematic Reviews 2021, Issue 1. Art. No.: CD001415. DOI: 10.1002/14651858.CD001415.pub4.
  • (3) Pregabalin (Lyrica), gabapentin (Neurontin) and risk of abuse and dependence: new scheduling requirements from 1 April Drug Safety Update volume 12, issue 9: April 2019: 4.

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