Neurontin: Clinical Uses and Adverse Effects

Neurontin Treats Seizures, Tremors, Pain and More


The drug Neurontin (gabapentin) has a curious (sordid?) history. This drug was originally created as an antispasmodic medication but found to have better antiseizure properties. Thus in 1993, Neurontin was first marketed by Warner-Lambert as an antiseizure medication.

As adjunctive treatment for seizures, Neurontin was projected only to bring in a mere $5oo million.  Seeing more potential in its off-label (non-FDA approved) uses including neuropathic pain, migraines and bipolar disorder, Warner-Lambert and Pfizer (which later acquired Warner-Lambert) promoted Neurontin for a variety of off-label uses.

According to court ruling, Warner-Lambert and Pfizer disseminated misleading information about the drug by deciding to withhold negative findings about the drug from public view. Consequently, Kaiser Foundation Health Plan sued Pfizer and won $142 million, which was upheld in federal appeals court in 2013.

Neurontin: Mechanism of Action

Gabapentin (Neurontin) is an amino acid analog of a neurotransmitter called GABA. We still are unsure of how exactly gabapentin works; however, we have a couple of hypotheses.

First, although structurally similar to GABA, gabapentin doesn't work on GABA receptors. Instead, gabapentin may affect the synaptic and presynaptic release of GABA.

Second, gabapentin is transported into the brain by the l-amino acid transporter. Once in the brain, both gabapentin and pregabalin (a nearly identical drug) bind to the α2δ subunit of voltage-gated Ca2+ channels. The main mechanism of gabapentin probably has something to do with decreasing Ca2+ entry.

In other words, gabapentin or Neurontin directly affects the brain synapses.

Neurontin: Clinical Uses

Despite the Kaiser court case ruling, many physicians continue to prescribe Neurontin for various off-label uses. Neurontin is usually taken as a pill or capsule at an initial dose of 300 mg a day. Dosage is then titrated upward toward a maximum dose of 1800 mg a day.

Here are some clinical uses of Neurontin:

  • epilepsy
  • generalized tonic-clonic seizures
  • partial seizures
  • postherpetic neuralgia
  • neuropathic pain
  • fibromyalgia
  • generalized anxiety disorder
  • diabetic neuropathy
  • essential tremor
  • hot flashes

Of note, if Neurontin is taken for seizure disorder, seizure history must be recorded and monitored by a physician.

Neurontin: Adverse Effects

In addition to its low price--pregabalin is more expensive--probably one of the reasons that many providers feel comfortable prescribing Neurontin for a variety of conditions is because it is pretty safe with few serious adverse reactions.

Between 10 and 20 percent of all people taking Neurontin experience fatigue, dizziness or sleepiness.  Occasionally, gabapentin can cause neurological disturbance with seizure being a very serious and rare complication.

Neurontin passes through the body unmetabolized which explains why it has very few drug-drug interactions and doesn't interact with hepatic enzymes. In other words, gabapentin has very low protein binding and doesn't make it into circulation, instead crossing the blood-brain barrier and affecting the brain and spinal cord.

Neurontin can interfere with hydrocodone concentrations in the blood and thus dull the effects of opioids. If you take Neurontin and opioids for pain, you may need your medication dosages adjusted. On a similar note, people with renal failure may also need their Neurontin dosages adjusted (decreased).

If you or a loved one is taking Neurontin for pain, seizures or so forth, please don't drink alcohol, take illicit drugs or operate heavy machinery. Neurontin already exerts substantial effects on the nervous system, making intoxicants a bad idea.

Selected Sources

Mosby's Drug Reference for Health Professions, Second Edition, published in 2010 by Elsevier.

Porter RJ, Meldrum BS. Chapter 24. Antiseizure Drugs. In: Katzung BG, Masters SB, Trevor AJ. eds. Basic & Clinical Pharmacology, 12e. New York, NY: McGraw-Hill; 2012. Accessed April 21, 2015.

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