THERAPEUTICS

Brands

• Neurontin
• see index for additional brand names

Generic?

• Not in U.S. or Europe

Class

• Anticonvulsant, antineuralgic for chronic pain, alpha 2 delta ligand at voltage-sensitive calcium channels

Commonly Prescribed For

• (bold for FDA approved)
• Partial seizures with or without secondary generalization (adjunctive)
• Postherpetic neuralgia
• Neuropathic pain/chronic pain
• Anxiety (adjunctive)
• Bipolar disorder (adjunctive)

How The Drug Works

• Is a leucine analogue and is transported both into the blood from the gut and also across the blood-brain barrier into the brain from the blood by the system L transport system
• Binds to the alpha 2 delta subunit of voltage-sensitive calcium channels
• This closes N and P/Q presynaptic calcium channels, diminishing excessive neuronal activity and neurotransmitter release
• Although structurally related to gamma-aminobutyric acid (GABA), no known direct actions on GABA or its receptors

How Long Until It Works

• Should reduce seizures by 2 weeks
• Should also reduce pain in postherpetic neuralgia by 2 weeks; some patients respond earlier
• May reduce pain in other neuropathic pain syndromes within a few weeks
• If it is not reducing pain within 6–8 weeks, it may require a dosage increase or it may not work at all
• May reduce anxiety in a variety of disorders within a few weeks
• Not yet clear if it has mood stabilizing effects in bipolar disorder or antineuralgic actions in chronic neuropathic pain, but some patients may respond and if so, would be expected to show clinical effects starting by 2 weeks although it may take several weeks to months to optimize

If It Works

• The goal of treatment is complete remission of symptoms (e.g., seizures)
• The goal of treatment of chronic neuropathic pain is to reduce symptoms as much as possible, especially in combination with other treatments
• Treatment of chronic neuropathic pain most often reduces but does not eliminate symptoms and is not a cure since symptoms usually recur after medicine stopped
• Continue treatment until all symptoms are gone or until improvement is stable and then continue treating indefinitely as long as improvement persists

If It Doesn’t Work (for neuropathic pain or bipolar disorder)

• May only be effective in a subset of bipolar patients, in some patients who fail to respond to other mood stabilizers, or it may not work at all
• Many patients only have a partial response where some symptoms are improved but others persist or continue to wax and wane without stabilization of pain or mood
• Other patients may be nonresponders, sometimes called treatment-resistant or treatment-refractory
• Consider increasing dose, switching to another agent or adding an appropriate augmenting agent
• Consider biofeedback or hypnosis for pain
• Consider the presence of noncompliance and counsel patient
• Switch to another agent with fewer side effects
• Consider evaluation for another diagnosis or for a comorbid condition (e.g., medical illness, substance abuse, etc.)

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Gabapentin is itself an augmenting agent to numerous other anticonvulsants in treating epilepsy; and to lithium, atypical antipsychotics and other anticonvulsants in the treatment of bipolar disorder
• For postherpetic neuralgia, gabapentin can decrease concomitant opiate use
• For neuropathic pain, gabapentin can augment tricyclic antidepressants and SNRIs as well as tiagabine, other anticonvulsants and even opiates if done by experts while carefully monitoring in difficult cases
• For anxiety, gabapentin is a second-line treatment to augment SSRIs, SNRIs, or benzodiazepines

Tests

• None for healthy individuals
• False positive readings with the Ames N-Multistix SG¯ dipstick test for urinary protein have been reported when gabapentin was administered with other anticonvulsants