Gabapentin (Neurontin)

Primer

Gabapentin (Trade name: Neurontin) is an anticonvulsant. It is commonly also used off-label for anxiety disorders, restless leg syndrome, and in alcohol use disorder. It is structurally similar to GABA but does not directly bind to GABA receptors.

Pharmacokinetics

See also article: Introduction to Pharmacology

Pharmacokinetics of Gabapentin

Absorption	Bioavailabiltiy of 59%. Tmax = 2-4 hours
Distribution	High volume of distribution (58L), less than 3% of gabapentin is bound to plasma proteins
Metabolism	Not metabolized to a significant extent in humans.
Elimination	Solely renal excretion as unchanged drug, and can be removed from plasma by hemodialysis.
Half-life	5-7 hours

See also article: Cytochrome (CYP) P450 Metabolism

Gabapentin: Cytochrome P450 Metabolism

Substrate of (Metabolized by)	Not metabolized in humans
Induces	-
Inhibits	-

Pharmacodynamics

Mechanism of Action

Gabapentin is designed as GABA analog (similar to pregabalin), which means it binds to the α2δ (alpha-2-delta) subunit of presynaptic voltage-sensitive Ca2+ channels (VSCCs), and block the release of excitatory neurotransmitters such as glutamate.
This changes the VSCC conformation to reduce calcium influx and thus reduce excessive stimulation of postsynaptic receptors.

Toxicity

Indications

Seizure disorders
Alcohol use disorder
Anxiety disorders, sleep disorders, pain syndromes

Dosing

Dosing for Gabapentin

Starting
Titration
Maximum
Taper

Formulations

Gabapentin comes in oral formulation.

Monitoring

Contraindications

Absolute

Relative

Drug-Drug Interactions

Side Effects

Gabapentin can also cause myoclonus (especially in the setting of acute kidney injuries when gabapentin is not able to be cleared).^[1]

Adverse Events

Withdrawal

Withdrawal may occur after prolonged use of gabapentin

Misuse

Gabapentin is an approved treatment as an adjunctive therapy in the management of epilepsy. However, it is most commonly prescribed off-label for other conditions, including anxiety, alcohol use disorder, and chronic pain.^[2]
Gabapentin misuse is increasing (oral, intranasal, and intravenous). Misuse can produce anxiolytic effects and a euphoria that is similar opioid misuse. Gabapentin can cause respiratory depression, physiologic dependence, and withdrawal symptoms on cessation (including diaphoresis, anxiety, confusion, and seizures).
- Patients who are co-prescribed gabapentin and opioids are at a significantly higher risk of death compared with those prescribed opioids alone.^[3]

Clinical Pearls

Special Populations

Geriatric

See main article: Geriatric Pharmacology

Pediatric

See main article: Pediatric Pharmacology

Obstetric and Fetal

See main article: Obstetric and Fetal Pharmacology

Medically Ill

See main article: Psychotropic Dosing in the Medically Ill

Resources

Research

¹⁾ Desai, A., Kherallah, Y., Szabo, C., & Marawar, R. (2019). Gabapentin or pregabalin induced myoclonus: A case series and literature review. Journal of Clinical Neuroscience, 61, 225-234.

²⁾ Smith, R. V., Havens, J. R., & Walsh, S. L. (2016). Gabapentin misuse, abuse and diversion: a systematic review. Addiction, 111(7), 1160-1174.

³⁾ Gomes, T., Juurlink, D. N., Antoniou, T., Mamdani, M. M., Paterson, J. M., & van den Brink, W. (2017). Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case–control study. PLoS medicine, 14(10), e1002396.

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